Analytical, Diagnostic and Therapeutic Techniques and Equipment Commons^™

Decorin Suppresses Tumor Lymphangiogenesis: A Mechanism To Curtail Cancer Progression, Dipon K. Mondal, Christopher Xie, Gabriel J. Pascal, Simone Buraschi, Renato V. Iozzo

Kimmel Cancer Center Faculty Papers

The complex interplay between malignant cells and the cellular and molecular components of the tumor stroma is a key aspect of cancer growth and development. These tumor-host interactions are often affected by soluble bioactive molecules such as proteoglycans. Decorin, an archetypical small leucine-rich proteoglycan primarily expressed by stromal cells, affects cancer growth in its soluble form by interacting with several receptor tyrosine kinases (RTK). Overall, decorin leads to a context-dependent and protracted cessation of oncogenic RTK activity by attenuating their ability to drive a prosurvival program and to sustain a proangiogenic network. Through an unbiased transcriptomic analysis using deep RNAseq, …

Non-Thermal Plasma Reduces Hsv-1 Infection Of And Replication In Hacat Keratinocytes In Vitro, Julia Sutter, Jascha Brettschneider, Brian Wigdahl, Peter Bruggeman, Fred Krebs, Vandana Miller

Kimmel Cancer Center Faculty Papers

Herpes simplex virus type 1 (HSV-1) is a lifelong pathogen characterized by asymptomatic latent infection in the trigeminal ganglia (TG), with periodic outbreaks of cold sores caused by virus reactivation in the TG and subsequent replication in the oral mucosa. While antiviral therapies can provide relief from cold sores, they are unable to eliminate HSV-1. We provide experimental results that highlight non-thermal plasma (NTP) as a new alternative therapy for HSV-1 infection that would resolve cold sores faster and reduce the establishment of latent infection in the TG. Additionally, this study is the first to explore the use of NTP …

Hsp70 Is A Critical Regulator Of Hsp90 Inhibitor's Effectiveness In Preventing Hcl-Induced Chronic Lung Injury And Pulmonary Fibrosis, Ruben M. L. Colunga Biancatelli, Pavel A. Solopov, Tierney Day, Betsy Gregory, Michael Osei-Nkansah, Christiana Dimitropoulou, John D. Catravas

Bioelectrics Publications

Exposure to hydrochloric acid (HCl) can provoke acute and chronic lung injury. Because of its extensive production for industrial use, frequent accidental exposures occur, making HCl one of the top five chemicals causing inhalation injuries. There are no Food and Drug Administration (FDA)-approved treatments for HCl exposure. Heat shock protein 90 (HSP90) inhibitors modulate transforming growth factor-β (TGF-β) signaling and the development of chemical-induced pulmonary fibrosis. However, little is known on the role of Heat Shock Protein 70 (HSP70) during injury and treatment with HSP90 inhibitors. We hypothesized that administration of geranylgeranyl-acetone (GGA), an HSP70 inducer, or gefitinib (GFT), an …

Serotonin Reduction In Post-Acute Sequelae Of Viral Infection, Andrea Wong, Ashwarya Devason, Iboro Umana, Timothy Cox, Lenka Dohnalová, Lev Litichevskiy, Jonathan Perla, Patrick Lundgren, Zienab Etwebi, Luke Izzo, Jihee Kim, Monika Tetlak, Hélène Descamps, Simone Park, Stephen Wisser, Aaron Mcknight, Ryan Pardy, Junwon Kim, Niklas Blank, Shaan Patel, Katharina Thum, Sydney Mason, Jean-Christophe Beltra, Michaël Michieletto, Shin Foong Ngiow, Brittany Miller, Megan Liou, Bhoomi Madhu, Oxana Dmitrieva-Posocco, Alex Huber, Peter Hewins, Christopher Petucci, Candice Chu, Gwen Baraniecki-Zwil, Leila Giron, Amy Baxter, Allison Greenplate, Charlotte Kearns, Kathleen Montone, Leslie Litzky, Michael Feldman, Jorge Henao-Mejia, Boris Striepen, Holly Ramage, Kellie Jurado, Kathryn Wellen, Una O'Doherty, Mohamed Abdel-Mohsen, Alan L Landay, Ali Keshavarzian, Timothy Henrich, Steven Deeks, Michael Peluso, Nuala Meyer, E. John Wherry, Benjamin Abramoff, Sara Cherry, Christoph Thaiss, Maayan Levy

