Digital Commons Network^™

Fibroblast-Derived Pi16 Sustains Inflammatory Pain Via Regulation Of Cd206+ Myeloid Cells, Rachelle Garrity, Neha Arora, Md Areeful Haque, Drew Weis, Ronnie T Trinh, Susmita Kumari, Eroboghene E Ubogu, Rajasekaran Mahalingam, Diana Tavares-Ferreira, Theodore J Price, Annemieke Kavelaars, Cobi J Heijnen, Andrew J Shepherd

Faculty, Staff and Student Publications

Originally identified in fibroblasts, Protease Inhibitor (PI)16 was recently shown to be crucial for the development of neuropathic pain via effects on blood-nerve barrier permeability and leukocyte infiltration, though its impact on inflammatory pain has not been established. Using the complete Freund’s Adjuvant inflammatory pain model, we show that Pi16-/- mice are protected against sustained inflammatory pain. Accordingly, intrathecal delivery of a PI16 neutralizing antibody in wild-type mice prevented sustained CFA pain. In contrast to neuropathic pain models, we did not observe any changes in blood-nerve barrier permeability due to PI16 deletion. Instead, Pi16-/- mice display reduced macrophage density …

Primary Balloon Angioplasty Of Venous Sinus Stenosis In Idiopathic Intracranial Hypertension, Rosa Tang, Allison C Engstrom, Sunil Sheth, Claudia Pedroza, Arthur L Day, Peng Roc Chen

Faculty, Staff and Student Publications

Background: Venous sinus stenosis (VSS) stenting has emerged as an effective treatment for patients with Idiopathic Intracranial Hypertension (IIH). However, stenting carries risk of in-stent stenosis/thrombosis and cumulative bleeding risk from long-term dual antiplatelet (DAPT) use. Thus, we investigated the potential safety and efficacy of primary balloon angioplasty as an alternative to stenting in IIH.

Methods: A prospectively maintained single-center registry of IIH patients undergoing endovascular procedures was queried. Inclusion criteria included patients with confirmed IIH and angiographically demonstrable VSS who underwent interventions from 2012- 2021. Patients were dichotomized into primary balloon angioplasty (Group A) and primary stenting (Group S), …

Eosinophils Promote Effector Functions Of Lung Group 2 Innate Lymphoid Cells In Allergic Airway Inflammation In Mice, Alfred D Doyle, Hirohito Kita, Elizabeth A Jacobsen

Faculty, Staff and Student Publications

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) are critical mediators of type 2 respiratory inflammation, releasing IL-5 and IL-13 and promoting the pulmonary eosinophilia associated with allergen provocation. Although ILC2s have been shown to promote eosinophil activities, the role of eosinophils in group 2 innate lymphoid cell (ILC2) responses is less well defined.

OBJECTIVE: We sought to investigate the role of eosinophils in activation of ILC2s in models of allergic asthma and in vitro.

METHODS: Inducible eosinophil-deficient mice were exposed to allergic respiratory inflammation models of asthma, such as ovalbumin or house dust mite challenge, or to innate models of …

Dissemination Of Class A Cephalosporinases And Class D Carbapenemases In Escherichia Coli Isolates From A Tertiary Hospital In Sudan

Faculty, Staff and Student Publications

Introduction

The high prevalence of urinary tract infections (UTIs) and rising resistance to beta-lactam antibiotics, which is a global therapeutic concern, are caused by Escherichia coli (E. coli) extended-spectrum beta-lactamases (ESBLs) producers. It is unclear how E. coli that produces ESBLs spreads throughout Gezira state, Sudan. The study aimed to evaluate the dissemination of class A and class D resistance genes among E. coli and to recognize the antibacterial activity of the locally used cephalosporins and carbapenems.

