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Refrigerated Stability Of Diluted Cisatracurium, Rocuronium, And Vecuronium For Skin Testing After Perioperative Anaphylaxis, Kristen Dinsmore, Bethany Campbell, Timothy Archibald, Greg Mosier, Stacy Brown PhD, Alexei Gonzalez-Estrada MD 2018 East Tennessee State University

Refrigerated Stability Of Diluted Cisatracurium, Rocuronium, And Vecuronium For Skin Testing After Perioperative Anaphylaxis, Kristen Dinsmore, Bethany Campbell, Timothy Archibald, Greg Mosier, Stacy Brown Phd, Alexei Gonzalez-Estrada Md

Appalachian Student Research Forum

Rationale: The purpose of this study is to investigate the stored stability of dilutions of neuromuscular blocking agents (NMBAs), namely cisatracurium, rocuronium, and vecuronium, for skin prick/intradermal testing.

Methods: Concentrations of NMBAs were monitored by liquid chromatography-mass spectrometry (LC-MS/MS) for a period of 14 days. Dilutions of NMBAs were prepared in saline by factors of 10x, 100x, 1,000x, 10,000x, and 100,000x as sensitivity of the assay allowed. Diluted drug products were stored in a laboratory refrigerator until sampling. On sampling days, aliquots of each dilution were removed and compared to a freshly prepared set of ...


Sirna Knock-Down Of Vav1 In Breast Cancer Cells: Effects On Pi3kinase And Akt, Tajai Sion-Milligan 2018 Lynchburg College

Sirna Knock-Down Of Vav1 In Breast Cancer Cells: Effects On Pi3kinase And Akt, Tajai Sion-Milligan

Student Scholar Showcase

One in eight women in the United States will be diagnosed with breast cancer. Approximately 25-30% of these breast tumors will overexpress Human Epidermal Growth Factor Receptor 2 (HER2), associated with a worse prognosis and decreased survival rate. Stimulation of HER2 results in activation and production of many signaling molecules, ultimately resulting in increased cell division. Two of the downstream molecules activated are PI3Kinase and, further downstream, the molecule Akt. Typically, overproduction and/or overactivation of PI3Kinase can lead to oncogenesis. A molecule that may have a significant role in PI3Kinase formation is VAV1 ...


Antibiotic Residues In Milk From Three Popular Kenyan Milk Vending Machines, Amos Kosgey, Anakalo Shitandi, Jason W. Marion 2018 Eastern Kentucky University

Antibiotic Residues In Milk From Three Popular Kenyan Milk Vending Machines, Amos Kosgey, Anakalo Shitandi, Jason W. Marion

EKU Faculty and Staff Scholarship

Milk vending machines (MVMs) are growing in popularity in Kenya and worldwide. Milk vending machines dispense varying quantities of locally sourced, pasteurized milk. The Kenya Dairy Board has a regulatory framework, but surveillance is weak because of several factors. Milk vending machines’ milk is not routinely screened for antibiotics, thereby increasing potential for antibiotic misuse. To investigate, a total of 80 milk samples from four commercial providers (N = 25), street vendors (N = 21), and three MVMs (N = 34) were collected and screened in Eldoret, Kenya. Antibiotic residue surveillance occurred during December 2016 and January 2017 using Idexx SNAP tests for ...


Acute Hepatic Failure And Oral Amiodarone, Hani Alhamoud, Sivateja Mandava, Talal Alzahrani 2018 George Washington University

Acute Hepatic Failure And Oral Amiodarone, Hani Alhamoud, Sivateja Mandava, Talal Alzahrani

GW Research Days 2016 - Present

Introduction:

Amiodarone is associated with serious complications such as lung toxicity, thyroid dysfunction, and QT-prolongation. Further, hepatic failure from the intravenous (IV) formulation of amiodarone is described in numerous case reports and case series. Although there are reports of elevated liver enzymes from the oral formulation of amiodarone, to our knowledge, none have definitively identified a case of acute hepatic failure from the oral formulation alone. In this case, we report an instance of acute hepatic failure after increasing the oral amiodarone dosage as well as rapid recovery following cessation of the medication.

