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Chronically Implanted Intracranial Electrodes: Tissue Reaction And Electrical Changes., Andrew Campbell, Chengyuan Wu Aug 2018

Chronically Implanted Intracranial Electrodes: Tissue Reaction And Electrical Changes., Andrew Campbell, Chengyuan Wu

Department of Neurosurgery Faculty Papers

The brain-electrode interface is arguably one of the most important areas of study in neuroscience today. A stronger foundation in this topic will allow us to probe the architecture of the brain in unprecedented functional detail and augment our ability to intervene in disease states. Over many years, significant progress has been made in this field, but some obstacles have remained elusive-notably preventing glial encapsulation and electrode degradation. In this review, we discuss the tissue response to electrode implantation on acute and chronic timescales, the electrical changes that occur in electrode systems over time, and strategies that are being investigated …


Lafora Disease Masquerading As Hepatic Dysfunction, Faisal Inayat, Waqas Ullah, Hanan T. Lodhi, Zarak H. Khan, Ghulam Ilyas, Nouman Safdar Ali, Hafez Mohammad A. Abdullah Aug 2018

Lafora Disease Masquerading As Hepatic Dysfunction, Faisal Inayat, Waqas Ullah, Hanan T. Lodhi, Zarak H. Khan, Ghulam Ilyas, Nouman Safdar Ali, Hafez Mohammad A. Abdullah

Abington Jefferson Health Papers

Lafora disease is fatal intractable progressive myoclonic epilepsy. It is frequently characterized by epileptic seizures, difficulty walking, muscle spasms, and dementia in late childhood or adolescence. We chronicle here an unusual case of an asymptomatic young male soccer player who presented with elevated liver enzymes. Neurological examination was unremarkable. The diagnostic workup for hepatitis, infectious etiologies, autoimmune disorders, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, and other related diseases was inconclusive. He subsequently underwent an uneventful percutaneous liver biopsy. Based on the pathognomonic histopathological findings, Lafora disease was considered the likely etiology. The present study is a unique illustration of this …


Examining Relationships Between Age At Diagnosis And Health-Related Quality Of Life Outcomes In Prostate Cancer Survivors., Christine J. Kurian, Amy Leader, Melissa S.Y. Thong, Scott W. Keith, Charnita Zeigler-Johnson Aug 2018

Examining Relationships Between Age At Diagnosis And Health-Related Quality Of Life Outcomes In Prostate Cancer Survivors., Christine J. Kurian, Amy Leader, Melissa S.Y. Thong, Scott W. Keith, Charnita Zeigler-Johnson

Department of Medical Oncology Faculty Papers

BACKGROUND: Patient reports of health related quality of life can provide important information about the long-term impact of prostate cancer. Because patient symptoms and function can differ by age of the survivor, the aim of our study was to examine patient-reported quality of life and prostate symptoms by age at diagnosis among a registry of Dutch prostate cancer survivors.

METHODS: A population of 617 individuals from the Patient Reported Outcomes Following Initial Treatment and Long-Term Evaluation of Survivorship (PROFILES) database was surveyed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) and prostate symptom …


Map7 Regulates Axon Morphogenesis By Recruiting Kinesin-1 To Microtubules And Modulating Organelle Transport., Stephen R. Tymanskyj, Benjamin Yang, Kristen J. Verhey, Le Ma Aug 2018

Map7 Regulates Axon Morphogenesis By Recruiting Kinesin-1 To Microtubules And Modulating Organelle Transport., Stephen R. Tymanskyj, Benjamin Yang, Kristen J. Verhey, Le Ma

Department of Neuroscience Faculty Papers

Neuronal cell morphogenesis depends on proper regulation of microtubule-based transport, but the underlying mechanisms are not well understood. Here, we report our study of MAP7, a unique microtubule-associated protein that interacts with both microtubules and the motor protein kinesin-1. Structure-function analysis in rat embryonic sensory neurons shows that the kinesin-1 interacting domain in MAP7 is required for axon and branch growth but not for branch formation. Also, two unique microtubule binding sites are found in MAP7 that have distinct dissociation kinetics and are both required for branch formation. Furthermore, MAP7 recruits kinesin-1 dynamically to microtubules, leading to alterations in organelle …


Consecutive Case Series Of Melanoma Sentinel Node Biopsy For Lymphoseek Compared To Sulfur Colloids, Caitlin Silvestri, Adrienne Christopher, Md, Charles Intenzo, Md, John C. Kairys, Md, Sung Kim, Md, Alliric Willis, Md, Adam C. Berger, Md Aug 2018

Consecutive Case Series Of Melanoma Sentinel Node Biopsy For Lymphoseek Compared To Sulfur Colloids, Caitlin Silvestri, Adrienne Christopher, Md, Charles Intenzo, Md, John C. Kairys, Md, Sung Kim, Md, Alliric Willis, Md, Adam C. Berger, Md

Department of Surgery Faculty Papers

Introduction: Sentinel lymph node biopsy (SLNB) is an important adjunct in the staging of patients with melanoma. Preoperative lymphoscintigraphy (LS) with radiolabeled isotopes is essential to localize sentinel nodes for removal. Our study compared the effectiveness of Lymphoseek to standard sulfur colloids (SC) in patients with melanoma undergoing SLNB.

