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Synthesis And In-Vitro Cell Viability/Cytotoxicity Studies Of Novel Pyrrolobenzodiazepine Derivatives, John M. Jarrett 2017 East Tennessee State University

Synthesis And In-Vitro Cell Viability/Cytotoxicity Studies Of Novel Pyrrolobenzodiazepine Derivatives, John M. Jarrett

Undergraduate Honors Theses

Pyrrolobenzodiazepines (PBDs) are a group of naturally occurring compounds that were discovered in the cultures of Streptomyces in the 1960s. Some natural PBDs discovered in these cultures, such as anthramycin and sibiromycin, were shown to possess a broad spectrum of anti-tumor activity. Since cancer is still a leading cause of death globally, the development of novel anti-proliferative derivatives of PBDs is essential for human welfare worldwide. Further synthesis and structure-activity relationship (SAR) studies of the parent natural products and their tetracyclic analogs will lead to the discovery of drug candidates. In this work, thirteen PBD analogues were synthesized using no ...


Marijuana Regulation And Federalism, John M. Greabe 2017 University of New Hampshire School of Law

Marijuana Regulation And Federalism, John M. Greabe

Legal Scholarship

[Excerpt] "Federal law makes the cultivation and use of marijuana illegal for all purposes. Yet, over the past two decades, 28 states plus the District of Columbia have legalized marijuana for medicinal purposes, and eight states plus the District of Columbia have legalized it for recreational purposes. Marijuana regulation thus provides a useful and timely example for exploring the ways in which the distribution of power between the federal government and the states can facilitate policy change."


P03. Role Of Prefrontal Cortical Dopamine Transmission In Post-Traumatic Stress Disorder And Opiate Addiction Vulnerability, Jingjing Li 2017 Western University

P03. Role Of Prefrontal Cortical Dopamine Transmission In Post-Traumatic Stress Disorder And Opiate Addiction Vulnerability, Jingjing Li

Western Research Forum

Background

PTSD and opiate addiction share strong co-morbidity and the inability to suppress obtrusive memory recall related to either stressful or rewarding experiences may be an underlying neuropsychological feature triggering PTSD and/or addiction. Our previous research has shown that dopamine (DA) transmission in the prefrontal cortex (PFC) strongly modulates emotional memory formation: activation of the DA D4 receptor (D4R) strongly potentiates the emotional salience of normally non-salient fear memories whereas DA D1 receptor (D1R) activation blocks the behavioural recall of fear memory. Thus, while intra-PFC D4 transmission strongly controls the acquisition of emotional memory, D1 transmission is selectively involved ...


Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia, Brandon J. Baer 2017 University of Western Ontario

Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia, Brandon J. Baer

Western Research Forum

Background: Bacterial pneumonia is a leading cause of death worldwide, with high mortality rates persisting even after antibiotic treatment. Current treatments for pneumonia involve administration of antibiotics, however after the bacteria are killed they release toxic substances that induce inflammation and lung dysfunction. Host defense peptides represent a potential solution to this problem through their ability to down regulate inflammation. However, effective delivery to the lung is difficult because of the complex branching structure of the airways. My study addresses this delivery problem by using exogenous surfactant, a pulmonary delivery vehicle capable of improving spreading of these peptides throughout the ...


Session D-2: Don’T Overdose The Patient: A Unit Conversion Literacy Project, Gary M. Baker, David Anim-Addo, Patrick Young 2017 Northern Illinois University

Session D-2: Don’T Overdose The Patient: A Unit Conversion Literacy Project, Gary M. Baker, David Anim-Addo, Patrick Young

Professional Learning Day

General chemistry for non-science majors is often a prerequisite course for students pursuing degree programs in allied health fields, such as nursing. A core nursing skill is medicine management, which includes correctly calculating drug dosage volumes administered by I.V. or injection. Such calculations are nothing more than general chemistry problems involving concentration units and dilution. Our data show, however, that more than 90% of students lack this skill after taking a traditional general chemistry course. This presentation will focus on documenting this curricular gap and how we, as teachers, can address it.


