Digital Commons Network^™

Two-Pore Channel-2 And Inositol Trisphosphate Receptors Coordinate Ca2+ Signals Between Lysosomes And The Endoplasmic Reticulum, Yu Yuan, Vikas Arige, Ryo Saito, Qianru Mu, Gabriela C. Brailoiu, Gustavo J.S. Pereira, Stephen R. Bolsover, Marco Keller, Franz Bracher, Christian Grimm, Eugen Brailoiu, Jonathan S. Marchant, David I. Yule, Sandip Patel

College of Pharmacy Faculty Papers

Lysosomes and the endoplasmic reticulum (ER) are Ca2+ stores mobilized by the second messengers NAADP and IP3, respectively. Here, we establish Ca2+ signals between the two sources as fundamental building blocks that couple local release to global changes in Ca2+. Cell-wide Ca2+ signals evoked by activation of endogenous NAADP-sensitive channels on lysosomes comprise both local and global components and exhibit a major dependence on ER Ca2+ despite their lysosomal origin. Knockout of ER IP3 receptor channels delays these signals, whereas expression of lysosomal TPC2 channels accelerates them. High-resolution Ca2+ imaging reveals elementary events upon TPC2 opening and signals coupled to …

Chronic Hepatitis B: A Summarized Anecdote Of Complexities In Natural History, Treatment, And Complications, Nicholas Noverati, Jay W. Jun, Vivan Yan, Dina Halegoua-De Marzio, Hie-Won Hann

Division of Gastroenterology and Hepatology Faculty Papers

Chronic hepatitis B is still a disease process that affects millions around the world. Serologies used to diagnose and follow the progression (or resolution) of the disease can be confusing for clinicians. Further, throughout years of treatment, there may be nuances in presentation that complicate management even further. In this short communication, we highlight six themes in response to treatment and outcomes, including complications. We have the unique perspective of following many patients over extended periods of time at our institution, which has brought these themes to life in order that they can be shared with other clinicians who may …

A Prioritized Patient-Centered Research Agenda To Reduce Disparities In Telehealth Uptake: Results From A National Consensus Conference, Kristin L. Rising, Mackenzie Kemp, Amy E. Leader, Anna Marie Chang, Andrew J. Monick, Amanda Guth, Tracy Esteves Camacho, Gregory Laynor, Brooke Worster

Department of Emergency Medicine Faculty Papers

Introduction: We hosted a national consensus conference with a diverse group of stakeholders to develop a patient-centered research agenda focused on reducing disparities in telehealth use.

Methods: Attendees were purposively invited to participate in a 2-day virtual conference. The group developed a prioritized research agenda focused on reducing disparities in telehealth uptake, with discussion informed by findings from a scoping review. All work was conducted in partnership with a Steering Committee of national experts in telehealth and patient-centered care (n = 5) and a community-based Telehealth Advisory Board with experience with telehealth use and barriers (n = 8).

Results: Sixty …

Epilepsy Networks And Their Surgical Relevance, Kevin Hines, Chengyuan Wu

Department of Neurosurgery Faculty Papers

Surgical epilepsy is a rapidly evolved field. As the understanding and concepts of epilepsy shift towards a network disorder, surgical outcomes may shed light on numerous components of these systems. This review documents the evolution of the understanding of epilepsy networks and examines the data generated by resective, ablative, neuromodulation, and invasive monitoring surgeries in epilepsy patients. As these network tools are better integrated into epilepsy practice, they may eventually inform surgical decisions and improve clinical outcomes.

A Novel Multimodal Postoperative Pain Protocol For 1- To 2-Level Open Lumbar Fusions: A Retrospective Cohort Study, Michael Markowitz, Barrett I. Woods, Gregory D. Schroeder, Christopher K Kepler, David Kaye, Mark Kurd, Joshua Armstrong, Alex R. Vaccaro, Kris Radcliff

Rothman Institute Faculty Papers

BACKGROUND: There has been increased interest in exploring methods to reduce postoperative pain without opioid medications. In 2015, a multimodal analgesia protocol was used involving the perioperative use of celecoxib, gabapentin, intravenous acetaminophen, lidocaine, and liposomal bupivacaine. Overall, the goal was to reduce the utilization of scheduled opioids in favor of nonopioid pain management.