Methods

One hundred and fifteen isolates of uropathogenic E. coli were collected from patients who attended a tertiary hospital. The isolates …

Cooperative Activation Of Pdk1 And Akt By Mapk4 Enhances Cancer Growth And Resistance To Therapy, Tao Shen, Xiangsheng Huang, Ping Yi, Bingning Dong, Feng Yang

Faculty, Staff and Students Publications

Phosphoinositide-dependent kinase-1 (PDK1) is a master kinase of the protein A, G, and C (AGC) family kinases that play important roles in regulating cancer cell proliferation, survival, and metabolism. Besides phosphorylating/activating AKT at the cell membrane in a PI3K-dependent manner, PDK1 also exhibits constitutive activity on many other AGC kinases for tumor-promoting activity. In the latter case, PDK1 protein levels dominate its activity. We previously reported that MAPK4, an atypical MAPK, can PI3K-independently promote AKT activation and tumor growth. Here, using triple-negative breast cancer (TNBC) cell models, we demonstrate that MAPK4 can also enhance PDK1 protein synthesis, thus phosphorylate/activate PDK1 …

Proteomics Of Adjacent-To-Tumor Samples Uncovers Clinically Relevant Biological Events In Hepatocellular Carcinoma, Shisheng Wang, Yuejia Liu, Liangqing Dong, Qian Meng, Jing Gao, Yuqiu Wang, Nixue Song, Yuying Suo, Li Ding, Pei Wang, Bing Zhang, Daming Gao, Jia Fan, Qiang Gao, Hu Zhou

Faculty, Staff and Students Publications

Normal adjacent tissues (NATs) of hepatocellular carcinoma (HCC) differ from healthy liver tissues and their heterogeneity may contain biological information associated with disease occurrence and clinical outcome that has yet to be fully evaluated at the proteomic level. This study provides a detailed description of the heterogeneity of NATs and the differences between NATs and healthy livers and revealed that molecular features of tumor subgroups in HCC were partially reflected in their respective NATs. Proteomic data classified HCC NATs into two subtypes (Subtypes 1 and 2), and Subtype 2 was associated with poor prognosis and high-risk recurrence. The pathway and …

Exploring Gastrointestinal Health In Mecp2 Duplication Syndrome, Bernhard Suter, Kathleen J Motil

Faculty, Staff and Students Publications

BACKGROUND: MECP2 duplication syndrome (MDS) is a rare neurogenetic syndrome caused by duplications of MECP2 at the Xq28 region. Although constipation and gastrointestinal reflux are reported in MDS, a comprehensive characterization of gastrointestinal health has not been fully explored.

METHODS: We conducted a parent survey to explore the characteristics of gastrointestinal health in individuals with MDS using a secure online registry and compared differences in gastrointestinal symptoms between individuals with MDS and those with Rett syndrome (RTT).

KEY RESULTS: One hundred six surveys were analyzed. Symptoms commonly associated with constipation occurred in 72% to 89% of MDS individuals. Eleven percent …

Real-Time, Deep-Learning Aided Lensless Microscope, Jacob T Robinson

Faculty, Staff and Students Publications

Traditional miniaturized fluorescence microscopes are critical tools for modern biology. Invariably, they struggle to simultaneously image with a high spatial resolution and a large field of view (FOV). Lensless microscopes offer a solution to this limitation. However, real-time visualization of samples is not possible with lensless imaging, as image reconstruction can take minutes to complete. This poses a challenge for usability, as real-time visualization is a crucial feature that assists users in identifying and locating the imaging target. The issue is particularly pronounced in lensless microscopes that operate at close imaging distances. Imaging at close distances requires shift-varying deconvolution to …

Mönckeberg's Medial Calcific Sclerosis Makes Traditional Arterial Doppler's Unreliable In High-Risk Patients With Diabetes, Mehmet A. Suludere, Sahab K. Danesh, Amanda L. Killeen, Peter A. Crisologo, Matthew Malone, Michael C. Siah, Lawrence A. Lavery

School of Podiatric Medicine Publications

Objective

To assess Mönckeberg's medial calcific sclerosis (MMCS) severity in patients with a diabetic foot infection.

