Digital Commons Network^™

New Jersey’S Web-Based Parent-Engaged Developmental Monitoring Information: Mapping And Critical Appraisal, Danielle Catalano, Ms, Otr/L

Post-Professional Occupational Therapy Doctorate Culminating Presentations

Caregivers use web-based information to make decisions about their children’s health and development. Due to the state’s high prevalence of developmental delays, New Jersey has developed numerous web-based early childhood initiatives to promote parent engagement. However, the quality of those resources is unknown. This critical appraisal evaluated the quality, readability, and accessibility of New Jersey’s commonly used web-based information on parent-engaged developmental monitoring in children aged 0-3. A systematic web search yielded 112 results. Thirty-six webpages were reviewed by three independent reviewers using four standardized assessment tools. Reviewers found that most information was written at a twelfth-grade reading level, two …

Evaluating Hope: A Trauma-Informed Sensory Training For Early Childhood Educators, Andrea Houtras, Otd, Otr/L

Post-Professional Occupational Therapy Doctorate Culminating Presentations

Introduction: Adverse childhood experiences create challenges in sensory integration (Perry, 2006) impacting preschoolers’ participation and occupational performance (May-Benson, 2016). Professional development in trauma-informed sensory training is essential to support early childhood educators working with this population (Loomis, 2018; Perry, 2006).

Objectives: To develop a trauma-informed sensory training and evaluate its validity and usefulness for early childhood educators.

Methods: We used a modified Delphi method to evaluate the training’s adherence to Ayres Sensory Integration® and trauma-informed care principles of practice and usefulness for early childhood educators. A convenience sample of three expert groups reviewed the training and completed surveys to …

Utility Of T-Cell Immunosequencing In Distinguishing Mycosis Fungoides Progression From Treatment Related Cutaneous Adverse Events, Safiyyah Bhatti, Daniel Joffe, Lauren Banner, Sahithi Talasila, Jenna Mandel, Jason Lee, Pierluigi Porcu, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

Cutaneous adverse events of both topical and systemic drugs in patients with mycosis fungoides (MF) present a diagnostic challenge as it is often difficult to distinguish drug associated rash from disease progression in the skin. Mogamulizumab and mechlorethamine gel are approved treatments for MF, both of which can cause treatment related cutaneous adverse events. It can often be challenging to distinguish mogamulizumab associated rash (MAR) and mechlorethamine gel associated hypersensitivity dermatitis from MF progression both clinically and histologically. High-throughput sequencing (HTS) of the T-cell receptor (TCR), also known as immunosequencing, can be used to assess T-cell clonality to support a …

Drug-Free Noninvasive Thermal Nerve Block: Validation Of Sham Devices, Michael Fishman, Ahish Chitneni, Alaa Abd-Elsayed, Samuel Grodofsky, Ashley Scherer, Brendan Schetzner, Malvina Klusek, Stephen Popielarski, Stephen Meloni, Steven Falowski, Philip Kim, Konstantin Slavin, Stephen Silberstein

Department of Jefferson Headache Center Papers and Presentations

Headache is a leading cause of disability and suffering. One major challenge in developing device treatments is demonstrating their efficacy given devices' often-high placebo rate. This paper reviews the importance of validating sham devices as part of finalizing the design for larger-scale prospective randomized controlled trials in patients with chronic headache as well as the results of a prospective, single-blind trial to validate two potential sham noninvasive thermal nerve block devices. Study participants were trained to self-administer thermal nerve block treatment using sham devices in an office visit. Two different sham systems with different temperature profiles were assessed. Devices were …

Pkcε Activator Protects Hippocampal Microvascular Disruption And Memory Defect In 3×Tg-Alzheimer's Disease Mice With Cerebral Microinfarcts, Huaixing Wang, Zongxiu Zhang, Jarin Hongpaisan

Center for Translational Medicine Faculty Papers

BACKGROUND: Current evidence suggests that microvessel disease is involved in Alzheimer's disease (AD). Cerebrovascular disease correlates with cardiovascular disease and is complicated in ≈40% of AD patients. The protein kinase C (PKC) ε activator DCPLA can stimulate human antigen (Hu) R that prevents degradation and promotes the translation of mitochondrial Mn-superoxide dismutase (MnSOD) and vascular endothelial growth factor-A (VEGF) mRNAs.