Case report:

A 61-year-old male with a ...


Onyx Use In Extracranial Pathologies - A Retrospective Case Review, Faezeh Razjouyan, Rishi Sood, Alex Cho, Anthony Venbrux, Shawn Sarin 2018 George Washington University

Onyx Use In Extracranial Pathologies - A Retrospective Case Review, Faezeh Razjouyan, Rishi Sood, Alex Cho, Anthony Venbrux, Shawn Sarin

GW Research Days 2016 - Present

Purpose:

Onyx is an embolic agent currently FDA approved for neurointerventional procedures such as in the treatment of aneurysms and arteriovenous malformations. Despite its limited indications, the agent's off-label use in the treatment of extracranial pathologies continues to increase. To date, there has not been a single-center study demonstrating a large number of cases demonstrating safe and effective peripheral embolization with Onyx.

Materials:

We performed a retrospective review of all cases that used Onyx between October 2010 and July 2016 at a single tertiary care academic university urban hospital. Institutional review board approval was appropriately obtained. Initial case selection ...


Pupillometric Assessment Of Small Doses Of Opioid In A Pediatric Population, David Strum, Elizabeth Malphrus, Kevin Jackson, Julia Finkel 2018 George Washington University

Pupillometric Assessment Of Small Doses Of Opioid In A Pediatric Population, David Strum, Elizabeth Malphrus, Kevin Jackson, Julia Finkel

GW Research Days 2016 - Present

According to the CDC, opioid prescriptions in the United States have more than tripled from 1999-2014, which has correlated with the staggering increase in opioid-involved drug overdose deaths. This pattern of prescription is thought to be a major contributory factor to the increase in drug overdose in America, as four out of five new heroin users started by misusing prescription painkillers. Providers need the means to objectively monitor analgesic efficacy of treatment in patients with pain to mitigate unnecessary analgesic prescribing.

It is well established that mu opioid agonists like morphine cause miosis, an effect to which tolerance does not ...


Cannabis-Related Content In North American Post-Secondary Curricula: A Scoping Review, Tianhao Xiao 2018 Thompson Rivers University

Cannabis-Related Content In North American Post-Secondary Curricula: A Scoping Review, Tianhao Xiao

Proceedings of the Annual Thompson Rivers University Undergraduate Research and Innovation Conference

On 11 August 2016, the Canadian government announced the new Access to Cannabis for Medical Purposes Regulations (ACMPR) outlining reasonable uses of cannabis for medical purposes. Educators teaching cannabis-related content face new challenges, as this legalization requires a shift away from a focus on substance abuse towards incorporating economic, social, and health promotion aspects. I report on what curricula incorporating the concept of cannabis are offered by post-secondary institutions as well as how and for what purpose this content is offered. To do this, I conducted a scoping review of published and grey literature to determine the extent of the ...


Studies Of Amino Acid Mutations In Drug Resistance Of The Smo Protein, Eunice Wintona 2018 University of Nebraska at Omaha

Studies Of Amino Acid Mutations In Drug Resistance Of The Smo Protein, Eunice Wintona

Student Research and Creative Activity Fair

Smoothened receptor (SMO) is a protein that in humans, is encoded by the SMO gene. A systemic mutation in its binding pocket helps predict the sensitivity of mutant proteins to different drugs. Known as a GPCR-like receptor, it is a component of the hedgehog signaling pathway; a pathway involved in body patterning and the regulation of adult stem cells. An uncontrolled or inappropriate activation of the Hedgehog pathway drives tumor progression in cancers and a number of birth defects. To achieve these goals, the molecular modeling software MOE was used to build small molecules and drug molecules like Vismodegib and ...