METHODS: The results of a consecutive series of 1- to 2-level open primary lumbar fusions were compared to a cohort of patients after the implementation the perioperative multimodal pain management protocol. Primary endpoints included patient-reported pain scores and secondary endpoints included length of stay.

RESULTS: There …

Effect Of Flecainide And Ibutilide Alone And In Combination To Terminate And Prevent Recurrence Of Atrial Fibrillation, Alexander Burashnikov, José M. Di Diego, Bence Patocskai, Debra S. Echt, Luiz Belardinelli, Charles Antzelevitch

Division of Cardiology Faculty Papers

BACKGROUND: There is a need for improved approaches to rhythm control therapy of atrial fibrillation (AF).

METHODS: The effectiveness of flecainide (1.5 µmol/L) and ibutilide (20 nmol/L), alone and in combination, to cardiovert and prevent AF recurrence was studied in canine-isolated coronary-perfused right atrioventricular preparations. We also examined the safety of the combination of flecainide (1.5 µmol/L) and ibutilide (50 nmol/L) using canine left ventricular wedge preparations.

RESULTS: Sustained AF (>1 hour) was inducible in 100%, 60%, 20%, and 0% of atria in the presence of acetylcholine alone, acetylcholine+ibutilide, acetylcholine+flecainide, and acetylcholine+ibutilide+flecainide, respectively. When used alone, flecainide and ibutilide …

Late-Onset Stiff-Person Syndrome: Challenges In Diagnosis And Management, Marinos Dalakas, Jessica Yi

Department of Neurology Faculty Papers

BACKGROUND: Stiff person syndrome (SPS) is a rare slowly progressive autoimmune neuronal hyperexcitability disease with very-high GAD-65 antibody titers that most commonly presents above the age of 20, with muscle stiffness, painful muscle spasms, slow gait, and falls leading to disability. In other autoimmune disorders, late-onset disease has different symptom-spectrum and outcomes, but there is no information regarding late-onset SPS (LOSPS).

OBJECTIVE: Highlight delayed diagnosis and poor tolerance or incomplete response to therapies of patients with LOSPS and outline how best to increase disease awareness early at onset.

DESIGN A RETROSPECTIVE CHART REVIEWMETHODS: We reviewed GAD-positive SPS patients with symptom …

Hormone Replacement Therapy Is Associated With Disease Activity Improvement Among Post-Menopausal Women With Inflammatory Bowel Disease, Morgan Freeman, Lauren Lally, Levi Teigen, Elliot Graziano, Raina Shivashankar, Eugenia Shmidt

Division of Gastroenterology and Hepatology Faculty Papers

(1) Background: There are limited data available to guide clinical decision-making regarding the effects of hormone replacement therapy (HRT) in post-menopausal women with inflammatory bowel disease (IBD). In this study, we sought to characterize a population of post-menopausal women with IBD and to determine the effects of HRT on their disease activity. (2) Methods: A multicenter, retrospective, case–control cohort study of post-menopausal women with IBD was conducted. The physician global assessment (PGA) score was used to quantify disease activity. To control for the effects of menopause, IBD patients who had not undergone HRT were used as controls. (3) Results: There …

Variables Affecting The Extraction Of Antioxidants In Cold And Hot Brew Coffee: A Review, Brian Yust, Frank Wilkinson, Niny Rao

College of Life Sciences Faculty Papers

Coffee beans are a readily available, abundant source of antioxidants used worldwide. With the increasing interest in and consumption of coffee beverages globally, research into the production, preparation, and chemical profile of coffee has also increased in recent years. A wide range of variables such as roasting temperature, coffee grind size, brewing temperature, and brewing duration can have a significant impact on the extractable antioxidant content of coffee products. While there is no single standard method for measuring all of the antioxidants found in coffee, multiple methods which introduce the coffee product to a target molecule or reagent can be …

Safety And Efficacy Of Ixoberogene Soroparvovec In Neovascular Age-Related Macular Degeneration In The United States (Optic): A Prospective, Two-Year, Multicentre Phase 1 Study, Arshad M. Khanani, David S. Boyer, Charles C. Wykoff, Carl D. Regillo, Brandon G. Busbee, Dante Pieramici, Carl J. Danzig, Brian C. Joondeph, James C. Major, Adam Turpcu, Szilárd Kiss