Methods

This was an analysis of 2 randomized clinical trials in which we evaluated the treatment of 233 patients admitted to the hospital for moderate and severe foot infections. Arterial calcification was defined as visible radiopaque arteries on foot and ankle radiographs, recorded as the most distal visible artery involved (toes, metatarsals, and ankle/hindfoot).

Results

Most subjects (57.1%, n = 133) had MMCS, with extension to toes in 79 (59.4%), to metatarsals in 32 (24.1%), and to ankle/hindfoot in 22 patients (16.5%). In 7 …

The Role Of Fas Receptor Methylation In Osteosarcoma Metastasis, M John Hicks, Manjula Nakka, Jianhe Shen, Patrick Kwok Shing Ng, Aaron M Taylor, Alexander Yu, Jason E Farrar, Donald A Barkauskas, Richard Gorlick, Jaime M Guidry Auvil, Daniela Gerhard, Paul Meltzer, Rudy Guerra, Tsz-Kwong Man, Ching C Lau, On Behalf Of The Target Osteosarcoma Consortium

Faculty, Staff and Students Publications

Osteosarcoma is the most frequent primary malignant bone tumor with an annual incidence of about 400 cases in the United States. Osteosarcoma primarily metastasizes to the lungs, where FAS ligand (FASL) is constitutively expressed. The interaction of FASL and its cell surface receptor, FAS, triggers apoptosis in normal cells; however, this function is altered in cancer cells. DNA methylation has previously been explored as a mechanism for altering FAS expression, but no variability was identified in the CpG island (CGI) overlapping the promoter. Analysis of an expanded region, including CGI shores and shelves, revealed high variability in the methylation of …

Automated Capture And Analysis Of Circulating Tumor Cells In Pediatric, Adolescent And Young Adult Patients With Central Nervous System Tumors, Wafik Zaky, Dristhi Ragoonanan, Izhar Batth, Long Dao, Jian Wang, Najat C Daw, Soumen Khatua, Shulin Li

Faculty, Staff and Student Publications

Tumors of the central nervous system (CNS) are the most common and lethal childhood malignancy. Detection of residual disease and longitudinal monitoring of treatment response in patients are challenging and rely on serial imaging. This current standard of care fails to detect microscopic disease or provide molecular characteristics of residual tumors. As such, there is dire need for minimally invasive liquid biopsy techniques. We have previously shown the high specificity of using cell surface vimentin (CSV) to identify circulating tumor cells (CTCs) from patients bearing various types of cancers. Here, we describe the first report of CTCs captured from peripheral …

Nanoparticle-Mediated Therapy With Mir-198 Sensitizes Pancreatic Cancer To Gemcitabine Treatment Through Downregulation Of Vcp-Mediated Autophagy, Zhengdong Liang, Osvaldo Vega-Martínez, Sue E Crawford, Mary K Estes, William E Fisher, Changyi Chen, Qizhi Yao

Faculty, Staff and Students Publications

Pancreatic ductal adenocarcinoma (PDAC) remains an extremely aggressive disease characterized by rapidly acquired multi-drug resistance, including to first-line chemotherapeutic agent gemcitabine. Autophagy is a process that is often exploited by cancer and is one of several intrinsic factors associated with resistance to gemcitabine. We have previously found that miR-198 acts as a tumor suppressor in PDAC through the targeting of factors including Valosin-containing protein (VCP). VCP has been reported to play an important role in autophagic flux. In this study, we investigated whether the repression of VCP through miR-198 administration disrupts the autophagy process and sensitizes PDAC cells to gemcitabine …