Methods: We queried our IRB-approved melanoma database to identify 370 consecutive patients who underwent SLNB from 2012-2016 with at least one year of follow up. There were 185 patients in each group. Data points included characteristics of the primary melanoma lymphoscintigraphy, and SLNB. Student’s t-test and Chi-Square were used to analyze …


Lacrimal Gland Tumors In Turkey: Types, Frequency, And Outcomes., Yağmur Seda Yeşiltaş, Ahmet Kaan Gündüz, Esra Erden, Carol L. Shields Aug 2018

Lacrimal Gland Tumors In Turkey: Types, Frequency, And Outcomes., Yağmur Seda Yeşiltaş, Ahmet Kaan Gündüz, Esra Erden, Carol L. Shields

Wills Eye Hospital Papers

AIM: To evaluate the clinical, radiological, and treatment features of lacrimal gland tumors.

METHODS: Retrospective review of 99 eyes of 92 patients with lacrimal gland tumors diagnosed and managed in a single institution between January 1999 and March 2017. Clinical and radiological features, histopathology, treatment methods, and prognosis were evaluated.

RESULTS: The mean patient age was 40.3 (range: 7-80)y. The diagnosis was made histopathologically in 91 (91.9%) tumors and on a clinical and radiological basis in 8 (8.1%) tumors. Final diagnoses included idiopathic orbital inflammation (pseudotumor) in 46 (46.5%) lesions, pleomorphic adenoma in 14 (14.1%), adenoid cystic carcinoma in 12 …


Frameworks For Strategic Leadership, Larry Starr, Phd Aug 2018

Frameworks For Strategic Leadership, Larry Starr, Phd

School of Continuing and Professional Studies Faculty Papers

I suggest two frameworks that may improve understanding of strategic thinking, strategic decision making, and strategic leadership. The first I call the Epistemology Framework. The second which was described and continues to be promoted by David Snowdon and colleagues is the Cynefin Framework.


Development And Validation Of A Prostate Cancer Genomic Signature That Predicts Early Adt Treatment Response Following Radical Prostatectomy., R. Jeffrey Karnes, Vidit Sharma, Voleak Choeurng, Hussam Al-Deen Ashab, Nicholas Erho, Mohammed Alshalalfa, Bruce Trock, Ashley Ross, Kasra Yousefi, Harrison Tsai, Shuang G. Zhao, Jeffrey J. Tosoian, Zaid Haddad, Mandeep Takhar, S. Laura Chang, Daniel E. Spratt, Firas Abdollah, Robert B. Jenkins, Eric A. Klein, Paul L. Nguyen, Adam P. Dicker, Robert B. Den, Elai Davicioni, Felix Y. Feng, Tamara L. Lotan, Edward M. Schaeffer Aug 2018

Development And Validation Of A Prostate Cancer Genomic Signature That Predicts Early Adt Treatment Response Following Radical Prostatectomy., R. Jeffrey Karnes, Vidit Sharma, Voleak Choeurng, Hussam Al-Deen Ashab, Nicholas Erho, Mohammed Alshalalfa, Bruce Trock, Ashley Ross, Kasra Yousefi, Harrison Tsai, Shuang G. Zhao, Jeffrey J. Tosoian, Zaid Haddad, Mandeep Takhar, S. Laura Chang, Daniel E. Spratt, Firas Abdollah, Robert B. Jenkins, Eric A. Klein, Paul L. Nguyen, Adam P. Dicker, Robert B. Den, Elai Davicioni, Felix Y. Feng, Tamara L. Lotan, Edward M. Schaeffer

Department of Radiation Oncology Faculty Papers

Purpose: Currently, no genomic signature exists to distinguish men most likely to progress on adjuvant androgen deprivation therapy (ADT) after radical prostatectomy for high-risk prostate cancer. Here we develop and validate a gene expression signature to predict response to postoperative ADT.