Wills Eye Hospital Papers

Background

Gene therapy, successfully used in rare, monogenetic disorders, may prove to be a durable management approach for common, polygenetic conditions, including neovascular age-related macular degeneration (nAMD). Repeated injections, oftentimes monthly, and possibly for decades, of vascular endothelial growth factor antagonists (anti-VEGF), is the standard for nAMD. We hypothesised that an in-office, intravitreal administration of ixoberogene soroparvovec (ixo-vec, formerly ADVM-022), a single-dose gene therapy encoding for the proven anti-VEGF protein, aflibercept, would transform retinal cells to continually produce aflibercept to minimise treatment burden in nAMD.

Methods

In this two-year, open-label, prospective, multicentre phase 1 study, patients with nAMD responding to …

The Function Of Ask1 In Sepsis And Stress-Induced Disorders, John Kostyak, Steven Mckenzie, Ulhas Naik

Cardeza Foundation for Hematologic Research

Apoptosis signal-regulating kinase 1 (ASK1) is a serine-threonine kinase that is ubiquitously expressed in nucleated cells and is responsible for the activation of multiple mitogen-activated protein kinases (MAPK) to regulate cell stress. Activation of ASK1 via cellular stress leads to activation of downstream signaling components, activation of transcription factors, and proinflammatory cytokine production. ASK1 is also expressed in anucleate platelets and is a key player in platelet activation as it is important for signaling. Interestingly, the mechanism of ASK1 activation is cell type-dependent. In this review we will explore how ASK1 regulates a variety of cellular processes from innate immune …

Autocrine Igf-Ii-Associated Cancers: From A Rare Paraneoplastic Event To A Hallmark In Malignancy, Pierluigi Scalia, Ignazio R. Marino, Salvatore Asero, Giuseppe Pandini, Adda Grimberg, Wafik S. El-Deiry, Stephen J. Williams

Department of Surgery Faculty Papers

The paraneoplastic syndrome referred in the literature as non-islet-cell tumor hypoglycemia (NICTH) and extra-pancreatic tumor hypoglycemia (EPTH) was first reported almost a century ago, and the role of cancer-secreted IGF-II in causing this blood glucose-lowering condition has been widely established. The landscape emerging in the last few decades, based on molecular and cellular findings, supports a broader role for IGF-II in cancer biology beyond its involvement in the paraneoplastic syndrome. In particular, a few key findings are constantly observed during tumorigenesis, (a) a relative and absolute increase in fetal insulin receptor isoform (IR^A) content, with (b) an increase …

Olanzapine Pharmacokinetics: A Clinical Review Of Current Insights And Remaining Questions, Priyanka Kolli, Grace Kelley, Marianela Rosales, Justin Faden, Ryan Serdenes

Department of Psychiatry and Human Behavior Faculty Papers

Olanzapine is one of the most widely used antipsychotics since its initial approval by the US Food and Drug Administration in 1996 and has undergone extensive pharmacokinetic study. Despite being utilized in clinical psychiatry for decades, there remain questions regarding the variety of available formulations, the utility of therapeutic drug monitoring, altered kinetic properties in special populations/medical illnesses, the use of high-dose olanzapine, and drug interactions, among many others. We performed a narrative literature review of olanzapine pharmacokinetics in June 2023 using the US National Library of Medicine's PubMed.gov resource (https://www.ncbi.nlm.nih.gov/pubmed) and Google Scholar. Herein, we review clinically relevant aspects …

Cabozantinib Plus Atezolizumab In Previously Untreated Advanced Hepatocellular Carcinoma And Previously Treated Gastric Cancer And Gastroesophageal Junction Adenocarcinoma: Results From Two Expansion Cohorts Of A Multicentre, Open-Label, Phase 1b Trial (Cosmic-021)., Daneng Li, Yohann Loriot, Adam Burgoyne, James Cleary, Armando Santoro, Daniel Lin, Santiago Ponce Aix, Ignacio Garrido-Laguna, Ramu Sudhagoni, Xiang Guo, Svetlana Andrianova, Scott Paulson

Kimmel Cancer Center Faculty Papers

BACKGROUND: Cabozantinib is approved for previously treated advanced hepatocellular carcinoma (aHCC) and has been investigated in gastric cancer (GC) and gastroesophageal junction adenocarcinoma (GEJ). Atezolizumab plus bevacizumab is approved for unresectable or metastatic HCC untreated with prior systemic therapy. We evaluated efficacy and safety of cabozantinib plus atezolizumab in aHCC previously untreated with systemic anticancer therapy or previously treated GC/GEJ.