Department of Microbiology and Immunology Faculty Papers

Post-acute sequelae of COVID-19 (PASC, "Long COVID") pose a significant global health challenge. The pathophysiology is unknown, and no effective treatments have been found to date. Several hypotheses have been formulated to explain the etiology of PASC, including viral persistence, chronic inflammation, hypercoagulability, and autonomic dysfunction. Here, we propose a mechanism that links all four hypotheses in a single pathway and provides actionable insights for therapeutic interventions. We find that PASC are associated with serotonin reduction. Viral infection and type I interferon-driven inflammation reduce serotonin through three mechanisms: diminished intestinal absorption of the serotonin precursor tryptophan; platelet hyperactivation and thrombocytopenia, …

Self-Administered Intranasal Etripamil Using A Symptom-Prompted, Repeat-Dose Regimen For Atrioventricular-Nodal-Dependent Supraventricular Tachycardia (Rapid): A Multicentre, Randomised Trial, Bruce S Stambler, A John Camm, Marco Alings, Paul Dorian, Hein Heidbuchel, Jaco Houtgraaf, Peter R. Kowey, Jose L Merino, Blandine Mondésert, Jonathan P Piccini, Sean D Pokorney, Philip T Sager, Atul Verma, J Marcus Wharton, David B Bharucha, Francis Plat, Silvia Shardonofsky, Michael Chen, James E Ip

Department of Medicine Faculty Papers

BACKGROUND: Etripamil is a fast-acting, intranasally administered calcium-channel blocker in development for on-demand therapy outside a health-care setting for paroxysmal supraventricular tachycardia. We aimed to evaluate the efficacy and safety of etripamil 70 mg nasal spray using a symptom-prompted, repeat-dose regimen for acute conversion of atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia to sinus rhythm within 30 min.

METHODS: RAPID was a multicentre, randomised, placebo-controlled, event-driven trial, conducted at 160 sites in North America and Europe as part 2 of the NODE-301 study. Eligible patients were aged at least 18 years and had a history of paroxysmal supraventricular tachycardia with sustained, symptomatic episodes …

Scutellaria Baicalensis Enhances 5-Fluorouracil-Based Chemotherapy Via Inhibition Of Proliferative Signaling Pathways, Haizhou Liu, Hui Liu, Zhiyi Zhou, Jessica Chung, Guojing Zhang, Jin Chang, Robert A Parise, Edward Chu, John C Schmitz

Abington Jefferson Health Papers

Fluoropyridine-based chemotherapy remains the most widely used treatment for colorectal cancer (CRC). In this study, we investigated the mechanism by which the natural product Scutellaria baicalensis (Huang Qin; HQ) and one of its main components baicalin enhanced 5-fluorouracil (5-FU) antitumor activity against CRC. Cell proliferation assays, cell cycle analysis, reverse-phase protein array (RPPA) analysis, immunoblot analysis, and qRT-PCR were performed to investigate the mechanism(s) of action of HQ and its active components on growth of CRC cells. HQ exhibited in vitro antiproliferative activity against drug resistant human CRC cells, against human and mouse CRC cells with different genetic backgrounds and …

Successful Buprenorphine Transition While Overlapping With A Full Opioid Agonist To Treat Chronic Pain: A Case Report, Kishan V. Patel, Sidharth Sahni, Lanvin F. Taylor

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Buprenorphine is a partial mu opioid agonist that has been increasingly utilized to treat patients with chronic pain and opioid use disorder (OUD). The drug has proven to provide significant chronic pain relief at low doses ranging from 75 to 1800 mcg. The conventional buprenorphine transitional process delays its introduction until patients begin withdrawal. However, this process can pose a barrier to both patients and providers due to some patients' inability to tolerate traditional prerequisite withdrawal. To our knowledge, this is a rare reported case to describe a transitional process utilizing buccal buprenorphine in which a patient with chronic pain …