Experimental Design: A training set consisting of 284 radical prostatectomy patients was established after 1:1 propensity score matching metastasis between adjuvant-ADT (a-ADT)-treated and no ADT–treated groups. An ADT Response Signature (ADT-RS) was identified from neuroendocrine and AR signaling–related genes. Two independent cohorts were used to form three separate data sets for validation (set I, n = 232; set II, …


The Role Of Human Papillomaviruses And Polyomaviruses In Braf-Inhibitor Induced Cutaneous Squamous Cell Carcinoma And Benign Squamoproliferative Lesions, Karin J. Purdie, Charlotte M. Proby, Hasan Rizvi, Heather Griffin, John Doorbar, Mary Sommerlad, Mariet C. Feltkamp, Els Van Der Meijden, Gareth J. Inman, Andrew P. South, Irene M. Leigh, Catherine A. Harwood Aug 2018

The Role Of Human Papillomaviruses And Polyomaviruses In Braf-Inhibitor Induced Cutaneous Squamous Cell Carcinoma And Benign Squamoproliferative Lesions, Karin J. Purdie, Charlotte M. Proby, Hasan Rizvi, Heather Griffin, John Doorbar, Mary Sommerlad, Mariet C. Feltkamp, Els Van Der Meijden, Gareth J. Inman, Andrew P. South, Irene M. Leigh, Catherine A. Harwood

Department of Dermatology and Cutaneous Biology Faculty Papers

Background: Human papillomavirus (HPV) has long been proposed as a cofactor in the pathogenesis of cutaneous squamous cell carcinoma (cSCC). More recently, the striking clinico-pathological features of cSCCs that complicate treatment of metastatic melanoma with inhibitors targeting BRAF mutations (BRAFi) has prompted speculation concerning a pathogenic role for oncogenic viruses. Here, we investigate HPV and human polyomaviruses (HPyV) and correlate with clinical, histologic, and genetic features in BRAFi-associated cSCC. Materials and Methods: Patients receiving BRAFi treatment were recruited at Barts Health NHS Trust. HPV DNA was detected in microdissected frozen samples using reverse line probe technology and degenerate and nested …


On The Dependability And Feasibility Of Layperson Ratings Of Divergent Thinking, Richard W. Hass, Marisa Rivera, Paul J. Silvia Aug 2018

On The Dependability And Feasibility Of Layperson Ratings Of Divergent Thinking, Richard W. Hass, Marisa Rivera, Paul J. Silvia

College of Humanities and Sciences Faculty Papers

A new system for subjective rating of responses to divergent thinking tasks was tested using raters recruited from Amazon Mechanical Turk. The rationale for the study was to determine if such raters could provide reliable (aka generalizable) ratings from the perspective of generalizability theory. To promote reliability across the Alternative Uses and Consequence task prompts often used by researchers as measures of Divergent Thinking, two parallel scales were developed to facilitate feasibility and validity of ratings performed by laypeople. Generalizability and dependability studies were conducted separately for two scoring systems: the average-rating system and the snapshot system. Results showed that …


Carnosol Modulates Th17 Cell Differentiation And Microglial Switch In Experimental Autoimmune Encephalomyelitis, Xing Li, Li Zhao, Juan-Juan Han, Fei Zhang, Shuai Liu, Lin Zhu, Zhe-Zhi Wang, Guang-Xian Zhang, Yuan Zhang Aug 2018

Carnosol Modulates Th17 Cell Differentiation And Microglial Switch In Experimental Autoimmune Encephalomyelitis, Xing Li, Li Zhao, Juan-Juan Han, Fei Zhang, Shuai Liu, Lin Zhu, Zhe-Zhi Wang, Guang-Xian Zhang, Yuan Zhang

Department of Neurology Faculty Papers

Medicinal plants as a rich pool for developing novel small molecule therapeutic medicine have been used for thousands of years. Carnosol as a bioactive diterpene compound originated from Rosmarinus officinalis (Rosemary) and Salvia officinalis, herbs extensively applied in traditional medicine for the treatment of multiple autoimmune diseases (1). In this study, we investigated the therapeutic effects and molecule mechanism of carnosol in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Carnosol treatment significantly alleviated clinical development in the myelin oligodendrocyte glycoprotein (MOG35–55) peptide-induced EAE model, markedly decreased inflammatory cell infiltration into the central nervous system and reduced …


The Conceptual Relevance Of Assessment Measures In Patients With Mild/Mild-Moderate Alzheimer's Disease, Ann Hartry, Natalie V.J. Aldhouse, Tamara Al-Zubeidi, Myrlene Sanon, Richard G. Stefanacci, Sarah L. Knight Aug 2018

The Conceptual Relevance Of Assessment Measures In Patients With Mild/Mild-Moderate Alzheimer's Disease, Ann Hartry, Natalie V.J. Aldhouse, Tamara Al-Zubeidi, Myrlene Sanon, Richard G. Stefanacci, Sarah L. Knight

College of Population Health Faculty Papers

Introduction: This study aims to evaluate the conceptual relevance of four measures of disease activity in patients with mild/mild-moderate Alzheimer's disease (AD): (1) the Alzheimer's Disease Assessment Scale–Cognitive Subscale; (2) the Alzheimer's Disease Cooperative Study–Activities of Daily Living Inventory; (3) the Neuropsychiatry Inventory; and (4) the Dependence Scale. Methods: A conceptual model depicting patient experience of mild AD was developed via literature review; concepts were compared with the items of the four measures. Relevance of the concepts included in the four measures was evaluated by patients with mild AD in a survey and follow-up interviews. Results: The four measures assessed …