METHODS: COSMIC-021 (ClinicalTrials.gov, NCT03170960) is an open-label, phase 1b study in solid tumours with a dose-escalation stage followed by tumour-specific expansion cohorts, including aHCC (cohort 14) and GC/GEJ (cohort 15). Eligible patients were aged ≥18 years with measurable locally advanced, …

Harm Reduction In Undergraduate And Graduate Medical Education: A Systematic Scoping Review, Kelsey R. Smith, Nina K. Shah, Abby L. Adamczyk, Lara C. Weinstein, Erin L. Kelly

Department of Family & Community Medicine Faculty Papers

BACKGROUND: Substance use increasingly contributes to early morbidity and mortality, which necessitates greater preparation of the healthcare workforce to mitigate its harm. The purpose of this systematic scoping review is to: 1) review published curricula on harm reduction for substance use implemented by undergraduate (UME) and graduate medical education (GME) in the United States and Canada, 2) develop a framework to describe a comprehensive approach to harm reduction medical education, and 3) propose additional content topics for future consideration.

METHODS: PubMed, Scopus, ERIC: Education Resources Information Center (Ovid), and MedEdPORTAL were searched. Studies included any English language curricula about harm …

Immunosequencing Applications In Cutaneous T-Cell Lymphoma, Jenna Mandel, Laura Gleason, Daniel Joffe, Safiyyah Bhatti, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

Immunosequencing has emerged as a newer clinical test for assessment of T-cell clonality in the blood and skin of cutaneous T-cell lymphoma (CTCL) patients. Utilization of immunosequencing, also known as high-throughput sequencing of the T-cell receptor (HTS-TCR), enables identification and quantification of the precise genetic signature of dominant T-cell clones. Although immunosequencing is more sensitive than commonly used methods such as polymerase chain reaction (PCR) paired with capillary electrophoresis or flow cytometry, it remains underutilized for CTCL management. Nonetheless, incorporation of HTS-TCR in clinical practice offers distinct advantages compared to other molecular analyses that may improve diagnostic evaluation, prognostication, and …

27-Hydroxycholesterol And Dna Damage Repair: Implication In Prostate Cancer, Gloria Cecilia Galvan, Nadine Friedrich, Sanjay Das, James Daniels, Sara Pollan, Shweta Dambal, Ryusuke Suzuki, Sergio Sanders, Sungyong You, Hisashi Tanaka, Yeon-Joo Lee, Wei Yuan, Johann De Bono, Irina Vasilevskaya, Karen Knudsen, Michael Freeman, Stephen Freedland

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

INTRODUCTION: We previously reported that cholesterol homeostasis in prostate cancer (PC) is regulated by 27-hydroxycholesterol (27HC) and that CYP27A1, the enzyme that converts cholesterol to 27HC, is frequently lost in PCs. We observed that restoring the CYP27A1/27HC axis inhibited PC growth. In this study, we investigated the mechanism of 27HC-mediated anti-PC effects.

METHODS: We employed in vitro models and human transcriptomics data to investigate 27HC mechanism of action in PC. LNCaP (AR+) and DU145 (AR-) cells were treated with 27HC or vehicle. Transcriptome profiling was performed using the Affymetrix GeneChip™ microarray system. Differential expression was determined, and gene set enrichment …

The Concise Guide To Pharmacology 2023/24: Catalytic Receptors, Stephen P.H. Alexander, Doriano Fabbro, Eamonn Kelly, Alistair A. Mathie, John A. Peters, Emma L. Veale, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, Jamie A. Davies, Annie Beuve, Peter Brouckaert, Clare Bryant, John C. Burnett, Richard W. Farndale, Andreas Friebe, John Garthwaite, Adrian J. Hobbs, Gavin E. Jarvis, Doris Koesling, Michaela Kuhn, David Macewan, Tom P. Monie, Lincoln R. Potter, Michael Russwurm, Harald H.H.W. Schmidt, Johannes-Peter Stasch, Scott A. Waldman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and nearly 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It …