METHODS: To induce brain microinfarcts, we injected triple transgenic (3×Tg) and wild-type (WT) control mice with microbeads (20 μm caliber) into common carotid arteries, with or without the DCPLA-ME (methyl-ester) for 2 weeks. After water maze training, mice at 16 …

Implementation Of Multipronged Approach In Patients With Chest Trauma Reduces Vap And Unplanned Admission To The Icu, Julie Donnelly, Msn, Rn, Trcn, Kristen Firely, Msn, Rn, Nicole Olszewski, Bsn, Rn, Jessica Byrne, Msn, Rn-Bc, Tiffani Stanley, Cstr, Joshua A. Marks, Md, Facs, Fccm, George Koenig

Department of Surgery Posters

Problem

The incidence of pulmonary complications in trauma patients with chest trauma has been reported to be as high as 49% (Ruibel L, 2022). However, all trauma patients are at risk for developing pulmonary complications due to a multitude of factors some pre-existing while others injury related sequela. Within our institution, we observed an increase in pulmonary complications through review of our TQIP (Spring 2020) and state registry data.

Iron Oxide-Coupled Crispr-Ncas9-Based Genome Editing Assessment In Mucopolysaccharidosis Iva Mice, Andrés Leal, Betul Celik, Nidhi Fnu, Shaukat Khan, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis (MPS) IVA is a lysosomal storage disorder caused by mutations in the GALNS gene that leads to the lysosomal accumulation of keratan sulfate (KS) and chondroitin 6-sulfate, causing skeletal dysplasia and cardiopulmonary complications. Current enzyme replacement therapy does not impact the bone manifestation of the disease, supporting that new therapeutic alternatives are required. We previously demonstrated the suitability of the CRISPR-nCas9 system to rescue the phenotype of human MPS IVA fibroblasts using iron oxide nanoparticles (IONPs) as non-viral vectors. Here, we have extended this strategy to an MPS IVA mouse model by inserting the human GALNS cDNA into the …

A Review Of Slipping Rib Syndrome: Diagnostic And Treatment Updates To A Rare And Challenging Problem, Isheeta Madeka, Sneha Alaparthi, Marisa Moreta, Shawn Peterson, Jeffrey Mojica, Johanes Roedl, Olugbenga Okusanya

Department of Surgery Faculty Papers

Slipping rib syndrome (SRS) is a disorder that occurs when one or more of the eighth through tenth ribs become abnormally mobile. SRS is a poorly understood condition leading to a significant delay in diagnosis and therapeutic management. History and a physical exam are usually sufficient for a diagnosis of SRS. The utility of dynamic ultrasounds has also been studied as a useful diagnostic tool. Multiple surgical techniques for SRS have been described within the literature. Cartilage rib excision (CRE) has been the most common technique utilized. However, the literature has shown a high rate of recurrence and associated risks …

Xtx101, A Tumor-Activated, Fc-Enhanced Anti-Ctla-4 Monoclonal Antibody, Demonstrates Tumor-Growth Inhibition And Tumor-Selective Pharmacodynamics In Mouse Models Of Cancer, Kurt A. Jenkins, Miso Park, Magali Pederzoli-Ribeil, Ugur Eskiocak, Parker Johnson, Wilson Guzman, Megan Mclaughlin, Deborah Moore-Lai, Caitlin O'Toole, Zhen Liu, Benjamin Nicholson, Veronica Flesch, Huawei Qiu, Tim Clackson, Ronan C. O'Hagan, Ulrich Rodeck, Margaret Karow, Jennifer O'Neil, John C. Williams

Department of Dermatology and Cutaneous Biology Faculty Papers

INTRODUCTION: The clinical benefit of the anti-CTLA-4 monoclonal antibody (mAb) ipilimumab has been well established but limited by immune-related adverse events, especially when ipilimumab is used in combination with anti-PD-(L)1 mAb therapy. To overcome these limitations, we have developed XTX101, a tumor-activated, Fc-enhanced anti-CTLA-4 mAb.