Outbreak Of Ebola Virus Disease, Alexandra Dimit, Tiffany Kneuss, Joelle Farano, Haley Armstrong, Jodi Otte, Andrew M. Roecker

Pharmacy and Wellness Review

Ebola virus disease (EVD) has existed as a major health concern with devastating and, many times, fatal symptoms. The recent outbreaks of EVD in West Africa and the Democratic Republic of the Congo (DRC) have incited international concern. In this article, the implications of EVD will be discussed including the etiology, transmission, signs and symptoms, diagnosis and treatment of the disease. In addition to this discussion, the manner in which major health care organizations, including the World Health Organization (WHO), are dealing with treating infected patients and containing spread of the disease will be covered.

Genomic Prediction Of Relapse In Recipients Of Allogeneic Haematopoietic Stem Cell Transplantation., J Ritari, K Hyvärinen, S Koskela, M Itälä-Remes, R Niittyvuopio, A Nihtinen, U Salmenniemi, M Putkonen, L Volin, T Kwan, T Pastinen, J Partanen

Manuscripts, Articles, Book Chapters and Other Papers

Allogeneic haematopoietic stem cell transplantation currently represents the primary potentially curative treatment for cancers of the blood and bone marrow. While relapse occurs in approximately 30% of patients, few risk-modifying genetic variants have been identified. The present study evaluates the predictive potential of patient genetics on relapse risk in a genome-wide manner. We studied 151 graft recipients with HLA-matched sibling donors by sequencing the whole-exome, active immunoregulatory regions, and the full MHC region. To assess the predictive capability and contributions of SNPs and INDELs, we employed machine learning and a feature selection approach in a cross-validation framework to discover the …

Incidence Of Acute Kidney Injury Among Patients Treated With Piperacillin-Tazobactam Or Meropenem In Combination With Vancomycin, Wilbur Cliff Rutter, David S. Burgess

Pharmacy Practice and Science Faculty Publications

Acute kidney injury (AKI) increases during empirical antimicrobial therapy with the combination of piperacillin-tazobactam (TZP) and vancomycin (VAN) compared to the number of incidences with monotherapy or the combination of cefepime and VAN. Limited data regarding the impact of meropenem (MEM) combined with VAN exist. This study examined the AKI incidence among patients treated with MEM plus VAN (MEM+VAN) or TZP+VAN. Data were collected from the University of Kentucky Center for Clinical and Translational Science Enterprise Data Trust from September 2007 through October 2015. Adults without previous renal disease who received MEM+VAN or TZP+VAN for at least 2 days were …

Genetic Variants In Hsd17b3, Smad3, And Ipo11 Impact Circulating Lipids In Response To Fenofibrate In Individuals With Type 2 Diabetes, Daniel M. Rotroff, Sonja S. Pijut, Skylar W. Marvel, John R. Jack, Tammy M. Havener, Aurora Pujol, Agatha Schluter, Gregory A. Graf, Henry N. Ginsberg, Hetal S. Shah, He Gao, Mario-Luca Morieri, Alessandro Doria, Josyf C. Mychaleckyi, Howard L. Mcleod, John B. Buse, Michael J. Wagner, Alison A. Motsinger-Reif, Accord/Accordion Investigators

Pharmaceutical Sciences Faculty Publications

Individuals with type 2 diabetes (T2D) and dyslipidemia are at an increased risk of cardiovascular disease. Fibrates are a class of drugs prescribed to treat dyslipidemia, but variation in response has been observed. To evaluate common and rare genetic variants that impact lipid responses to fenofibrate in statin‐treated patients with T2D, we examined lipid changes in response to fenofibrate therapy using a genomewide association study (GWAS). Associations were followed‐up using gene expression studies in mice. Common variants in SMAD3 and IPO11 were marginally associated with lipid changes in black subjects (P < 5 × 10^‐6). Rare variant and gene expression changes …