Docking Studies Of Isoform-Selectivity Of Phosphatidylinositol 3-Kinase (Pi3k) Inhibitors, Kaitlin Goettsch 2017 University of Nebraska at Omaha

Docking Studies Of Isoform-Selectivity Of Phosphatidylinositol 3-Kinase (Pi3k) Inhibitors, Kaitlin Goettsch

Student Research and Creative Activity Fair

Phosphatidylinositol 3-kinases (PI3Ks) and their related pathways are reputed targets for drug-based anticancer therapies. Mutations in PI3K genes, expression, and pathways are frequent among multiple cancer types. Four isoforms of PI3Ks exist: α, β, γ, & δ and studies have identified several ligands for each isoform which are capable of serving as inhibitory therapeutic compounds. However, the biochemical efficacy of these molecules varies and the isoform selectivity is not well understood. In this study, we applied in silico docking methods and free energy calculation methods to estimate the binding of reported PI3K ligands against 5 PI3K structures: PI3Kα (PBD ID: 2RD0 ...


Effect Of Immediate Initiation Of Antiretroviral Therapy On Risk Of Severe Bacterial Infections In Hiv-Positive People With Cd4 Cell Counts Of More Than 500 Cells Per Μl: Secondary Outcome Results From A Randomised Controlled Trial., Jemma O'Connor, Michael J Vjecha, Andrew N Phillips, Brian Angus, David Cooper, Fred Gordin, +several additional authors 2017 George Washington University

Effect Of Immediate Initiation Of Antiretroviral Therapy On Risk Of Severe Bacterial Infections In Hiv-Positive People With Cd4 Cell Counts Of More Than 500 Cells Per Μl: Secondary Outcome Results From A Randomised Controlled Trial., Jemma O'Connor, Michael J Vjecha, Andrew N Phillips, Brian Angus, David Cooper, Fred Gordin, +Several Additional Authors

Medicine Faculty Publications

BACKGROUND: The effects of antiretroviral therapy on risk of severe bacterial infections in people with high CD4 cell counts have not been well described. In this study, we aimed to quantify the effects of immediate versus deferred ART on the risk of severe bacterial infection in people with high CD4 cell counts in a preplanned analysis of the START trial.

METHODS: The START trial was a randomised controlled trial in ART-naive HIV-positive patients with CD4 cell count of more than 500 cells per μL assigned to immediate ART or deferral until their CD4 cell counts were lower than 350 cells ...


Benzene Formation In Electronic Cigarettes, James F. Pankow, Kilsun Kim, Kevin J. McWhirter, Wentai Luo, Jorge O. Escobedo, Robert M. Strongin, Anna K. Duell, David H. Peyton 2017 Portland State University

Benzene Formation In Electronic Cigarettes, James F. Pankow, Kilsun Kim, Kevin J. Mcwhirter, Wentai Luo, Jorge O. Escobedo, Robert M. Strongin, Anna K. Duell, David H. Peyton

Chemistry Faculty Publications and Presentations

The heating of the fluids used in electronic cigarettes (“e-cigarettes”) used to create “vaping” aerosols is capable of causing a wide range of degradation reaction products. We investigated formation of benzene (an important human carcinogen) from e-cigarette fluids containing propylene glycol (PG), glycerol (GL), benzoic acid, the flavor chemical benzaldehyde, and nicotine.