Transcriptome Profiling Of Neovascularized Corneas Reveals Mir-204 As A Multi-Target Biotherapy Deliverable By Raavs, Yi Lu, Phillip W. L. Tai, Jianzhong Ai, Dominic J. Gessler, Qin Su, Xieyi Yao, Qiang Zheng, Phillip D. Zamore, Xun Xu, Guangping Gao 2018 University of Massachusetts Medical School

Transcriptome Profiling Of Neovascularized Corneas Reveals Mir-204 As A Multi-Target Biotherapy Deliverable By Raavs, Yi Lu, Phillip W. L. Tai, Jianzhong Ai, Dominic J. Gessler, Qin Su, Xieyi Yao, Qiang Zheng, Phillip D. Zamore, Xun Xu, Guangping Gao

Open Access Articles

Corneal neovascularization (NV) is the major sight-threatening pathology caused by angiogenic stimuli. Current drugs that directly target pro-angiogenic factors to inhibit or reverse the disease require multiple rounds of administration and have limited efficacies. Here, we identify potential anti-angiogenic corneal microRNAs (miRNAs) and demonstrate a framework that employs discovered miRNAs as biotherapies deliverable by recombinant adeno-associated viruses (rAAVs). By querying differentially expressed miRNAs in neovascularized mouse corneas induced by alkali burn, we have revealed 39 miRNAs that are predicted to target more than 5,500 differentially expressed corneal mRNAs. Among these, we selected miR-204 and assessed its efficacy and therapeutic ...


Cerebral Organoids Derived From Sandhoff Disease-Induced Pluripotent Stem Cells Exhibit Impaired Neurodifferentiation, Maria L. Allende, Emily K. Cook, Bridget C. Larman, Adrienne Nugent, Jacqueline M. Brady, Diane Golebiowski, Miguel Sena-Esteves, Cynthia J. Tifft, Richard L. Proia 2018 National Institutes of Health

Cerebral Organoids Derived From Sandhoff Disease-Induced Pluripotent Stem Cells Exhibit Impaired Neurodifferentiation, Maria L. Allende, Emily K. Cook, Bridget C. Larman, Adrienne Nugent, Jacqueline M. Brady, Diane Golebiowski, Miguel Sena-Esteves, Cynthia J. Tifft, Richard L. Proia

Open Access Articles

Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder characterized by the absence of beta-hexosaminidase A and B activity and the concomitant lysosomal accumulation of its substrate, GM2 ganglioside. It features catastrophic neurodegeneration and death in early childhood. How the lysosomal accumulation of ganglioside might affect the early development of the nervous system is not understood. Recently, cerebral organoids derived from induced pluripotent stem (iPS) cells have illuminated early developmental events altered by disease processes. To develop an early neurodevelopmental model of Sandhoff disease, we first generated iPS cells from the fibroblasts of an infantile Sandhoff disease ...


Impact Of A Pilot Outreach Program Upon Provider Awareness And Prescribing Of A Concerning Opioid Combination Regimen, Briana Santaniello, Thomas C. Pomfret, Mark A. Tesell, Nicole M. Trask, Caroline J. Alper, Karen M. Clements, Vincent Palumbo, Kimberly Lenz, Paul L. Jeffrey 2018 Magellan Rx Management

Impact Of A Pilot Outreach Program Upon Provider Awareness And Prescribing Of A Concerning Opioid Combination Regimen, Briana Santaniello, Thomas C. Pomfret, Mark A. Tesell, Nicole M. Trask, Caroline J. Alper, Karen M. Clements, Vincent Palumbo, Kimberly Lenz, Paul L. Jeffrey

Commonwealth Medicine Publications

This pilot program was developed in response to a drug utilization review within a large Medicaid population that revealed some hazardous practices. Co-prescribing of opioids with benzodiazepines, gabapentin, and other stimulants occurred in more than 500 members, putting them at risk for additive central nervous system depression, misuse, abuse, and death from overdose.

The poster presentation outlines the objectives, methods, and results of a telephonic outreach program that addressed these safety concerns. It captures prescriber awareness of the presence and risks of potentially deadly medication combinations among members in their care, with some intriguing results.

Our experts provide health plans ...