Sustained Sensitizing Effects Of Tumor Necrosis Factor Alpha On Sensory Nerves In Lung And Airways, Ruei-Lung Lin, Qihai Gu, Mehdi Khosravi, Lu-Yuan Lee

Physiology Faculty Publications

Tumor necrosis factor alpha (TNFα) plays a significant role in the pathogenesis of airway inflammatory diseases. Inhalation of aerosolized TNFα induced airway hyperresponsiveness accompanied by airway inflammation in healthy human subjects, but the underlying mechanism is not fully understood. We recently reported a series of studies aimed to investigate if TNFα elevates the sensitivity of vagal bronchopulmonary sensory nerves in a mouse model; these studies are summarized in this mini-review. Our results showed that intratracheal instillation of TNFα induced pronounced airway inflammation 24 hours later, as illustrated by infiltration of eosinophils and neutrophils and the release of inflammatory mediators and …

Understanding The Patient Experience With Carcinoid Syndrome: Exit Interviews From A Randomized, Placebo-Controlled Study Of Telotristat Ethyl, Lowell B. Anthony, Claire Ervin, Pablo Lapuerta, Matthew H. Kulke, Pamela Kunz, Emily Bergsland, Dieter Hörsch, David C. Metz, Janice Pasieka, Nick Pavlakis, Marianne Pavel, Martyn Caplin, Kjell Öberg, John Ramage, Emily Evans, Qi Melissa Yang, Shanna Jackson, Karie Arnold, Linda Law, Dana B. Dibenedetti

Markey Cancer Center Faculty Publications

Purpose: Telotristat ethyl, an oral tryptophan hydroxylase inhibitor, is intended to treat carcinoid syndrome by reducing serotonin production. Telotristat ethyl was evaluated in TELESTAR, a Phase III study for patients who had carcinoid syndrome with at least 4 bowel movements (BMs) per day and who were receiving somatostatin analogue therapy. This interview substudy was conducted to provide insight into the patient experience in TELESTAR and to help understand whether reductions in BM frequency (the primary end point) and other symptoms were clinically meaningful.

Methods: Participating sites were asked to invite (before randomization) all eligible patients to telephone interviews scheduled at …

Nanoparticle Delivery Of Mir-34a Eradicates Long-Term-Cultured Breast Cancer Stem Cells Via Targeting C22orf28 Directly, Xiaoti Lin, Weiyu Chen, Fengqin Wei, Binhua P. Zhou, Mien-Chie Hung, Xiaoming Xie

Molecular and Cellular Biochemistry Faculty Publications

Rationale: Cancer stem cells (CSCs) have been implicated as the seeds of therapeutic resistance and metastasis, due to their unique abilities of self-renew, wide differentiation potentials and resistance to most conventional therapies. It is a proactive strategy for cancer therapy to eradicate CSCs. Methods: Tumor tissue-derived breast CSCs (BCSC), including XM322 and XM607, were isolated by fluorescence-activated cell sorting (FACS); while cell line-derived BCSC, including MDA-MB-231.SC and MCF-7.SC, were purified by magnetic-activated cell sorting (MACS). Analyses of microRNA and mRNA expression array profiles were performed in multiple breast cell lines. The mentioned nanoparticles were constructed following the standard molecular cloning …

Influence Of Β-Lactam Infusion Strategy On Acute Kidney Injury, Sarah E. Cotner, Wilbur Cliff Rutter, Donna R. Burgess, Katie L. Wallace, Craig A. Martin, David S. Burgess

Pharmacy Practice and Science Faculty Publications

Limited literature is available assessing nephrotoxicity with prolonged β-lactam infusions. This study compared the incidence of acute kidney injury (AKI) associated with a prolonged β-lactam infusion or an intermittent infusion. This was a retrospective, matched-cohort study at an academic medical center from July 2006 to September 2015. Adult patients who received piperacillin-tazobactam (TZP), cefepime (FEP), or meropenem (MEM) for at least 48 h were evaluated. Patients were excluded for preexisting renal dysfunction or pregnancy. The primary outcome was difference in incidence of AKI evaluated using the RIFLE (risk, injury, failure, loss, and end-stage) criteria. Patients in the intermittent group …