METHODS: XTX101 consists of an anti-human CTLA-4 mAb covalently linked to masking peptides that block the complementarity-determining regions, thereby minimizing the mAb binding to CTLA-4. The masking peptides are designed to be released by proteases that are typically dysregulated within the tumor microenvironment (TME), resulting in activation of XTX101 intratumorally. Mutations within the Fc region …

Evaluating The Efficacy Of A Thermoresponsive Hydrogel For Delivering Anti-Collagen Antibodies To Reduce Posttraumatic Scarring In Orthopedic Tissues., Andrzej Steplewski, Jolanta Fertala, Lan Cheng, Mark Wang, Michael Rivlin, Pedro K Beredjiklian, Andrzej Fertala

Department of Orthopaedic Surgery Faculty Papers

Excessive posttraumatic scarring in orthopedic tissues, such as joint capsules, ligaments, tendons, muscles, and peripheral nerves, presents a significant medical problem, resulting in pain, restricted joint mobility, and impaired musculoskeletal function. Current treatments for excessive scarring are often ineffective and require the surgical removal of fibrotic tissue, which can aggravate the problem. The primary component of orthopedic scars is collagen I-rich fibrils. Our research team has developed a monoclonal anti-collagen antibody (ACA) that alleviates posttraumatic scarring by inhibiting collagen fibril formation. We previously established the safety and efficacy of ACA in a rabbit-based arthrofibrosis model. In this study, we evaluate …

Master Transcription Factor Reprogramming Unleashes Selective Translation Promoting Castration Resistance And Immune Evasion In Lethal Prostate Cancer, Sandra Santasusagna, Shijia Zhu, Vijayakumar Jawalagatti, Marc Carceles-Cordon, Adam Ertel, Saioa Garcia-Longarte, Won-Min Song, Naoto Fujiwara, Peiyao Li, Isabel Mendizabal, Daniel P. Petrylak, William Kevin Kelly, E. Premkumar Reddy, Liguo Wang, Matthew J. Schiewer, Amaia Lujambio, Jeffrey Karnes, Karen E. Knudsen, Carlos Cordon-Cardo, Haidong Dong, Haojie Huang, Arkaitz Carracedo, Yujin Hoshida, Veronica Rodriguez-Bravo, Josep Domingo-Domenech

Department of Medical Oncology Faculty Papers

Signaling rewiring allows tumors to survive therapy. Here we show that the decrease of the master regulator microphthalmia transcription factor (MITF) in lethal prostate cancer unleashes eukaryotic initiation factor 3B (eIF3B)-dependent translation reprogramming of key mRNAs conferring resistance to androgen deprivation therapy (ADT) and promoting immune evasion. Mechanistically, MITF represses through direct promoter binding eIF3B, which in turn regulates the translation of specific mRNAs. Genome-wide eIF3B enhanced cross-linking immunoprecipitation sequencing (eCLIP-seq) showed specialized binding to a UC-rich motif present in subsets of 5' untranslated regions. Indeed, translation of the androgen receptor and major histocompatibility complex I (MHC-I) through this motif …

Interleukin 31 Receptor Α Promotes Smooth Muscle Cell Contraction And Airway Hyperresponsiveness In Asthma, Santhoshi Akkenepally, Dan Yombo, Sanjana Yerubandi, Geereddy Bhanuprakash Reddy, Deepak Deshpande, Francis Mccormack, Satish Madala

Center for Translational Medicine Faculty Papers

Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness (AHR), inflammation, and goblet cell hyperplasia. Multiple cytokines, including IFNγ, IL-4, and IL-13 are associated with asthma; however, the mechanisms underlying the effects of these cytokines remain unclear. Here, we report a significant increase in the expression of IL-31RA, but not its cognate ligand IL-31, in mouse models of allergic asthma. In support of this, IFNγ, IL-4, and IL-13 upregulated IL-31RA but not IL-31 in both human and mice primary airway smooth muscle cells (ASMC) isolated from the airways of murine and human lungs. Importantly, the loss of IL-31RA …

The Importance Of Triple Panel Testing For Hepatitis B And The Burden Of Isolated Anti-Hepatitis B Core Antibodies Within A Community Sample, Catherine Freeland, Vivek Sreepathi, Richard Hass, Jonathan Fenkel, Jessie Torgersen, Kenneth Rothstein, Chari Cohen, Robert Gish

College of Population Health Faculty Papers

Within the United States (US), 2.4 million individuals are living with chronic hepatitis B, but less than 20% are diagnosed. Isolated anti-hepatitis B core (iAHBc) antibodies indicate serology in an individual that is positive for anti-HBc antibodies, while negative for surface antigen (HBsAg) and surface antibodies (anti-HBs). A result of iAHBc could indicate a chronic occult bloodstream infection, necessitating further testing. This study assesses the prevalence and risk factors associated with anti-HBc and iAHBc within community high-risk screening in Greater Philadelphia. Participants (n = 177) were screened for HBsAg, anti-HBs, and anti-HBc during community screening events in 2022. Chi-square tables …