Cannabis Shenanigans: Advocating For The Restoration Of An Effective Treatment Of Pain Following Spinal Cord Injury., Daniel E. Graves, Phd Aug 2018

Cannabis Shenanigans: Advocating For The Restoration Of An Effective Treatment Of Pain Following Spinal Cord Injury., Daniel E. Graves, Phd

Department of Rehabilitation Medicine Faculty Papers

Cannabis is an effective treatment for pain following spinal cord injury that should be available to patients and researchers. The major argument against the rescheduling of cannabis is that the published research is not convincing. This argument is disingenuous at best, given that the evidence has been presented and rejected at many points during the political dialog. Moreover, the original decision to criminalize cannabis did not utilize scientific or medical data. There is tension between the needs of a society to protect the vulnerable by restricting the rights of others to live well and with less pain. It is clear …


Determinants Of Successful Weight Loss In Low-Income African American Women: A Positive Deviance Analysis., Elaine Seaton Banerjee, Sharon J. Herring, Katelyn Hurley, Katherine Puskarz, Kyle Yebernetsky, Marianna Lanoue Aug 2018

Determinants Of Successful Weight Loss In Low-Income African American Women: A Positive Deviance Analysis., Elaine Seaton Banerjee, Sharon J. Herring, Katelyn Hurley, Katherine Puskarz, Kyle Yebernetsky, Marianna Lanoue

College of Population Health Faculty Papers

OBJECTIVE: We set out to investigate the behaviors of low-income African American women who successfully lost weight.

METHODS: From an urban, academic, family medicine practice, we used a mixed methods positive deviance approach to evaluate 35 low-income African American women who were obese and lost at least 10% of their maximum weight, and maintained this loss for 6 months, comparing them with 36 demographically similar control participants who had not lost weight. Survey outcomes included demographics and behaviors that were hypothesized to be related to successful weight loss. Interviews focused on motivations, barriers, and what made weight loss successful. Survey …


A-Type Kv Channels In Dorsal Root Ganglion Neurons: Diversity, Function, And Dysfunction, Benjamin M. Zemel, David M. Ritter, Manuel Covarrubias, Tanziyah Muqeem Aug 2018

A-Type Kv Channels In Dorsal Root Ganglion Neurons: Diversity, Function, And Dysfunction, Benjamin M. Zemel, David M. Ritter, Manuel Covarrubias, Tanziyah Muqeem

Department of Neuroscience Faculty Papers

A-type voltage-gated potassium (Kv) channels are major regulators of neuronal excitability that have been mainly characterized in the central nervous system. By contrast, there is a paucity of knowledge about the molecular physiology of these Kv channels in the peripheral nervous system, including highly specialized and heterogenous dorsal root ganglion (DRG) neurons. Although all A-type Kv channels display pore-forming subunits with similar structural properties and fast inactivation, their voltage-, and time-dependent properties and modulation are significantly different. These differences ultimately determine distinct physiological roles of diverse A-type Kv channels, and how their dysfunction might contribute to neurological disorders. The importance …


The Guanylate Cyclase C-Cgmp Signaling Axis Opposes Intestinal Epithelial Injury And Neoplasia., Jeffrey A. Rappaport, Scott A. Waldman Aug 2018

The Guanylate Cyclase C-Cgmp Signaling Axis Opposes Intestinal Epithelial Injury And Neoplasia., Jeffrey A. Rappaport, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Guanylate cyclase C (GUCY2C) is a transmembrane receptor expressed on the luminal aspect of the intestinal epithelium. Its ligands include bacterial heat-stable enterotoxins responsible for traveler's diarrhea, the endogenous peptide hormones uroguanylin and guanylin, and the synthetic agents, linaclotide, plecanatide, and dolcanatide. Ligand-activated GUCY2C catalyzes the synthesis of intracellular cyclic GMP (cGMP), initiating signaling cascades underlying homeostasis of the intestinal epithelium. Mouse models of GUCY2C ablation, and recently, human populations harboring GUCY2C mutations, have revealed the diverse contributions of this signaling axis to epithelial health, including regulating fluid secretion, microbiome composition, intestinal barrier integrity, epithelial renewal, cell cycle progression, responses …


Co-Use Of Tobacco And Marijuana During Pregnancy: Pathways To Externalizing Behavior Problems In Early Childhood., Stephanie A. Godleski, Shannon Shisler, Rina D. Eiden, Marilyn A. Huestis Aug 2018