Ketamine Use For Successful Resolution Of Post-Ercp Acute Pancreatitis Abdominal Pain, S Agerwala, D Sundarapandiyan, Garret Weber

NYMC Faculty Publications

We report a case in which a patient with intractable pain secondary to post-endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis is successfully treated with a subanesthetic ketamine infusion. Shortly after ERCP, the patient reported severe stabbing epigastric pain. She exhibited voluntary guarding and tenderness without distension. Amylase and lipase levels were elevated. Pain persisted for hours despite hydromorphone PCA, hydromorphone boluses, fentanyl boluses, and postprocedure anxiolytics. Pain management was consulted and a ketamine infusion was trialed, leading to a dramatic reduction in pain. This case suggests that ketamine may be a promising option in treating intractable pain associated with ERCP acute …

An Objective Assessment Of The Variability In Number Of Drops Per Bottle Of Glaucoma Medication, Daniel B. Moore, Judy Beck, Richard J. Kryscio

Ophthalmology and Visual Science Faculty Publications

Background: The purpose of this study is to evaluate the number of eyedrops available per bottle of a variety of commonly prescribed glaucoma medications.

Methods: Six bottles of each glaucoma medication were tested: three each in the vertical and horizontal orientations. Bottles were housed in a customized force gauge apparatus designed to mimic ballpoint fingertip contact with a bottle. At a standard rate, all drops were expressed from each bottle and counted with an automated drop counter. Simultaneously, bottle volume was measured and drop size and number were also estimated. The main outcome measures were: total number of drops, volume …

Pilot Study Comparing The Childhood Arthritis & Rheumatology Research Alliance (Carra) Systemic Juvenile Idiopathic Arthritis Consensus Treatment Plans., Yukiko Kimura, Sriharsha Grevich, Timothy Beukelman, Esi Morgan, Peter A. Nigrovic, Kelly Mieszkalski, T Brent Graham, Maria Ibarra, Norman Ilowite, Marisa Klein-Gitelman, Karen Onel, Sampath Prahalad, Marilynn Punaro, Sarah Ringold, Dana Toib, Heather Van Mater, Jennifer E. Weiss, Pamela F. Weiss, Laura E. Schanberg, Carra Registry Investigators

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To assess the feasibility of studying the comparative effectiveness of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plans (CTPs) for systemic Juvenile Idiopathic Arthritis (JIA) using an observational registry.

METHODS: Untreated systemic JIA patients enrolled in the CARRA Registry were begun on one of 4 CTPs chosen by the treating physician and patient/family (glucocorticoid [GC] alone; methotrexate [MTX] ± GC; IL1 inhibitor [IL1i] ± GC; IL6 inhibitor [IL6i] ± GC). The primary outcome of clinical inactive disease (CID) without current GC use was assessed at 9 months.

TRIAL REGISTRATION: clinicaltrials.gov NCT01697254; first registered 9/28/12 (retrospectively enrolled). …

Family Strategies To Support Siblings Of Pediatric Hematopoietic Stem Cell Transplant Patients., Taylor E. White, Kristopher A. Hendershot, Margie D. Dixon, Wendy Pelletier, Ann Haight, Kristin Stegenga, Melissa A. Alderfer, Lydia Cox, Jeffrey M. Switchenko, Pamela Hinds, Rebecca D. Pentz

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To describe the strategies families report using to address the needs and concerns of siblings of children, adolescents, and young adults undergoing hematopoietic stem cell transplant (HSCT).

METHODS: A secondary semantic analysis was conducted of 86 qualitative interviews with family members of children, adolescents, and young adults undergoing HSCT at 4 HSCT centers and supplemented with a primary analysis of 38 additional targeted qualitative interviews (23 family members, 15 health care professionals) conducted at the primary center. Analyses focused on sibling issues and the strategies families use to address these issues.