Microstructural Alterations Of Major Thalamic Nuclei In The Chronic Pediatric Spinal Cord Injured Population, K. Kang, K. Fleming, A. Sathe, J. Muller, J. Harrop, D. Middleton, J. Heller, A. Sharan, F. Mohamed, L. Krisa, M. Alizadeh

Department of Radiology Faculty Papers

BACKGROUND: The brain undergoes reorganization following spinal cord injury (SCI), but little is known about how the thalamus is affected in pediatric SCIs.

PURPOSE: To characterize microstructural alterations in the thalamus after SCI with diffusion tensor imaging (DTI) metrics.

METHODS: 18 pediatric participants with chronic SCI (8-20 years) were stratified using the American Spinal Injury Association Impairment Scale (AIS) into groups: A, B, and C/D. DTI of the brain used a 3 T Siemens Verio MRI using the parameters: 20 directions, number of averages = 3, b = 1000 s/mm

DATA ANALYSIS: DTI metrics were acquired by superimposing the AAL3 …

Diet And Nutrition In Inflammatory Bowel Disease: A Review Of The Literature, Scott Manski, Nicholas Noverati, Tatiana Policarpo, Emily Rubin, Raina Shivashankar

Division of Gastroenterology and Hepatology Faculty Papers

Diet is thought to contribute to the development of inflammatory bowel disease (IBD) and may act as a mediator of inflammation in patients with IBD. Patients commonly associate their diet with symptoms and inquire about dietary modifications to manage their IBD. Without clinical guidelines and well-established nutritional data, healthcare providers managing patients with IBD may find it difficult to provide recommendations. Strong evidence for enteral nutrition, particularly in the pediatric population, has been established in Crohn's disease (CD) as a therapeutic option. Enteral nutrition may also serve as an adjunct to an exclusion diet. Recent studies such as the randomized …

Sirtuin 6 Activation Rescues The Age-Related Decline In Dna Damage Repair In Primary Human Chondrocytes, Michaela E. Copp, Jacqueline Shine, Hannon L. Brown, Kirti R. Nimmala, Oliver B. Hansen, Susan Chubinskaya, John A. Collins, Richard F. Loeser, Brian O. Diekman

Department of Orthopaedic Surgery Faculty Papers

While advanced age is widely recognized as the greatest risk factor for osteoarthritis (OA), the biological mechanisms behind this connection remain unclear. Previous work has demonstrated that chondrocytes from older cadaveric donors have elevated levels of DNA damage as compared to chondrocytes from younger donors. The purpose of this study was to determine whether a decline in DNA repair efficiency is one explanation for the accumulation of DNA damage with age, and to quantify the improvement in repair with activation of Sirtuin 6 (SIRT6). After acute damage with irradiation, DNA repair was shown to be more efficient in chondrocytes from …

Identification Of Ct-Based Non-Invasive Radiomic Biomarkers For Overall Survival Prediction In Oral Cavity Squamous Cell Carcinoma, Xiao Ling, Gregory S. Alexander, Jason Molitoris, Jinhyuk Choi, Lisa Schumaker, Ranee Mehra, Daria A. Gaykalova, Lei Ren

Department of Radiation Oncology Faculty Papers

This study addresses the limited non-invasive tools for Oral Cavity Squamous Cell Carcinoma (OSCC) survival prediction by identifying Computed Tomography (CT)-based biomarkers to improve prognosis prediction. A retrospective analysis was conducted on data from 149 OSCC patients, including CT radiomics and clinical information. An ensemble approach involving correlation analysis, score screening, and the Sparse-L1 algorithm was used to select functional features, which were then used to build Cox Proportional Hazards models (CPH). Our CPH achieved a 0.70 concordance index in testing. The model identified two CT-based radiomics features, Gradient-Neighboring-Gray-Tone-Difference-Matrix-Strength (GNS) and normalized-Wavelet-LLL-Gray-Level-Dependence-Matrix-Large-Dependence-High-Gray-Level-Emphasis (HLE), as well as stage and alcohol usage, …