Co-Use Of Tobacco And Marijuana During Pregnancy: Pathways To Externalizing Behavior Problems In Early Childhood., Stephanie A. Godleski, Shannon Shisler, Rina D. Eiden, Marilyn A. Huestis

Institute of Emerging Health Professions Faculty Papers

Use and co-use of tobacco and marijuana during pregnancy are associated with the development of social, cognitive, and behavioral problems for infants and children. However, less is known about the potential developmental impact of the use of tobacco and marijuana in tandem. The present study examined an etiological model for the development of externalizing behavior problems (EBP) in early childhood in a high risk sample (N = 247) of mother-infant dyads with prospective data from pregnancy to 36 months of child age. Co-use during pregnancy and continued maternal tobacco and marijuana use from infancy through early childhood were investigated. Although …


Modeling The Dynamics Of Human Liver Failure Post Liver Resection, Babita Verma, Pushpavanam Subramaniam, Rajanikanth Vadigepalli Aug 2018

Modeling The Dynamics Of Human Liver Failure Post Liver Resection, Babita Verma, Pushpavanam Subramaniam, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Liver resection is an important clinical intervention to treat liver disease. Following liver resection, patients exhibit a wide range of outcomes including normal recovery, suppressed recovery, or liver failure, depending on the regenerative capacity of the remnant liver. The objective of this work is to study the distinct patient outcomes post hepatectomy and determine the processes that are accountable for liver failure. Our model based approach shows that cell death is one of the important processes but not the sole controlling process responsible for liver failure. Additionally, our simulations showed wide variation in the timescale of liver failure that is …


Gamification Of Hospital Utilization: Incorporating Cost-Consciousness In Daily Practices., Peter J Tomaselli, Dimitrios Papanagnou, Md, Jonathan E Karademos, Elizabeth Teixeira, Xiao Chi Zhang Aug 2018

Gamification Of Hospital Utilization: Incorporating Cost-Consciousness In Daily Practices., Peter J Tomaselli, Dimitrios Papanagnou, Md, Jonathan E Karademos, Elizabeth Teixeira, Xiao Chi Zhang

Department of Emergency Medicine Faculty Papers

Healthcare costs in the United States have skyrocketed over the past decade, contributing to an estimated $750 billion in wasteful spending annually. Despite the demand to improve residency education on value-based, cost-conscious healthcare, there is no consensus on how to best teach this practice. Traditional lectures have failed to demonstrate enduring change in clinical practice patterns, provider attitudes, and reductions in hospital expenditures. We sought to evaluate whether gamification is an effective pedagogical tool to teach cost-consciousness to emergency medicine (EM) residents by creating a 60-minute interactive session based on the popular gameshow, the Price is Right. Costs and associated …


Endorepellin Remodels The Endothelial Transcriptome Toward A Pro-Autophagic And Pro-Mitophagic Gene Signature., Thomas Neill, Eva Andreuzzi, Zi-Xuan Wang, Stephen C. Peiper, Maurizo Mongiat, Renato V. Iozzo Aug 2018

Endorepellin Remodels The Endothelial Transcriptome Toward A Pro-Autophagic And Pro-Mitophagic Gene Signature., Thomas Neill, Eva Andreuzzi, Zi-Xuan Wang, Stephen C. Peiper, Maurizo Mongiat, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Regulation of autophagy by proteolytically cleaved fragments of heparan sulfate proteoglycans is a novel and current research focus in tumor biology. Endorepellin is the C-terminal angiostatic fragment of the heparan sulfate proteoglycan perlecan and induces autophagy in endothelial cells. To further investigate this property, we used NanoString, a digital PCR platform for measuring pre-defined transcripts in biological samples to analyze a custom subset of 95 autophagy-related genes in human umbilical vein endothelial cells treated with ultrapure human recombinant endorepellin. We discovered an endorepellin-evoked pro-autophagic and pro-mitophagic gene expression signatures, which included two coordinately up-regulated mitochondrial-associated genes encoding the E3 ubiquitin …


Left Ventricular Pseudoaneurysm: An Overview Of Diagnosis And Management., Faisal Inayat, Ali Raza Ghani, Iqra Riaz, Nouman Safdar Ali, Usman Sarwar, Raphael Bonita, Hafeez Ul Hassan Virk Aug 2018

Left Ventricular Pseudoaneurysm: An Overview Of Diagnosis And Management., Faisal Inayat, Ali Raza Ghani, Iqra Riaz, Nouman Safdar Ali, Usman Sarwar, Raphael Bonita, Hafeez Ul Hassan Virk