Tp53 Induced Glycolysis And Apoptosis Regulator And Monocarboxylate Transporter 4 Drive Metabolic Reprogramming With C-Myc And Nfkb Activation In Breast Cancer, Megan E. Roche, Ying-Hui Ko, Marina Domingo-Vidal, Zhao Lin, Diana Whitaker-Menezes, Ruth C. Birbe, Madalina Tuluc, Balázs Győrffy, Jaime Caro, Nancy J. Philp, Ramon Bartrons, Ubaldo Martinez-Outshoorn

Department of Medical Oncology Faculty Papers

Breast cancer is composed of metabolically coupled cellular compartments with upregulation of TP53 Induced Glycolysis and Apoptosis Regulator (TIGAR) in carcinoma cells and loss of caveolin 1 (CAV1) with upregulation of monocarboxylate transporter 4 (MCT4) in fibroblasts. The mechanisms that drive metabolic coupling are poorly characterized. The effects of TIGAR on fibroblast CAV1 and MCT4 expression and breast cancer aggressiveness was studied using coculture and conditioned media systems and in-vivo. Also, the role of cytokines in promoting tumor metabolic coupling via MCT4 on cancer aggressiveness was studied. TIGAR downregulation in breast carcinoma cells reduces tumor growth. TIGAR overexpression in carcinoma …

Cardiovascular Disease In Saudi Arabia: Facts And The Way Forward, Adel Abdulkader Tash, Rasha Fahad Al-Bawardy

Journal of the Saudi Heart Association

While some risk factors for cardiovascular diseases (CVDs) are non-modifiable, other determinants like obesity, hypertension, type-2 diabetes and dyslipidemia can be mitigated by a wide plethora of measures to control CVD morbidity/mortality. Those determinants have been on the rise in Saudi Arabia, exacerbated by sedentary lifestyle. The Saudi Vision 2030 focuses include the reduction of CVD clinical and economic burden to scale-up vitality and longevity; in a new era of comprehensive healthcare. From a health economics standpoint, CVDs entail a burden on healthcare systems directly through expenditure and indirectly through years living with the disease, low productivity, premature morbidity and …

Editorial: Intervertebral Disc Degeneration And Osteoarthritis: Mechanisms Of Disease And Functional Repair., Graciosa Q Teixeira, Jana Riegger, Raquel M Gonçalves, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

No abstract provided.

Surface-Doped Zinc Gallate Colloidal Nanoparticles Exhibit Ph-Dependent Radioluminescence With Enhancement In Acidic Media, Amar S Kumbhar, Jianguo Wen, Zhiping Luo

Faculty, Staff and Student Publications

As abnormal acidic pH symbolizes dysfunctions of cells, it is highly desirable to develop pH-sensitive luminescent materials for diagnosing disease and imaging-guided therapy using high-energy radiation. Herein, we explored near-infrared-emitting Cr-doped zinc gallate ZnGa2O4 nanoparticles (NPs) in colloidal solutions with different pH levels under X-ray excitation. Ultrasmall NPs were synthesized via a facile hydrothermal method by controlling the addition of ammonium hydroxide precursor and reaction time, and structural characterization revealed Cr dopants on the surface of NPs. The synthesized NPs exhibited different photoluminescence and radioluminescence mechanisms, confirming the surface distribution of activators. It was observed that the colloidal NPs emit …

A Case Presentation Of Pericarditis Associated With Haemophilus Influenzae Bacteremia, Risa Goldberg, Md, Harrison Bell, Md

The Medicine Forum

Acute pericarditis, or inflammation of the pericardial sac, is a clinical condition which can often be attributed to a variety of underlying etiologies, including infection, autoimmune disease, trauma, and malignancy. While viral infections are commonly implicated in the etiology of pericarditis, bacteria known to be associated with pericarditis include staphylococcus species, streptococcal species, tuberculosis, and in children, Haemophilus influenzae.¹ Here we present a rare case of pericarditis in an adult male patient which occurred in association with Haemophilus influenzae bacteremia.