A Phenotypically Robust Model Of Spinal And Bulbar Muscular Atrophy In Drosophila, Kristin Richardson, Medha Sengupta, Alyson Sujkowski, Kozeta Libohova, Autumn C. Harris, Robert Wessells, Diane E. Merry, Sokol V. Todi

Department of Biochemistry and Molecular Biology Faculty Papers

Spinal and bulbar muscular atrophy (SBMA) is an X-linked disorder that affects males who inherit the androgen receptor (AR) gene with an abnormal CAG triplet repeat expansion. The resulting protein contains an elongated polyglutamine (polyQ) tract and causes motor neuron degeneration in an androgen-dependent manner. The precise molecular sequelae of SBMA are unclear. To assist with its investigation and the identification of therapeutic options, we report here a new model of SBMA in Drosophila melanogaster. We generated transgenic flies that express the full-length, human AR with a wild-type or pathogenic polyQ repeat. Each transgene is inserted into the same safe …

Novel Urine Cell-Free Dna Methylation Markers For Hepatocellular Carcinoma, Selena Lin, Wei Xia, Amy Kim, Dion Chen, Shelby Schleyer, Lin Choi, Zhili Wang, James Hamilton, Harry Luu, Hie-Won Hann, Ting-Tsung Chang, Chi-Tan Hu, Abashai Woodard, Terence Gade, Ying-Hsiu Su

Division of Gastroenterology and Hepatology Faculty Papers

An optimized hepatocellular carcinoma (HCC)-targeted methylation next generation sequencing assay was developed to discover HCC-associated methylation markers directly from urine for HCC screening. Urine cell-free DNA (ucfDNA) isolated from a discovery cohort of 31 non-HCC and 30 HCC was used for biomarker discovery, identifying 29 genes with differentially methylated regions (DMRs). Methylation-specific qPCR (MSqPCR) assays were developed to verify the selected DMRs corresponding to 8 genes (GRASP, CCND2, HOXA9, BMP4, VIM, EMX1, SFRP1, and ECE). Using archived ucfDNA, methylation of GRASP, HOXA9, BMP4, and ECE1, were found to be significantly different (p < 0.05) between HCC and non-HCC patients. The four markers together with previously reported GSTP1 and RASSF1A markers were assessed as a 6-marker panel in an independent training cohort of 87 non-HCC and 78 HCC using logistic regression modeling. AUROC of 0.908 (95% CI, 0.8656-0.9252) was identified for the 6-marker panel with AFP, which was significantly higher than AFP-alone (AUROC 0.841 (95% CI, 0.778-0.904), p = 0.0026). Applying backward selection method, a 4-marker panel was found to exhibit similar performance to the 6-marker panel with AFP having 80% sensitivity compared to 29.5% by AFP-alone at a specificity of 85%. This study supports the potential use of methylated transrenal ucfDNA for HCC screening.

Fluorescent Peptide For Detecting Factor Xiiia Activity And Fibrin In Whole Blood Clots Forming Under Flow, Yue Liu, Jennifer Crossen, Timothy J. Stalker, Scott L. Diamond

Cardeza Foundation for Hematologic Research

Background

During clotting, thrombin generates fibrin monomers and activates plasma-derived transglutaminase factor (F) XIIIa; collagen and thrombin-activated platelets offer thrombin-independent cellular FXIIIa (cFXIIIa) for clotting. Detecting fibrin on collagen and tissue factor surfaces in whole blood clotting typically uses complex reagents like fluorescent fibrinogen or antifibrin antibody.

Objectives

We want to test whether the peptide using the α2- antiplasmin crosslinking mechanism by FXIIIa is a useful tool in both monitoring FXIIIa activity, and visualize and monitor fibrin formation, deposition, and extent of crosslinking within fibrin structures in whole blood clots formed under flow.