Abington Jefferson Health Papers

Left ventricular pseudoaneurysm is a rare but life-threatening disorder that is frequently reported secondary to myocardial infarction or cardiac surgery. In this article, we chronicle the case of a patient with no prior risk factors who presented with a 2-week history of nonexertional atypical left chest pain. Apical 2-chamber transthoracic echocardiography revealed an unexpected outpouching of basal inferoseptal wall of the left ventricle, which had a narrow neck and relatively wide apex. The patient was diagnosed with left ventricular pseudoaneurysm and medical therapy was initiated. He refused to undergo the surgical intervention and subsequently, he was discharged from the hospital …


An Approach To Identify A Minimum And Rational Proportion Of Caesarean Sections In Resource-Poor Settings: A Global Network Study., José M. Belizán, Nicole Minckas, Elizabeth M. Mcclure, Sarah Saleem, Janet L. Moore, Shivaprasad S. Goudar, Fabian Esamai, Archana Patel, Elwyn Chomba, Ana L. Garces, Fernando Althabe, Margo S. Harrison, Nancy F. Krebs, Richard Derman, Waldemar A. Carlo, Edward A. Liechty, Patricia L. Hibberd, Pierre M. Buekens, Robert L. Goldenberg Aug 2018

An Approach To Identify A Minimum And Rational Proportion Of Caesarean Sections In Resource-Poor Settings: A Global Network Study., José M. Belizán, Nicole Minckas, Elizabeth M. Mcclure, Sarah Saleem, Janet L. Moore, Shivaprasad S. Goudar, Fabian Esamai, Archana Patel, Elwyn Chomba, Ana L. Garces, Fernando Althabe, Margo S. Harrison, Nancy F. Krebs, Richard Derman, Waldemar A. Carlo, Edward A. Liechty, Patricia L. Hibberd, Pierre M. Buekens, Robert L. Goldenberg

Global Health Articles

BACKGROUND: Caesarean section prevalence is increasing in Asia and Latin America while remaining low in most African regions. Caesarean section delivery is effective for saving maternal and infant lives when they are provided for medically-indicated reasons. On the basis of ecological studies, caesarean delivery prevalence between 9% and 19% has been associated with better maternal and perinatal outcomes, such as reduced maternal land fetal mortality. However, the specific prevalence of obstetric and medical complications that require caesarean section have not been established, especially in low-income and middle-income countries (LMICs). We sought to provide information to inform the approach to the …


Syntaphilin Ubiquitination Regulates Mitochondrial Dynamics And Tumor Cell Movements., Jae Ho Seo, Ekta Agarwal, Kelly G. Bryant, M. Cecilia Caino, Eui Tae Kim, Andrew V. Kossenkov, Hsin-Yao Tang, Lucia R. Languino, Dmitry I. Gabrilovich, Andrew R. Cohen, David W. Speicher, Dario C. Altieri Aug 2018

Syntaphilin Ubiquitination Regulates Mitochondrial Dynamics And Tumor Cell Movements., Jae Ho Seo, Ekta Agarwal, Kelly G. Bryant, M. Cecilia Caino, Eui Tae Kim, Andrew V. Kossenkov, Hsin-Yao Tang, Lucia R. Languino, Dmitry I. Gabrilovich, Andrew R. Cohen, David W. Speicher, Dario C. Altieri

Department of Cancer Biology Faculty Papers

Syntaphilin (SNPH) inhibits the movement of mitochondria in tumor cells, preventing their accumulation at the cortical cytoskeleton and limiting the bioenergetics of cell motility and invasion. Although this may suppress metastasis, the regulation of the SNPH pathway is not well understood. Using a global proteomics screen, we show that SNPH associates with multiple regulators of ubiquitin-dependent responses and is ubiquitinated by the E3 ligase CHIP (or STUB1) on Lys111 and Lys153 in the microtubule-binding domain. SNPH ubiquitination did not result in protein degradation, but instead anchored SNPH on tubulin to inhibit mitochondrial motility and cycles of organelle fusion and fission, …


High Fat Diet Upregulates Fatty Acid Oxidation And Ketogenesis Via Intervention Of Ppar-Γ., Kunal Sikder, Sanket Kumar Shukla, Neel Patel, Harpreet Singh, Khadija Rafiq Aug 2018

High Fat Diet Upregulates Fatty Acid Oxidation And Ketogenesis Via Intervention Of Ppar-Γ., Kunal Sikder, Sanket Kumar Shukla, Neel Patel, Harpreet Singh, Khadija Rafiq

Center for Translational Medicine Faculty Papers

BACKGROUND/AIMS: Systemic hyperlipidemia and intracellular lipid accumulation induced by chronic high fat diet (HFD) leads to enhanced fatty acid oxidation (FAO) and ketogenesis. The present study was aimed to determine whether activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) by surplus free fatty acids (FA) in hyperlipidemic condition, has a positive feedback regulation over FAO and ketogenic enzymes controlling lipotoxicity and cardiac apoptosis.