A Budget Impact Model For Two Investigational Agents For The Treatment Of Nonalcoholic Steatohepatitis, Nicole M. Trask, Pavel Lavitas, Vincent Palumbo 2018 University of Massachusetts Medical School

A Budget Impact Model For Two Investigational Agents For The Treatment Of Nonalcoholic Steatohepatitis, Nicole M. Trask, Pavel Lavitas, Vincent Palumbo

Commonwealth Medicine Publications

Statistics show approximately 15 million Americans suffer from NASH, a nonalcoholic fatty liver disease that is projected to become the most common reason for liver transplantation. There are no FDA approved therapies for NASH, so doctors are forced to treat patients with off-label medications while keeping an eye out for breakthroughs in medication development.

Two novel therapies, obeticholic acid and elafibranor, are currently in Phase III trials. If they receive FDA approval, interest will be high as they will be the first treatments specifically labeled for NASH. We detail a budget impact model for a sample state Medicaid plan in ...


The Biologics Price Competition And Innovation Act: Is A Generic Market For Biologics Attainable?, Kasey E. Koballa 2018 College of William & Mary Law School

The Biologics Price Competition And Innovation Act: Is A Generic Market For Biologics Attainable?, Kasey E. Koballa

William & Mary Business Law Review

The Biologics Price Competition and Innovation Act of 2009 (BPCIA) provides an abbreviated approval pathway for biological therapeutic products shown to be biosimilar to an FDA-approved biological reference product. The BPCIA purported to reduce the price of biologics while promoting innovation. In two recent cases, the Federal Circuit interpreted a key provision of the BPCIA requiring an applicant to provide the reference product sponsor with notice 180 days before marketing the product. The Federal Circuit’s interpretation extends the exclusivity period already provided for the reference product sponsor, deterring innovation and price reduction. Thus, the Supreme Court granted certiorari in ...


Comparison Of Partially And Fully Chemically-Modified Sirna In Conjugate-Mediated Delivery In Vivo, Matthew R. Hassler, Anton A. Turanov, Julia F. Alterman, Reka A. Haraszti, Andrew H. Coles, Maire F. Osborn, Dimas Echeverria, Mehran Nikan, William E. Salomon, Loic Roux, Bruno M. D. C. Godinho, Sarah M. Davis, David V. Morrissey, Phillip D. Zamore, S. Ananth Karumanchi, Melissa J. Moore, Neil Aronin, Anastasia Khvorova 2018 University of Massachusetts Medical School

Comparison Of Partially And Fully Chemically-Modified Sirna In Conjugate-Mediated Delivery In Vivo, Matthew R. Hassler, Anton A. Turanov, Julia F. Alterman, Reka A. Haraszti, Andrew H. Coles, Maire F. Osborn, Dimas Echeverria, Mehran Nikan, William E. Salomon, Loic Roux, Bruno M. D. C. Godinho, Sarah M. Davis, David V. Morrissey, Phillip D. Zamore, S. Ananth Karumanchi, Melissa J. Moore, Neil Aronin, Anastasia Khvorova

Open Access Articles

Small interfering RNA (siRNA)-based drugs require chemical modifications or formulation to promote stability, minimize innate immunity, and enable delivery to target tissues. Partially modified siRNAs (up to 70% of the nucleotides) provide significant stabilization in vitro and are commercially available; thus are commonly used to evaluate efficacy of bio-conjugates for in vivo delivery. In contrast, most clinically-advanced non-formulated compounds, using conjugation as a delivery strategy, are fully chemically modified (100% of nucleotides). Here, we compare partially and fully chemically modified siRNAs in conjugate mediated delivery. We show that fully modified siRNAs are retained at 100x greater levels in various ...