Rapidiron Trial Follow-Up Study - The Rapidiron-Kids Study: Protocol Of A Prospective Observational Follow-Up Study, Richard Derman, Roopa Bellad, Mrutyunjaya Bellad, Jesse Bradford-Rogers, Michael Georgieff, Zubair Aghai, Simal Thind, Michael Auerbach, Rupsa Boelig, Benjamin Leiby, Vanessa Short, S. Yogeshkumar, Umesh Charantimath, Manjunath Somannavar, Ashalata Mallapur, Ramesh Pol, Umesh Ramadurg, Radha Sangavi, Basavaraj Peerapur, Nasima Banu, Praveen Patil, Amaresh Patil, Subarna Roy, Phaniraj Vastrad, Dennis Wallace, Hemang Shah, Shivaprasad Goudar

Global Health Articles

BACKGROUND: Anemia is a worldwide problem with iron deficiency being the most common cause. When anemia occurs in pregnancy, it increases the risk of adverse maternal, fetal, and postnatal outcomes. It induces preterm births and low birth weight (LBW) deliveries, long-term neurodevelopmental sequelae, and an increased risk of earlier onset of postnatal iron deficiency. Anemia rates are among the highest in South Asia, and India's National Family Health Survey (NFHS-5) for 2019-2021 indicated that over half of pregnant women, and more than 65% of children, in the country are classified as anemic (Sciences IIfP, National Family Health Survey-5, 2019-21, India …

Prt543, A Protein Arginine Methyltransferase 5 Inhibitor, In Patients With Advanced Adenoid Cystic Carcinoma: An Open-Label, Phase I Dose-Expansion Study, Renata Ferrarotto, Paul Swiecicki, Dan Zandberg, Robert Baiocchi, Robert Wesolowski, Cristina Rodriguez, Meredith Mckean, Hyunseok Kang, Varun Monga, Rajneesh Nath, Neil Palmisiano, Naveen Babbar, William Sun, Glenn Hanna

Department of Medical Oncology Faculty Papers

OBJECTIVES: Currently, no systemic treatments are approved for patients with recurrent and/or metastatic (R/M) adenoid cystic carcinoma (ACC). PRT543, a protein arginine methyltransferase 5 inhibitor that downregulates NOTCH1 and MYB signalling in tumours, is a potential candidate for R/M ACC treatment. We report the safety, tolerability and preliminary efficacy of PRT543 in a dose-expansion cohort of patients with R/M ACC.

MATERIALS AND METHODS: This phase I multicentre, open-label, sequential-cohort, dose-escalation and dose-expansion study (NCT03886831) enrolled patients with advanced solid tumours and select haematologic malignancies. Dose-escalation study design and results were reported previously. In the dose expansion, patients with R/M ACC …

Stereotactic Mr-Guided On-Table Adaptive Radiation Therapy (Smart) For Borderline Resectable And Locally Advanced Pancreatic Cancer: A Multi-Center, Open-Label Phase 2 Study, Michael Chuong, Percy Lee, Daniel Low, Joshua Kim, Kathryn Mittauer, Michael Bassetti, Carri Glide-Hurst, Ann Raldow, Yingli Yang, Lorraine Portelance, Kyle Padgett, Bassem Zaki, Rongxiao Zhang, Hyun Kim, Lauren Henke, Alex Price, Joseph Mancias, Christopher Williams, John Ng, Ryan Pennell, M Raphael Pfeffer, Daphne Levin, Adam Mueller, Karen Mooney, Patrick Kelly, Amish Shah, Luca Boldrini, Lorenzo Placidi, Martin Fuss, Parag Jitendra Parikh

Department of Radiation Oncology Faculty Papers

BACKGROUND AND PURPOSE: Radiation dose escalation may improve local control (LC) and overall survival (OS) in select pancreatic ductal adenocarcinoma (PDAC) patients. We prospectively evaluated the safety and efficacy of ablative stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for borderline resectable (BRPC) and locally advanced pancreas cancer (LAPC). The primary endpoint of acute grade ≥ 3 gastrointestinal (GI) toxicity definitely related to SMART was previously published with median follow-up (FU) 8.8 months from SMART. We now present more mature outcomes including OS and late toxicity.