RESULTS: The sibling issues identified included: (1) feeling …

Multiple Targets For Novel Therapy Of Fsgs Associated With Circulating Permeability Factor., Virginia J. Savin, Mukut Sharma, Jianping Zhou, David Genochi, Ram Sharma, Tarak Srivastava, Amna Ilahe, Pooja Budhiraja, Aditi Gupta, Ellen T. Mccarthy

Manuscripts, Articles, Book Chapters and Other Papers

A plasma component is responsible for altered glomerular permeability in patients with focal segmental glomerulosclerosis. Evidence includes recurrence after renal transplantation, remission after plasmapheresis, proteinuria in infants of affected mothers, transfer of proteinuria to experimental animals, and impaired glomerular permeability after exposure to patient plasma. Therapy may include decreasing synthesis of the injurious agent, removing or blocking its interaction with cells, or blocking signaling or enhancing cell defenses to restore the permeability barrier and prevent progression. Agents that may prevent the synthesis of the permeability factor include cytotoxic agents or aggressive chemotherapy. Extracorporeal therapies include plasmapheresis, immunoadsorption with protein A …

Extracorporeal Membrane Oxygenation (Ecmo) For Severe Toxicological Exposures: Review Of The Toxicology Investigators Consortium (Toxic)., G S. Wang, R Levitan, T J. Wiegand, Jennifer Lowry, R F. Schult, S Yin, Toxicology Investigators Consortium

Manuscripts, Articles, Book Chapters and Other Papers

Although there have been many developments related to specific strategies for treating patients after poisoning exposures, the mainstay of therapy remains symptomatic and supportive care. One of the most aggressive supportive modalities is extracorporeal membrane oxygenation (ECMO). Our goal was to describe the use of ECMO for toxicological exposures reported to the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC). We performed a retrospective review of the ACMT ToxIC Registry from January 1, 2010 to December 31, 2013. Inclusion criteria included patients aged 0 to 89 years, evaluated between January 2010 through December 2013, and received ECMO for …

Use Of Medications Of Questionable Benefit In Advanced Dementia, Jennifer Tjia, Becky Briesacher, Daniel Peterson, Qin Liu, Susan Andrade, Susan Mitchell

Jennifer Tjia

IMPORTANCE: Advanced dementia is characterized by severe cognitive impairment and complete functional dependence. Patients' goals of care should guide the prescribing of medication during such terminal illness. Medications that do not promote the primary goal of care should be minimized. OBJECTIVES: To estimate the prevalence of medications with questionable benefit used by nursing home residents with advanced dementia, identify resident- and facility-level characteristics associated with such use, and estimate associated medication expenditures. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of medication use by nursing home residents with advanced dementia using a nationwide long-term care pharmacy database linked to the Minimum Data …

Mechanisms Of Bone Loss In Inflammatory Arthritis: Diagnosis And Therapeutic Implications, Steven R. Goldring, Ellen M. Gravallese

Ellen M. Gravallese

Rheumatoid arthritis represents an excellent model in which to gain insights into the local and systemic effects of joint inflammation on skeletal tissues. Three forms of bone disease have been described in rheumatoid arthritis. These include: focal bone loss affecting the immediate subchondral bone and bone at the joint margins; periarticular osteopenia adjacent to inflamed joints; and generalized osteoporosis involving the axial and appendicular skeleton. Although these three forms of bone loss have several features in common, careful histomorphometric and histopathological analysis of bone tissues from different skeletal sites, as well as the use of urinary and serum biochemical markers …

Interview With Celia Schiffer, Celia Schiffer

Celia A. Schiffer

Celia Schiffer, a Professor in Biochemistry and Molecular Pharmacology; a former Director of UMass Center for AIDS Research; and a Founder and Co-Director for the Institute for Drug Resistance (University of Massachusetts Medical School, MA, USA). Schiffer has an undergraduate degree in physics from the University of Chicago, with a PhD in biophysics from University of California, San Francisco (CA, USA). She was a postdoctoral associate first at the ETH in Zurich and then at Genentech in San Francisco. Schiffer has published more than 100 peer reviewed journal articles. Her laboratory primarily uses structural biology, biophysical and chemistry techniques to …