The Medicine Forum: Volume 24

The Medicine Forum

The Journal of Thomas Jefferson University Hospital - Department of Internal Medicine, Volume 24, 2022-2023

TABLE OF CONTENTS

• Case Reports
• Ultrasound Education

Editorial: Targeting Dna Damage Response To Enhance Antitumor Innate Immunity In Radiotherapy, Victoria Valvo, Emanuele Vitale, Marco Tigano, Rachel Evans, Meredith A. Morgan, Qiang Zhang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.

The Mastery Lifestyle Intervention To Reduce Biopsychosocial Risks For Pregnant Latinas And African Americans And Their Infants: Protocol For A Randomized Controlled Trial, Asim C Akbulut, Armand M Jaminon, Ehsan Natour, Roberto Lorusso, Joachim E Wildberger, Barend Mees, Geert Willem Schurink, Michael J Jacobs, Jack Cleutjens, Ingrid Krapels, Alexander Gombert, Jos G Maessen, Ryan Accord, Tammo Delhaas, Simon Schalla, Leon J Schurgers, Elham Bidar

Faculty, Staff and Student Publications

Current management guidelines for ascending thoracic aortic aneurysms (aTAA) recommend intervention once ascending or sinus diameter reaches 5-5.5 cm or shows a growth rate of >0.5 cm/year estimated from echo/CT/MRI. However, many aTAA dissections (aTAAD) occur in vessels with diameters below the surgical intervention threshold ofMoreover, during aTAA repair surgeons observe and experience considerable variations in tissue strength, thickness, and stiffness that appear not fully explained by patient risk factors. To improve the understanding of aTAA pathophysiology, we established a multi-disciplinary research infrastructure: The Maastricht acquisition platform for studying mechanisms of tissue-cell crosstalk (MAPEX). The explicit scientific focus of the …

Natriuretic Peptide Biomarkers In The Imminent Development Of Preeclampsia., Stefanie Marek-Iannucci, Estefania Oliveros, Yevgeniy Brailovsky, Preethi Pirlamarla, Amanda Roman, Indranee Rajapreyar

Division of Cardiology Faculty Papers

Preeclampsia is the most common cause of morbidity and mortality in pregnancy, the incidence being significantly higher in low-income countries with reduced access to health care. Women with preeclampsia are at a higher risk of developing cardiovascular disease with a poorer long-term outcome. Early recognition and treatment are key to improving short- and long-term outcomes. Approximately 3%-5% of pregnant women will develop preeclampsia, with potentially fatal outcomes. Despite ongoing research, the exact pathophysiologic mechanism behind its development remains unclear. In this brief report, we describe the potential role of natriuretic peptides as biomarkers in the imminent development of preeclampsia. In …

Comparison Of Dna Vaccines With As03 As An Adjuvant And An Mrna Vaccine Against Sars-Cov-2, Navid Sobhani, George Udeani, Yong Li

Faculty, Staff and Students Publications

Emerging variants of SARS-CoV-2 call for frequent changes in vaccine antigens. Nucleic acid-based vaccination strategies are superior as the coding sequences can be easily altered with little impact on downstream production. mRNA vaccines, including variant-specific boosters, are approved for SARS-CoV-2. Here, we tested the efficacy of DNA vaccines against the SARS-CoV-2 Spike aided by the AddaS03 adjuvant using electroporation and compared their immunogenicity with an approved mRNA vaccine (mRNA-1273). DNA vaccination elicited robust humoral and cellular immune responses in C57BL/6 mice with Spike-specific antibody neutralization and T cells produced from 20 μg DNA vaccines similar to that from 0.5 μg …

Targeting Polyploid Giant Cancer Cells Potentiates A Therapeutic Response And Overcomes Resistance To Parp Inhibitors In Ovarian Cancer, Xudong Zhang, Jun Yao, Xiaoran Li, Na Niu, Yan Liu, Guang Peng, Anil K Sood, Jinsong Liu