Cbx7 Regulates Stem Cell-Like Properties Of Gastric Cancer Cells Via P16 And Akt-Nf-Κb-Mir-21 Pathways., Su-Jie Ni, Li-Qin Zhao, Xiao-Feng Wang, Zhen-Hua Wu, Rui-Xi Hua, Chun-Hua Wan, Jie-Yun Zhang, Xiao-Wei Zhang, Ming-Zhu Huang, Lu Gan, Hua-Lin Sun, Goberdhan P Dimri, Wei-Jian Guo 2018 George Washington University

Cbx7 Regulates Stem Cell-Like Properties Of Gastric Cancer Cells Via P16 And Akt-Nf-Κb-Mir-21 Pathways., Su-Jie Ni, Li-Qin Zhao, Xiao-Feng Wang, Zhen-Hua Wu, Rui-Xi Hua, Chun-Hua Wan, Jie-Yun Zhang, Xiao-Wei Zhang, Ming-Zhu Huang, Lu Gan, Hua-Lin Sun, Goberdhan P Dimri, Wei-Jian Guo

Biochemistry and Molecular Medicine Faculty Publications

BACKGROUND: Chromobox protein homolog 7 (CBX7), a member of the polycomb group (PcG) family of proteins, is involved in the regulation of cell proliferation and cancer progression. PcG family members, such as BMI, Mel-18, and EZH2, are integral constituents of the polycomb repressive complexes (PRCs) and have been known to regulate cancer stem cell (CSC) phenotype. However, the role of other PRCs' constituents such as CBX7 in the regulation of CSC phenotype remains largely elusive. This study was to investigate the role of CBX7 in regulating stem cell-like properties of gastric cancer and the underlying mechanisms.

METHODS: Firstly, the role ...


Novel Combination Bmp7 And Hgf Gene Therapy Instigates Selective Myofibroblast Apoptosis And Reduces Corneal Haze In Vivo, Suneel Gupta, Michael K. Fink, Arkasubhra Ghosh, Ratnakar Tripathi, Prashant R. Sinha, Ajay Sharma, Nathan P. Hesemann, Shyam S. Chaurasia, Elizabeth A. Giuliano, Rajiv R. Mohan 2018 Harry S. Truman Memorial Veterans’ Hospital

Novel Combination Bmp7 And Hgf Gene Therapy Instigates Selective Myofibroblast Apoptosis And Reduces Corneal Haze In Vivo, Suneel Gupta, Michael K. Fink, Arkasubhra Ghosh, Ratnakar Tripathi, Prashant R. Sinha, Ajay Sharma, Nathan P. Hesemann, Shyam S. Chaurasia, Elizabeth A. Giuliano, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE. We tested the potential of bone morphogenic protein 7 (BMP7) and hepatocyte growth factor (HGF) combination gene therapy to treat preformed corneal fibrosis using established rabbit in vivo and human in vitro models.

METHODS. Eighteen New Zealand White rabbits were used. Corneal fibrosis was produced by alkali injury. Twenty-four hours after scar formation, cornea received topically either balanced salt solution (BSS; n ¼ 6), polyethylenimine-conjugated gold nanoparticle (PEI2-GNP)-naked plasmid (n ¼ 6) or PEI2-GNP plasmids expressing BMP7 and HGF genes (n ¼ 6). Donor human corneas were used to obtain primary human corneal fibroblasts and myofibroblasts for mechanistic ...


Simian Virus 40 Large T Antigen As A Model To Test The Efficacy Of Flouroquinolones Against Viral Helicases, Sammer Siddiqui, Muhammad F. Anwar, Sadaf Naeem, Syed Hani Abidi, Shamshad Zarina, Syed Ali 2018 Tulane University, New Orleans, LA, USA

Simian Virus 40 Large T Antigen As A Model To Test The Efficacy Of Flouroquinolones Against Viral Helicases, Sammer Siddiqui, Muhammad F. Anwar, Sadaf Naeem, Syed Hani Abidi, Shamshad Zarina, Syed Ali

Department of Biological & Biomedical Sciences

Simian virus 40 large T-antigen (SV40 LT-Ag) is a 708 amino acid nuclear phosphoprotein. Among many functions of LT-Ag is its ability to perform as an ATPase-helicase, catalyzing the unwinding of viral genome during replication. The LT-Ag has been employed in the studies of helicase structure and function, and has served as a model helicase for the screening of antiviral drugs that target viral helicase. In this study, using in vitro enzyme assays and in silico computer modeling, we screened a batch of 18 fluoroquinolones to assess their potential as antivirals by virtue of their inhibition of the LT-Ag helicase ...