METHODS: 8 weeks old C57BL/6 wild type (WT) or PPAR-γ-/- mice were challenged with 16 weeks 60% HFD to induce obesity mediated type 2 diabetes mellitus (T2DM) and diabetic cardiomyopathy. Treatment course was followed by echocardiographic measurements, glycemic and …


Visual Field Changes In Professional Wind Versus Non-Wind Musical Instrument Players In The Philadelphia Orchestra, Shuai‑Chun Lin, Cindy X. Zheng, Michael Waisbourd, Jeanne Molineaux, Lichuan Zeng, Tingting Zhan, Kamran Rahmatnejad, Arthur Resende, Anand V. Mantravadi, Lisa A. Hark, Marlene R. Moster, Joseph I. Markoff, George L. Spaeth, L. Jay Katz Aug 2018

Visual Field Changes In Professional Wind Versus Non-Wind Musical Instrument Players In The Philadelphia Orchestra, Shuai‑Chun Lin, Cindy X. Zheng, Michael Waisbourd, Jeanne Molineaux, Lichuan Zeng, Tingting Zhan, Kamran Rahmatnejad, Arthur Resende, Anand V. Mantravadi, Lisa A. Hark, Marlene R. Moster, Joseph I. Markoff, George L. Spaeth, L. Jay Katz

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Purpose: We compare the prevalence of glaucoma in professional wind versus non‑wind instrument players in the Philadelphia Orchestra. Visual field changes in individuals with glaucoma and glaucoma suspects were evaluated, and the results were correlated with cumulative practice time. Methods: In this cross‑sectional, observational study, fifty‑one Philadelphia Orchestra musicians were enrolled and categorized as wind or non‑wind instrument players. All study participants underwent screening fundus photography. Participants with optic discs suspicious for glaucoma underwent further evaluation, including standard automated visual field perimetry and a comprehensive eye examination by a glaucoma specialist. Results: Of the 51 musicians enrolled, 9 of …


Myocardial Dysfunction After Out-Of-Hospital Cardiac Arrest: Predictors And Prognostic Implications., Yuan Yao, Nicholas James Johnson, Sarah Muirhead Perman, Vimal Ramjee, Anne Victoria Grossestreuer, David Foster Gaieski Aug 2018

Myocardial Dysfunction After Out-Of-Hospital Cardiac Arrest: Predictors And Prognostic Implications., Yuan Yao, Nicholas James Johnson, Sarah Muirhead Perman, Vimal Ramjee, Anne Victoria Grossestreuer, David Foster Gaieski

Department of Emergency Medicine Faculty Papers

We aim to determine the incidence of early myocardial dysfunction after out-of-hospital cardiac arrest, risk factors associated with its development, and association with outcome. A retrospective chart review was performed among consecutive out-of-hospital cardiac arrest (OHCA) patients who underwent echocardiography within 24 h of return of spontaneous circulation at three urban teaching hospitals. Our primary outcome is early myocardial dysfunction, defined as a left ventricular ejection fraction < 40% on initial echocardiogram. We also determine risk factors associated with myocardial dysfunction using multivariate analysis, and examine its association with survival and neurologic outcome. A total of 190 patients achieved ROSC and underwent echocardiography within 24 h. Of these, 83 (44%) patients had myocardial dysfunction. A total of 37 (45%) patients with myocardial dysfunction survived to discharge, 39% with intact neurologic status. History of congestive heart failure (OR 6.21; 95% CI 2.54-15.19), male gender (OR 2.27; 95% CI 1.08-4.78), witnessed arrest (OR 4.20; 95% CI 1.78-9.93), more than three doses of epinephrine (OR 6.10; 95% CI 1.12-33.14), more than four defibrillations (OR 4.7; 95% CI 1.35-16.43), longer duration of resuscitation (OR 1.06; 95% CI 1.01-1.10), and therapeutic hypothermia (OR 3.93; 95% CI 1.32-11.75) were associated with myocardial dysfunction. Cardiopulmonary resuscitation immediately initiated by healthcare personnel was associated with lower odds of myocardial dysfunction (OR 0.40; 95% CI 0.17-0.97). There was no association between early myocardial dysfunction and mortality or neurological outcome. Nearly half of OHCA patients have myocardial dysfunction. A number of clinical factors are associated with myocardial dysfunction, and may aid providers in anticipating which patients need early diagnostic evaluation and specific treatments. Early myocardial dysfunction is not associated with neurologically intact survival.