Faculty, Staff and Student Publications

To understand the mechanism of acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) olaparib, we induced the formation of polyploid giant cancer cells (PGCCs) in ovarian and breast cancer cell lines, high-grade serous cancer (HGSC)-derived organoids, and patient-derived xenografts (PDXs). Time-lapse tracking of ovarian cancer cells revealed that PGCCs primarily developed from endoreplication after exposure to sublethal concentrations of olaparib. PGCCs exhibited features of senescent cells but, after olaparib withdrawal, can escape senescence via restitutional multipolar endomitosis and other noncanonical modes of cell division to generate mitotically competent resistant daughter cells. The contraceptive drug mifepristone blocked PGCC formation and daughter cell …

Gold Nanoparticles For Monitoring Of Mesenchymal Stem-Cell-Loaded Bioresorbable Polymeric Wraps For Arteriovenous Fistula Maturation, Allan John R Barcena, Joy Vanessa D Perez, Jossana A Damasco, Marvin R Bernardino, Erin Marie D San Valentin, Benjamin Martin, Gino Martin Canlas, Huckie C Del Mundo, Francisco M Heralde, Rony Avritscher, Natalie Fowlkes, Richard R Bouchard, Jizhong Cheng, Steven Y Huang, Marites P Melancon

Faculty, Staff and Student Publications

Mesenchymal stem cell (MSC)-seeded polymeric perivascular wraps have been shown to enhance arteriovenous fistula (AVF) maturation. However, the wraps' radiolucency makes their placement and integrity difficult to monitor. Through electrospinning, we infused gold nanoparticles (AuNPs) into polycaprolactone (PCL) wraps to improve their radiopacity and tested whether infusion affects the previously reported beneficial effects of the wraps on the AVF's outflow vein. Sprague Dawley rat MSCs were seeded on the surface of the wraps. We then compared the effects of five AVF treatments-no perivascular wrap (i.e., control), PCL wrap, PCL + MSC wrap, PCL-Au wrap, and PCL-Au + MSC wrap-on AVF …

Single-Cell Chromatin Accessibility Profiling Of Acute Myeloid Leukemia Reveals Heterogeneous Lineage Composition Upon Therapy-Resistance, Katarzyna Tomczak, Praveen Barrodia, Shaoheng Liang, Ken Chen, Linghua Wang, Zhongming Zhao, Kunal Rai, Abhinav K Jain, John Dick, Naval Daver, Andy Futreal, Hussein A Abbas

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by high rate of therapy resistance. Since the cell of origin can impact response to therapy, it is crucial to understand the lineage composition of AML cells at time of therapy resistance. Here we leverage single-cell chromatin accessibility profiling of 22 AML bone marrow aspirates from eight patients at time of therapy resistance and following subsequent therapy to characterize their lineage landscape. Our findings reveal a complex lineage architecture of therapy-resistant AML cells that are primed for stem and progenitor lineages and spanning quiescent, activated and late stem cell/progenitor states. Remarkably, …

Is Wedge A Dirty Word? Demographic And Facility-Level Variables Associated With High-Quality Wedge Resection, Micaela L. Collins, Greg L. Whitehorn, Shale J. Mack, Brian M. Till, Hamza Rshaidat, Tyler R. Grenda, Nathaniel R. Evans, Olugbenga T. Okusanya

Jefferson Hospital Staff Papers and Presentations

OBJECTIVES: Although sublobar resections have gained traction, wedge resections vary widely in quality. We seek to characterize the demographic and facility-level variables associated with high-quality wedge resections.