Matrix Metalloproteinase-14 Is A Mechanically Regulated Activator Of Secreted Mmps And Invasion, Amanda Haage, Dong Hyun Nam, Xin Ge, Ian C. Schneider 2018 Iowa State University

Matrix Metalloproteinase-14 Is A Mechanically Regulated Activator Of Secreted Mmps And Invasion, Amanda Haage, Dong Hyun Nam, Xin Ge, Ian C. Schneider

Ian C. Schneider

Matrix metalloproteinases (MMPs) are extracellular matrix (ECM) degrading enzymes and have complex and specific regulation networks. This includes activation interactions, where one MMP family member activates another. ECM degradation and MMP activation can be initiated by several different stimuli including changes in ECM mechanical properties or intracellular contractility. These mechanical stimuli are known enhancers of metastatic potential. MMP-14 facilitates local ECM degradation and is well known as a major mediator of cell migration, angiogenesis and invasion. Recently, function blocking antibodies have been developed to specifically block MMP-14, providing a useful tool for research as well as therapeutic applications. Here we ...


Better Living Through Chemistry: Addressing Emerging Antibiotic Resistance, Nathan P. Coussens, Ashley L. Molinaro, Kayla J. Culbertson, Tyler Peryea, Gergely Zahoránszky-Köhalmi, Matthew D. Hall, Dayle A. Daines 2018 Old Dominion University

Better Living Through Chemistry: Addressing Emerging Antibiotic Resistance, Nathan P. Coussens, Ashley L. Molinaro, Kayla J. Culbertson, Tyler Peryea, Gergely Zahoránszky-Köhalmi, Matthew D. Hall, Dayle A. Daines

Biological Sciences Faculty Publications

The increasing emergence of multidrug-resistant bacteria is recognized as a major threat to human health worldwide. While the use of small molecule antibiotics has enabled many modern medical advances, it has also facilitated the development of resistant organisms. This minireview provides an overview of current small molecule drugs approved by the US Food and Drug Administration (FDA) for use in humans, the unintended consequences of antibiotic use, and the mechanisms that underlie the development of drug resistance. Promising new approaches and strategies to counter antibiotic-resistant bacteria with small molecules are highlighted. However, continued public investment in this area is critical ...


Effects Of Clinical Pathway Implementation On Antibiotic Prescriptions For Pediatric Community-Acquired Pneumonia., Daniele Donà, Silvia Zingarella, Andrea Gastaldi, Rebecca Lundin, Giorgio Perilongo, Anna Chiara Frigo, Rana F Hamdy, Theoklis Zaoutis, Liviana Da Dalt, Carlo Giaquinto 2018 George Washington University

Effects Of Clinical Pathway Implementation On Antibiotic Prescriptions For Pediatric Community-Acquired Pneumonia., Daniele Donà, Silvia Zingarella, Andrea Gastaldi, Rebecca Lundin, Giorgio Perilongo, Anna Chiara Frigo, Rana F Hamdy, Theoklis Zaoutis, Liviana Da Dalt, Carlo Giaquinto

Pediatrics Faculty Publications

BACKGROUND: Italian pediatric antimicrobial prescription rates are among the highest in Europe. As a first step in an Antimicrobial Stewardship Program, we implemented a Clinical Pathway (CP) for Community Acquired Pneumonia with the aim of decreasing overall prescription of antibiotics, especially broad-spectrum.

MATERIALS AND METHODS: The CP was implemented on 10/01/2015. We collected antibiotic prescribing and outcomes data from children aged 3 months-15 years diagnosed with CAP from 10/15/2014 to 04/15/2015 (pre-intervention period) and from 10/15/2015 to 04/15/2016 (post-intervention period). We assessed antibiotic prescription differences pre- and post-CP, including rates ...


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