Metastatic Biomarkers In Synovial Sarcoma, Rosalia de Necochea-Campion, Lee M. Zuckerman, Hamid R. Mirshahidi, Shahrzad Khosrowpour, Chien-Shing Chen, Saied Mirshahidi 2017 Loma Linda University

Metastatic Biomarkers In Synovial Sarcoma, Rosalia De Necochea-Campion, Lee M. Zuckerman, Hamid R. Mirshahidi, Shahrzad Khosrowpour, Chien-Shing Chen, Saied Mirshahidi

Library Articles and Research

Synovial sarcoma (SS) is an aggressive soft tissue sarcoma (STS) that typically occurs in the extremities near a joint. Metastatic disease is common and usually occurs in the lungs and lymph nodes. Surgical management is the mainstay of treatment with chemotherapy and radiation typically used as adjuvant treatment. Although chemotherapy has a positive impact on survival, the prognosis is poor if metastatic disease occurs. The biology of sarcoma invasion and metastasis remain poorly understood. Chromosomal translocation with fusion of the SYT and SSX genes has been described and is currently used as a diagnostic marker, although the full impact of ...


Cocoa Procyanidin And Β-Cell Proliferation, Whitney Harris, Alonzo Cook PhD, Michael Scott Brashaw III, Jeffrey Brown, Kyril Cole, Kody Hasebi, Ysabella Del Rosario, Sara Werner, Bryan Samuel Witt 2017 Brigham Young University

Cocoa Procyanidin And Β-Cell Proliferation, Whitney Harris, Alonzo Cook Phd, Michael Scott Brashaw Iii, Jeffrey Brown, Kyril Cole, Kody Hasebi, Ysabella Del Rosario, Sara Werner, Bryan Samuel Witt

Biomedical Engineering Western Regional Conference

This presentation explains an experiment that attempts to provide a more thorough understanding on the effect of cocoa procyanidin on β-Cell proliferation in diabetic rats in order to advance the treatment of diabetes.


Longitudinal Changes In Neurodevelopmental Outcomes Between 18 And 36 Months In Children With Prenatal Triptan Exposure: Findings From The Norwegian Mother And Child Cohort Study, Mollie E. Wood, Jean A. Frazier, Hedvig M.E. Nordeng, Kate L. Lapane 2017 University of Massachusetts Medical School

Longitudinal Changes In Neurodevelopmental Outcomes Between 18 And 36 Months In Children With Prenatal Triptan Exposure: Findings From The Norwegian Mother And Child Cohort Study, Mollie E. Wood, Jean A. Frazier, Hedvig M.E. Nordeng, Kate L. Lapane

Jean A. Frazier

OBJECTIVE: This study sought to determine whether changes in neurodevelopmental outcomes between 18 and 36 months of age were associated with prenatal exposure to triptan medications, a class of 5-HT receptor agonists used in the treatment of migraine. METHOD: Using data from the Norwegian Mother and Child Cohort Study, a prospective birth cohort that includes nearly 40% of all pregnancies in Norway from 1999 to 2008, we identified 50 469 mother-child dyads who met inclusion criteria and were present for at least one follow-up assessment at 18 or 36 months postpartum. Neurodevelopment was assessed using the Child Behaviour Checklist, the ...


Mitochondria Mediate Cell Membrane Repair And Contribute To Duchenne Muscular Dystrophy., Maria C Vila, Sree Rayavarapu, Marshall W Hogarth, Jack H Van der Meulen, Adam Horn, Aurelia Defour, Shin'ichi Takeda, Kristy J. Brown, Yetrib Hathout, Kanneboyina Nagaraju, Jyoti K. Jaiswal 2017 George Washington University

Mitochondria Mediate Cell Membrane Repair And Contribute To Duchenne Muscular Dystrophy., Maria C Vila, Sree Rayavarapu, Marshall W Hogarth, Jack H Van Der Meulen, Adam Horn, Aurelia Defour, Shin'ichi Takeda, Kristy J. Brown, Yetrib Hathout, Kanneboyina Nagaraju, Jyoti K. Jaiswal

Integrative Systems Biology Faculty Publications

Dystrophin deficiency is the genetic basis for Duchenne muscular dystrophy (DMD), but the cellular basis of progressive myofiber death in DMD is not fully understood. Using two dystrophin-deficient mdx mouse models, we find that the mitochondrial dysfunction is among the earliest cellular deficits of mdx muscles. Mitochondria in dystrophic myofibers also respond poorly to sarcolemmal injury. These mitochondrial deficits reduce the ability of dystrophic muscle cell membranes to repair and are associated with a compensatory increase in dysferlin-mediated membrane repair proteins. Dysferlin deficit in mdx mice further compromises myofiber cell membrane repair and enhances the muscle pathology at an asymptomatic ...