METHODS: The National Cancer Database was queried from 2010 to 2018. Patients with T1/T2 N0 M0 non-small cell lung cancer 2 cm or less who underwent wedge resection without neoadjuvant therapy were included. A wedge resection with no nodes sampled or with positive margins was categorized as a low-quality wedge. A wedge resection with 4 or more nodes sampled and negative margins was categorized as a high-quality wedge. Facility-specific variables were investigated via …

Measuring And Enhancing The Ionic Conductivity Of Chloroaluminate Electrolytes For Al-Ion Batteries, Anthony J Lucio, Iwan Sumarlan, Elena Bulmer, Igor Efimov, Stephen Viles, Christopher J Zaleski

Faculty, Staff and Student Publications

At the core of the aluminum (Al) ion battery is the liquid electrolyte, which governs the underlying chemistry. Optimizing the rheological properties of the electrolyte is critical to advance the state of the art. In the present work, the chloroaluminate electrolyte is made by reacting AlCl3 with a recently reported acetamidinium chloride (Acet-Cl) salt in an effort to make a more performant liquid electrolyte. Using AlCl3:Acet-Cl as a model electrolyte, we build on our previous work, which established a new method for extracting the ionic conductivity from fitting voltammetric data, and in this contribution, we validate the method across a …

Dynamic Mapping Of Proteome Trafficking Within And Between Living Cells By Transitid, James Messing, Brian D Freibaum, Steven Boeynaems, J Paul Taylor, Namrata D Udeshi, Steven A Carr, Alice Y Ting

Faculty, Staff and Students Publications

The ability to map trafficking for thousands of endogenous proteins at once in living cells would reveal biology currently invisible to both microscopy and mass spectrometry. Here, we report TransitID, a method for unbiased mapping of endogenous proteome trafficking with nanometer spatial resolution in living cells. Two proximity labeling (PL) enzymes, TurboID and APEX, are targeted to source and destination compartments, and PL with each enzyme is performed in tandem via sequential addition of their small-molecule substrates. Mass spectrometry identifies the proteins tagged by both enzymes. Using TransitID, we mapped proteome trafficking between cytosol and mitochondria, cytosol and nucleus, and …

Competencies For Psychology Practice In Pediatric Palliative Care, Aimee K Hildenbrand, Melissa K Cousino, Meghan L Marsac, Jill Majeski, Karen Wohlheiter, Rachel A Kentor

Faculty, Staff and Students Publications

Objective: Pediatric psychologists have unique expertise to contribute to the care of youth with serious illnesses yet are not routinely integrated into pediatric palliative care (PPC) teams. To better define the role and unique skillset of psychologists practicing in PPC, support their systematic inclusion as part of PPC teams, and advance trainee knowledge of PPC principles and skills, the PPC Psychology Working Group sought to develop core competencies for psychologists in this subspecialty.

Methods: A Working Group of pediatric psychologists with expertise in PPC met monthly to review literature and existing competencies in pediatrics, pediatric and subspecialty psychology, adult palliative …

Metastatic Infiltration Of Nervous Tissue And Periosteal Nerve Sprouting In Multiple Myeloma-Induced Bone Pain In Mice And Human, Marta Diaz-Delcastillo, Oana Palasca, Tim T Nemler, Didde M Thygesen, Norma A Chávez-Saldaña, Lizeth Y Ponce Gomez, Holly Evans, Rebecca E Andrews, Aritri Mandal, David Neves, Patrick Mehlen, James P Caruso, Patrick M Dougherty, Theodore J Price, Andrew Chantry, Michelle A Lawson, Thomas L Andersen, Juan M Jimenez-Andrade, Anne-Marie Heegaard

Faculty, Staff and Student Publications

Multiple myeloma (MM) is a neoplasia of B plasma cells that often induces bone pain. However, the mechanisms underlying myeloma-induced bone pain (MIBP) are mostly unknown. Using a syngeneic MM mouse model, we show that periosteal nerve sprouting of calcitonin gene-related peptide (CGRP+) and growth associated protein 43 (GAP43+) fibers occurs concurrent to the onset of nociception and its blockade provides transient pain relief. MM patient samples also showed increased periosteal innervation. Mechanistically, we investigated MM induced gene expression changes in the dorsal root ganglia (DRG) innervating the MM-bearing bone of male mice and found alterations in pathways associated with …