MATERIALS AND METHODS: This prospective, multi-center, single-arm open-label phase 2 trial (NCT03621644) enrolled 136 …

The Pharmacological Deprescription In Elderly Patients, Chelsey Ali, Daniel Huang, Charlene Tugwete, Stefano Del Canale, Vittorio Maio

College of Population Health Faculty Papers

No abstract provided.

Extended-Synaptotagmin-1 And -2 Control T Cell Signaling And Function, Nathalia Benavides, Claudio G. Giraudo

Department of Microbiology and Immunology Faculty Papers

Upon T-cell activation, the levels of the secondary messenger diacylglycerol (DAG) at the plasma membrane need to be controlled to ensure appropriate T-cell receptor signaling and T-cell functions. Extended-Synaptotagmins (E-Syts) are a family of inter-organelle lipid transport proteins that bridge the endoplasmic reticulum and the plasma membrane. In this study, we identify a novel regulatory mechanism of DAG-mediated signaling for T-cell effector functions based on E-Syt proteins. We demonstrate that E-Syts downmodulate T-cell receptor signaling, T-cell-mediated cytotoxicity, degranulation, and cytokine production by reducing plasma membrane levels of DAG. Mechanistically, E-Syt2 predominantly modulates DAG levels at the plasma membrane in resting-state …

Needle Biopsy Accelerates Pro-Metastatic Changes And Systemic Dissemination In Breast Cancer: Implications For Mortality By Surgery Delay, Hiroyasu Kameyama, Priya Dondapati, Reese Simmons, Macall Leslie, John Langenheim, Yunguang Sun, Misung Yi, Aubrey Rottschaefer, Rashmi Pathak, Shreya Nuguri, Kar-Ming Fung, Shirng-Wern Tsaih, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

ncreased breast cancer (BC) mortality risk posed by delayed surgical resection of tumor after diagnosis is a growing concern, yet the underlying mechanisms remain unknown. Our cohort analyses of early-stage BC patients reveal the emergence of a significantly rising mortality risk when the biopsy-to-surgery interval was extended beyond 53 days. Additionally, histology of post-biopsy tumors shows prolonged retention of a metastasis-permissive wound stroma dominated by M2-like macrophages capable of promoting cancer cell epithelial-to-mesenchymal transition and angiogenesis. We show that needle biopsy promotes systemic dissemination of cancer cells through a mechanism of sustained activation of the COX-2/PGE₂/EP2 feedforward loop, …

Treatment Response Of Gingival Squamous-Cell Carcinoma To Palliative Intent Immunotherapy, Natalia Trehan, Angelina Debbas, Mykaihla Sternick, Jennifer Johnson, James Gates

Department of Medical Oncology Faculty Papers

The use of PD-1 immune checkpoint inhibitor medications has become a common practice in the treatment of recurrent and metastatic head and neck squamous-cell carcinomas. Success in this setting has led to the investigation of their efficacy in locally advanced cases as a part of first-line therapy. In this report, we detail the treatment response to palliative intent immunotherapy of three geriatric patients with mandibular gingival squamous-cell carcinoma who decided against surgical intervention. Patient #1 was treated with pembrolizumab, a PD-1 inhibitor, and displayed complete clinical and radiologic response of the gingival mass after three months of treatment, which is …

Interprofessional Perspectives On School-Wide Mental Health Interventions For Enhancing Resilience In Adolescents, Danielle Costanzo, Ms, Otr/L

Post-Professional Occupational Therapy Doctorate Culminating Presentations

Introduction: There is a significant crisis in adolescent mental health (American Academy of Pediatrics, 2021; Radhakrishnan et al., 2022) that have been compounded by traumatic experiences experienced during the COVID-19 pandemic (Substance Abuse and Mental Health Services Administration, 2022) and widespread fear of violence in schools (Silver et al., 2021). The crisis and resulting vulnerability has led to a dire need to focus on overcoming mental health challenges and moving forward in the face of adversity, which calls for a focus on resilience to promote overall life outcomes (Fenwick-Smith et al., 2019; Ijadi-Maghsoodi et al., 2022; Steiner et al., 2019). …

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 …

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 …

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 …