Methods

We tested a fluorescent peptide derived …

Negative Pressure Wound Therapy For Complex Oral Wounds, Mykaihla Sternick, James Gates, Allen Champion, Andrew Yampolsky

Department of Oral and Maxillofacial Surgery Faculty Papers

Negative pressure wound therapy provides a nonsurgical treatment option for many types of complex wounds. This therapy utilizes the vacuum-assisted closure device, which decreases air pressure, removes fluid that accumulates within the wound, and aids to facilitate changes that promote healing. Despite the increased use of negative pressure wound therapy in the head and neck region, there is substantially less data available on the management of transoral vacuum-assisted wound closure. Herein, we present a case of a novel approach for the creation and use of a transoral wound vac for a patient with a refractory orocutaneous wound in the setting …

Simultaneous Detection Of Methylation And Genetic Variations Of Bcr-Abl1 Gene By Nanopore Cas9-Targeted Sequencing, Shuilian Xie, Ying Yang, Junjie Zhang, Menglin Zhu, Wang Li, Mengting Li, Yijian Chen, Hailiang Li, Weidan Lun, Weelic Chong, Shaogui Wan

Department of Medicine Faculty Papers

No abstract provided.

Robotic-Assisted Navigation For Stereotactic Neurosurgery: A Cadaveric Investigation Of Accuracy, Time, And Radiation, William Anderson, Francisco Ponce, Michael Kinsman, Sepehr Sani, Brian Hwang, Diana Ghinda, Michael Kogan, Jonathan M Mahoney, Dhara Amin, Margaret Van Horn, Joshua Mcguckin, Dominic Razo-Castaneda, Brandon Bucklen

Department of Neurosurgery Faculty Papers

BACKGROUND AND OBJECTIVES: Despite frequent use, stereotactic head frames require manual coordinate calculations and manual frame settings that are associated with human error. This study examines freestanding robot-assisted navigation (RAN) as a means to reduce the drawbacks of traditional cranial stereotaxy and improve targeting accuracy.

METHODS: Seven cadaveric human torsos with heads were tested with 8 anatomic coordinates selected for lead placement mirrored in each hemisphere. Right and left hemispheres of the brain were randomly assigned to either the traditional stereotactic arc-based (ARC) group or the RAN group. Both target accuracy and trajectory accuracy were measured. Procedural time and the …

Correction Of Spinal Sagittal Alignment After Posterior Lumbar Decompression: Does Severity Of Central Canal Stenosis Matter?, Delano Trenchfield, Yunsoo Lee, Mark J. Lambrechts, Nicholas D'Antonio, Jeremy Heard, John Paulik, Sydney Somers, Jeffrey Rihn, Mark Kurd, David Kaye, Jose Canseco, Alan Hilibrand, Alex Vaccaro, Christopher K Kepler, Gregory Schroeder

Rothman Institute Papers

STUDY DESIGN: This study adopted a retrospective study design.

PURPOSE: Our study aimed to investigate the impact of central canal stenosis severity on surgical outcomes and lumbar sagittal correction after lumbar decompression.

OVERVIEW OF LITERATURE: Studies have evaluated sagittal correction in patients with central canal stenosis after lumbar decompression and the association of stenosis severity with worse preoperative sagittal alignment. However, none have evaluated the impact of spinal stenosis severity on sagittal correction.

METHODS: Patients undergoing posterior lumbar decompression (PLD) of ≤4 levels were divided into severe and non-severe central canal stenosis groups based on the Lee magnetic resonance imaging …

Inhibition Of Neurogenic Inflammatory Pathways Associated With The Reduction In Discogenic Back Pain, Jose A. Canseco, Hannah A. Levy, Brian A. Karamian, Olivia Blaber, Michael Chang, Neil Patel, John G. Curran, Alan S. Hilibrand, Gregory D. Schroeder, Alex R. Vaccaro, Dessislava Z. Markova, David E. Surrey, Christopher K. Kepler

Rothman Institute Papers

STUDY DESIGN: Retrospective cohort study.

PURPOSE: This study aimed to determine whether the initiation of anti-calcitonin gene-related peptide (CGRP inhibitor) medication therapy for migraines was also associated with improvements in back/neck pain, mobility, and function in a patient population with comorbid degenerative spinal disease and migraine.

OVERVIEW OF LITERATURE: CGRP upregulates pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, brain-derived neurotrophic factor, and nerve growth factor in spinal spondylotic disease, which results in disc degeneration and sensitization of nociceptive neurons. Although CGRP inhibitors can quell neurogenic inflammation in migraines, their off-site efficacy as a therapeutic target for discogenic back/neck pain …

Feasibility Of Electronic Medication Monitoring Among Adolescents And Emerging Adults With Sickle Cell Disease, Aimee Hildenbrand, Katherine Kidwell, Meghan Mcgrady, Constance Mara, Charles Quinn, Lori Crosby

Department of Pediatrics Faculty Papers

Purpose: To examine the feasibility of using MEMS® bottles to assess adherence among adolescents and emerging adults with sickle cell disease.