A Case For Caution: An Evaluation Of Calabrese And Baldwin's Studies Of Chemical Hormesis, Kevin C. Elliott 2017 University of New Hampshire

A Case For Caution: An Evaluation Of Calabrese And Baldwin's Studies Of Chemical Hormesis, Kevin C. Elliott

RISK: Health, Safety & Environment

Suggesting a need for more research, Mr. Elliott argues that it is too soon for risk-assessment policy to account for recent challenges to a toxicological linear dose-response assumption.


Comparing The Epa Indoor Air Quality Personal Computer Model And Field Data, Arash Behravesh, Wilbur A. Spaul 2017 University of New Hampshire

Comparing The Epa Indoor Air Quality Personal Computer Model And Field Data, Arash Behravesh, Wilbur A. Spaul

RISK: Health, Safety & Environment

The authors recommend caution in using an EPA model for reconstructing past exposure events as well as for predicting future exposures.


Tricresyl Phosphate Neurotoxicity Potential, George William Sherk 2017 University of New Hampshire

Tricresyl Phosphate Neurotoxicity Potential, George William Sherk

RISK: Health, Safety & Environment

Mr. Sherk discusses the potential effects of ongoing human exposure to ordinary doses of neurotoxicants.


Computational Analysis Of Residue Interaction Networks And Coevolutionary Relationships In The Hsp70 Chaperones: A Community- Hopping Model Of Allosteric Regulation And Communication, Gabrielle Stetz, Gennady M. Verkhivker 2017 Chapman University

Computational Analysis Of Residue Interaction Networks And Coevolutionary Relationships In The Hsp70 Chaperones: A Community- Hopping Model Of Allosteric Regulation And Communication, Gabrielle Stetz, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Allosteric interactions in the Hsp70 proteins are linked with their regulatory mechanisms and cellular functions. Despite significant progress in structural and functional characterization of the Hsp70 proteins fundamental questions concerning modularity of the allosteric interaction networks and hierarchy of signaling pathways in the Hsp70 chaperones remained largely unexplored and poorly understood. In this work, we proposed an integrated computational strategy that combined atomistic and coarse-grained simulations with coevolutionary analysis and network modeling of the residue interactions. A novel aspect of this work is the incorporation of dynamic residue correlations and coevolutionary residue dependencies in the construction of allosteric interaction networks ...


Maysin And Its Flavonoid Derivative From Centipedegrass Attenuates Amyloid Plaques By Inducting Humoral Immune Response With Th2 Skewed Cytokine Response In The Tg (Appswe, Ps1de9) Alzheimer's Mouse Model, Yuno Song, Hong-Duck Kim, Min-Kwon Lee, Il-Hwa Hong, Chung-Kil Won, Seung Sik Lee, Jae-Hyeon Cho 2017 New York Medical College

Maysin And Its Flavonoid Derivative From Centipedegrass Attenuates Amyloid Plaques By Inducting Humoral Immune Response With Th2 Skewed Cytokine Response In The Tg (Appswe, Ps1de9) Alzheimer's Mouse Model, Yuno Song, Hong-Duck Kim, Min-Kwon Lee, Il-Hwa Hong, Chung-Kil Won, Seung Sik Lee, Jae-Hyeon Cho

NYMC Faculty Publications

Alzheimer's disease (AD) is a slow, progressive neurodegenerative disease and the most common type of dementia in the elderly. The etiology of AD and its underlying mechanism are still not clear. In a previous study, we found that an ethyl acetate extract of Centipedegrass (CG) (i.e., EA-CG) contained 4 types of Maysin derivatives, including Luteolin, Isoorientin, Rhamnosylisoorientin, and Derhamnosylmaysin, and showed protective effects against Amyloid beta (Aβ) by inhibiting oligomeric Aβ in cellular and in vitro models. Here, we examined the preventative effects of EA-CG treatment on the Aβ burden in the Tg (Mo/Hu APPswe PS1dE9) AD ...