Enhanced Co-Registration Methods To Improve Intracranial Electrode Contact Localization., Walter A. Hinds, Amrit Misra, Michael R. Sperling, Ashwini Sharan, Joseph I. Tracy, Karen A. Moxon Aug 2018

Enhanced Co-Registration Methods To Improve Intracranial Electrode Contact Localization., Walter A. Hinds, Amrit Misra, Michael R. Sperling, Ashwini Sharan, Joseph I. Tracy, Karen A. Moxon

Department of Neurology Faculty Papers

Background: Electrode contact locations are important when planning tailored brain surgeries to identify pathological tissue targeted for resection and conversely avoid eloquent tissue. Current methods employ trained experts to use neuroimaging scans that are manually co-registered and localize contacts within ~2 mm. Yet, the state of the art is limited by either the expertise needed for each type of intracranial electrode or the inter-modality co-registration which increases error, reducing accuracy. Patients often have a variety of strips, grids and depths implanted; therefore, it is cumbersome and time-consuming to apply separate localization methods for each type of electrode, requiring expertise across …


Quantitative Assessment Of The Anatomical Footprint Of The C1 Pedicle Relative To The Lateral Mass: A Guide For C1 Lateral Mass Fixation, Brian W. Su, Alexander A. Theologis, Robert H. Byers, Adam L. Shimer, Gregory D. Schroeder, Alexander R. Vaccaro, Bobby Tay Aug 2018

Quantitative Assessment Of The Anatomical Footprint Of The C1 Pedicle Relative To The Lateral Mass: A Guide For C1 Lateral Mass Fixation, Brian W. Su, Alexander A. Theologis, Robert H. Byers, Adam L. Shimer, Gregory D. Schroeder, Alexander R. Vaccaro, Bobby Tay

Rothman Institute Papers

Study Design: Anatomic study. Objectives: To determine the relationship of the anatomical footprint of the C1 pedicle relative to the lateral mass (LM). Methods: Anatomic measurements were made on fresh frozen human cadaveric C1 specimens: pedicle width/height, LM width/height (minimum/maximum), LM depth, distance between LM’s medial aspect and pedicle’s medial border, distance between LM’s lateral aspect to pedicle’s lateral border, distance between pedicle’s inferior aspect and LM’s inferior border, distance between arch’s midline and pedicle’s medial border. The percentage of LM medial to the pedicle and the distance from the center of the LM to the pedicle’s medial wall were …


Activation Of The Gi Protein-Rhoa Axis By Non-Canonical Hedgehog Signaling Is Independent Of Primary Cilia., Lan Ho Wei, Mohammad Arastoo, Ioanna Georgiou, David R. Manning, Natalia A. Riobo-Del Galdo Aug 2018

Activation Of The Gi Protein-Rhoa Axis By Non-Canonical Hedgehog Signaling Is Independent Of Primary Cilia., Lan Ho Wei, Mohammad Arastoo, Ioanna Georgiou, David R. Manning, Natalia A. Riobo-Del Galdo

Department of Biochemistry and Molecular Biology Faculty Papers

Primary cilia are solitary organelles that emanate from the plasma membrane during growth arrest in almost all mammalian cells. The canonical Hedgehog (HH) pathway requires trafficking of the G protein-coupled receptor SMOOTHENED (SMO) and the GLI transcription factors to the primary cilium upon binding of a HH ligand to PATCHED1. However, it is unknown if activation of the small GTPase RHOA by SMO coupling to heterotrimeric Gi proteins, a form of non-canonical HH signaling, requires localization of SMO in the primary cilium. In this study, we compared RHOA and Gi protein stimulation by activation of SMO or sphingosine 1-phosphate receptor …


Trans-Lymphatic Contrast-Enhanced Ultrasound In Combination With Blue Dye Injection Is Feasible For Detection And Biopsy Of Sentinel Lymph Nodes In Breast Cancer, Xiangmei Chen, Md, Jieyu Zhong, Md, Zhengming Hu, Md, Wei Wei, Md, Weihua Yin, Md, Ligang Cui, Md, Ji-Bin Liu, Md, Desheng Sun, Md Aug 2018

Trans-Lymphatic Contrast-Enhanced Ultrasound In Combination With Blue Dye Injection Is Feasible For Detection And Biopsy Of Sentinel Lymph Nodes In Breast Cancer, Xiangmei Chen, Md, Jieyu Zhong, Md, Zhengming Hu, Md, Wei Wei, Md, Weihua Yin, Md, Ligang Cui, Md, Ji-Bin Liu, Md, Desheng Sun, Md

Department of Radiology Faculty Papers

Objective: The best method for sentinel lymph node biopsy (SLNB) in early-staged breast cancer (EBC) remains controversial. This study aimed to evaluate a novel method by combining trans-lymphatic contrast-enhanced ultrasound (TLCEUS) with blue dye injection as a guidance of SLNB.

Methods: TLCEUS was performed in 88 patients with newly diagnosed EBC. Methylene blue dye was percutaneously injected into enhanced sentinel lymph nodes (SLNs) under ultrasound guidance, followed by standard SLNB and axillary lymph node dissection. Enhancement patterns and the arriving time (AT) of contrast agent within SLNs were evaluated. Histopathological examination of dissected nodes was performed to confirm metastasis.

Results: …