Antipsychotic Use In Nursing Homes Varies By Psychiatric Consultant, Jennifer Tjia, Terry Field, Celeste Lemay, Kathleen Mazor, Michelle Pandolfi, Ann Spenard, Shih-Yieh Ho, Abir Kanaan, Jennifer Donovan, Jerry Gurwitz, Becky Briesacher

Jennifer Tjia

BACKGROUND: The relationship between psychiatric consultation and antipsychotic prescribing in nursing homes (NH) is unknown. OBJECTIVE: To identify the association between psychiatric consultant groups and NH-level antipsychotic prescribing after adjustment for resident case-mix and facility characteristics. RESEARCH DESIGN AND SUBJECTS: Nested cross-sectional study of 60 NHs in a cluster randomized trial. We linked facility leadership surveys to October 2009-September 2010 Minimum Data Set, Nursing Home Compare, the US Census, and pharmacy dispensing data. MEASURES: The main exposure is the psychiatric consultant group and the main outcome is NH-level prevalence of atypical antipsychotic use. We calculated annual means and interquartile ranges …

Comparison Of Insulin Infusion Protocols Targeting 110-140 Mg/Dl In Patients After Cardiac Surgery., Vasudev Magaji, Shriddha Nayak, Amy Donihi, Lauren Willard, Srinivasa Jampana, Parachur Nivedita, Raymond Eder, Jann Johnston, Mary Korytkowski

Vasudev G Magaji MD, MS

BACKGROUND: Continuous intravenous insulin infusion (CII) following coronary artery bypass graft (CABG) surgery reduces postoperative complications and hospitalization duration. Because of limited data evaluating outcomes of CII with revised glycemic targets (110-140 mg/dL) in cardiac surgery, this study compared efficacy and safety of two different CII protocols having revised targets. SUBJECTS AND METHODS: This is a retrospective study comparing two different protocols between August 2009 and March 2010. Protocol 1 consists of four algorithms, and Protocol 2 is a table to adjust CII. Blood glucose (BG) and CII rates were recorded for 48 h postoperatively or CII discontinuation. Efficacy was …

Human Treg Responses Allow Sustained Recombinant Adeno-Associated Virus-Mediated Transgene Expression, Christian Mueller, Jeffrey Chulay, Bruce Trapnell, Margaret Humphries, Brenna Carey, Robert Sandhaus, Noel Mcelvaney, Louis Messina, Qiushi Tang, Farshid Rouhani, Martha Campbell-Thompson, Ann Fu, Anthony Yachnis, David Knop, Guo-Jie Ye, Mark Brantly, Roberto Calcedo, Suryanarayan Somanathan, Lee Richman, Robert Vonderheide, Maigan Hulme, Todd Brusko, James Wilson, Terence Flotte

Christian Mueller

Recombinant adeno-associated virus (rAAV) vectors have shown promise for the treatment of several diseases; however, immune-mediated elimination of transduced cells has been suggested to limit and account for a loss of efficacy. To determine whether rAAV vector expression can persist long term, we administered rAAV vectors expressing normal, M-type alpha-1 antitrypsin (M-AAT) to AAT-deficient subjects at various doses by multiple i.m. injections. M-specific AAT expression was observed in all subjects in a dose-dependent manner and was sustained for more than 1 year in the absence of immune suppression. Muscle biopsies at 1 year had sustained AAT expression and a reduction …

Wnt Pathway Reprogramming During Human Embryonal Carcinoma Differentiation And Potential For Therapeutic Targeting, Grace E. Snow, Allison C. Kasper, Alexander M. Busch, Elisabeth Schwarz, Katherine E. Ewings, Thomas Bee, Michael J. Spinella, Ethan Dmitrovsky, Sarah J. Freemantle

Dartmouth Scholarship

Testicular germ cell tumors (TGCTs) are classified as seminonas or non-seminomas of which a major subset is embryonal carcinoma (EC) that can differentiate into diverse tissues. The pluripotent nature of human ECs resembles that of embryonic stem (ES) cells. Many Wnt signalling species are regulated during differentiation of TGCT-derived EC cells. This study comprehensively investigated expression profiles of Wnt signalling components regulated during induced differentiation of EC cells and explored the role of key components in maintaining pluripotency.