Assessment Of The Use Of Overdose Education And Naloxone Distribution By Maine Buprenorphine/Naloxone Prescribers, Stephen Kirsch 2017 University of Southern Maine

Assessment Of The Use Of Overdose Education And Naloxone Distribution By Maine Buprenorphine/Naloxone Prescribers, Stephen Kirsch

Muskie School Capstones

Background: Overdose deaths, specifically related to opioids, have been identified as a public health problem both nationally and in the state of Maine. Overdose Education and Naloxone Distribution (OEND) is an innovative model of patient education that has been shown to be effective in increasing knowledge of overdose risk and has the potential to help reduce opiate related overdose deaths.

Methods: A 28-item web-based survey examining clinician attitudes, OEND practices and characteristics was distributed to 196 Maine based physicians with a Drug Enforcement Agency waiver to prescribe burprenorphine/naloxone. Facilitators and barriers to the provision of OEND were also assessed ...


Cyclic Ac253, A Novel Amylin Receptor Antagonist, Improves Cognitive Deficits In A Mouse Model Of Alzheimer’S Disease, Rania Soudy, Aarti Patel, Wen Fu, Kamaljit Kaur, David MacTavish, David Westaway, Rachel Davey, Jeffrey Zajac, Jack Jhamandas 2017 University of Alberta

Cyclic Ac253, A Novel Amylin Receptor Antagonist, Improves Cognitive Deficits In A Mouse Model Of Alzheimer’S Disease, Rania Soudy, Aarti Patel, Wen Fu, Kamaljit Kaur, David Mactavish, David Westaway, Rachel Davey, Jeffrey Zajac, Jack Jhamandas

Pharmacy Faculty Articles and Research

Introduction: Amylin receptor serves as a portal for the expression of deleterious effects of amyloid b-protein (Ab), a key pathologic hallmark of Alzheimer’s disease. Previously, we showed that AC253, an amylin receptor antagonist, is neuroprotective against Ab toxicity in vitro and abrogates Ab-induced impairment of hippocampal long-term potentiation.

Methods: Amyloid precursor protein–overexpressing TgCRND8 mice received intracerebroventricularly AC253 for 5 months. New cyclized peptide cAC253 was synthesized and administered intraperitoneally three times a week for 10 weeks in the same mouse model. Cognitive functions were monitored, and pathologic changes were quantified biochemically and immunohistochemically.

Results: AC253, when administered intracerebroventricularly ...


Unmasking Of Myoclonus By Lacosamide In Generalized Epilepsy, Daniel Birnbaum, Mohamad Z. Koubeissi 2017 George Washington University

Unmasking Of Myoclonus By Lacosamide In Generalized Epilepsy, Daniel Birnbaum, Mohamad Z. Koubeissi

Neurology Faculty Publications

Lacosamide is a new-generation antiseizure medication that is approved for use as an adjunctive treatment and monotherapy in focal epilepsy. Its use in generalized epilepsy, however, has not been adequately evaluated in controlled trials. We report a 67-year-old woman who experienced new-onset myoclonic seizures after initiation of lacosamide. We presume that she had an undiagnosed generalized epilepsy syndrome, likely juvenile myoclonic epilepsy. Myoclonic seizures were not reported before introducing lacosamide and completely resolved after lacosamide was discontinued. This suggests that lacosamide may have the potential to worsen myoclonus, similar to what has been reported with another sodium channel agent, lamotrigine ...


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