Patients and Methods: Eighteen non-Hispanic Black participants with HbSS (M = 17.8 years; 61% male) were given a MEMS® bottle to store hydroxyurea (n = 14) or deferasirox (n = 4).

Results: One hundred percent initiated MEMS® use and 61% sustained use through the 18-week study; at follow-up, only 11% returned their bottle on time. Barriers to MEMS® use included medication changes and transition to adult care; facilitators included tip sheets and reminders.

Conclusion: While MEMS® is acceptable to …

Antiseizure Effects Of Peganum Harmala L. And Lavandula Angustifolia, Zahra Rahimian, Seyedhassan Sadrian, Mina Shahisavandi, Hadi Aligholi, Mohammad M. Zarshenas, Alireza Abyar, Zahra Zeraatpisheh, Ali A. Asadi-Pooya

Department of Neurology Faculty Papers

Peganum harmala L. and Lavandula angustifolia are two traditional herbs with probable antiseizure effects. This study evaluated the effects of these two herbal extracts on pentylenetetrazol- (PTZ-) induced seizures in mice. We prepared hydroalcoholic extracts using P. harmala seeds and the aerial parts of L. angustifolia and then randomly divided 190 mice into 19 groups. Normal saline (10 mg/kg), diazepam (2 mg/kg), P. harmala (2.5, 5, 10, 15, 30, 45, and 60 mg/kg), and L. angustifolia (200, 400, 600, and 800 mg/kg) were intraperitoneally (IP) administrated 30 min before an IP administration of PTZ (90 mg/kg). Animals were observed for …

Jun Upregulation Drives Aberrant Transposable Element Mobilization, Associated Innate Immune Response, And Impaired Neurogenesis In Alzheimer’S Disease, Chiara Scopa, Samantha Barnada, Maria Cicardi, Mo Singer, Davide Trotti, Marco Trizzino

Farber Institute for Neuroscience Faculty Papers

Adult neurogenic decline, inflammation, and neurodegeneration are phenotypic hallmarks of Alzheimer's disease (AD). Mobilization of transposable elements (TEs) in heterochromatic regions was recently reported in AD, but the underlying mechanisms are still underappreciated. Combining functional genomics with the differentiation of familial and sporadic AD patient derived-iPSCs into hippocampal progenitors, CA3 neurons, and cerebral organoids, we found that the upregulation of the AP-1 subunit, c-Jun, triggers decondensation of genomic regions containing TEs. This leads to the cytoplasmic accumulation of HERVK-derived RNA-DNA hybrids, the activation of the cGAS-STING cascade, and increased levels of cleaved caspase-3, suggesting the initiation of programmed cell death …

Changing The Playbook For Immigrant Health, Cheryl Bettigole, Patricia C. Henwood, Sage Myers, Maura Sammon

Department of Emergency Medicine Faculty Papers

Philadelphia’s response to welcoming Afghan evacuees during the COVID-19 pandemic suggests the need for a new approach to immigrant health care.

Phi-1, An Endogenous Inhibitor Protein For Protein Phosphatase-1 And A Pan-Cancer Marker, Regulates Raf-1 Proteostasis, Jason Kirkbride, Garbo Nilsson, Jee In Kim, Kosuke Takeya, Yoshinori Tanaka, Hiroshi Tokumitsu, Futoshi Suizu, Masumi Eto

Kimmel Cancer Center Faculty Papers

Raf-1, a multifunctional kinase, regulates various cellular processes, including cell proliferation, apoptosis, and migration, by phosphorylating MAPK/ERK kinase and interacting with specific kinases. Cellular Raf-1 activity is intricately regulated through pathways involving the binding of regulatory proteins, direct phosphorylation, and the ubiquitin-proteasome axis. In this study, we demonstrate that PHI-1, an endogenous inhibitor of protein phosphatase-1 (PP1), plays a pivotal role in modulating Raf-1 proteostasis within cells. Knocking down endogenous PHI-1 in HEK293 cells using siRNA resulted in increased cell proliferation and reduced apoptosis. This heightened cell proliferation was accompanied by a 15-fold increase in ERK1/2 phosphorylation. Importantly, the observed …