Pharmacy and Pharmaceutical Sciences Commons^™

Three-Dimensional Imaging Of Kndy Neurons In The Mammalian Brain Using Optical Tissue Clearing And Multiple-Label Immunocytochemistry, Aleisha M. Moore, Kathryn A. Lucas, Robert L. Goodman, Lique M. Coolen, Michael N. Lehman

Faculty & Staff Scholarship

Kisspeptin/Neurokinin B/Dynorphin (KNDy) neurons of the arcuate nucleus (ARC) play a key role in the regulation of fertility. The ability to detect features of KNDy neurons that are essential for fertility may require three-dimensional (3D) imaging of the complete population. Recently developed protocols for optical tissue clearing permits 3D imaging of neuronal populations in un-sectioned brains. However, these techniques have largely been described in the mouse brain. We report 3D imaging of the KNDy cell population in the whole rat brain and sheep hypothalamus using immunolabelling and modification of a solvent-based clearing protocol, iDISCO. This study expands the use of …

Maternal Engineered Nanomaterial Inhalation During Gestation Alters The Fetal Transcriptome, P.A. Stapleton, Q.A. Hathaway, C.E. Nichols, A.B. Abukabda, M.V. Pinti, D.L. Shepherd, C.R. Mcbride, J. Yi, V.C. Castranova, J.M Hollander, Timothy Robert Nurkiewicz

Faculty & Staff Scholarship

Background: The integration of engineered nanomaterials (ENM) is well-established and widespread in clinical, commercial, and domestic applications. Cardiovascular dysfunctions have been reported in adult populations after exposure to a variety of ENM. As the diversity of these exposures continues to increase, the fetal ramifications of maternal exposures have yet to be determined. We, and others, have explored the consequences of ENM inhalation during gestation and identified many cardiovascular and metabolic outcomes in the F1 generation. The purpose of these studies was to identify genetic alterations in the F1 generation of Sprague-Dawley rats that result from maternal ENM inhalation during gestation. …

Macrophage Sensing Of Single- Walled Carbon Nanotubes Via Toll- Like Receptors, Sourav P. Mukherjee, Olesja Bondarenko, Pekka Kohonen, Fernando T. Andon, Tana Brzicova, Isabel Gessner, Sanjay Mathur, Massimo Bottini, Paolo Calligari, Lorenzo Stella, Elena Kisin, Anna Shvedova, Reija Autio, Heli Salminen-Mankonen, Ritta Lahesmaa, Bengt Fadeel

Faculty & Staff Scholarship

Carbon-based nanomaterials including carbon nanotubes (CNTs) have been shown to trigger

inflammation. However, how these materials are ‘sensed’ by immune cells is not known. Here we compared the effects of two carbon-based nanomaterials, single-walled CNTs (SWCNTs) and graphene oxide (GO), on primary human monocyte-derived macrophages. Genome-wide transcriptomics assessment was performed at sub-cytotoxic doses. Pathway analysis of the microarray data revealed pronounced effects on chemokine-encoding genes in macrophages exposed to SWCNTs, but not in response to GO, and these results were validated by multiplex array-based cytokine and chemokine profiling. Conditioned medium from SWCNT-exposed cells acted as a chemoattractant for dendritic cells. …

Absolute Lymphocyte And Neutrophil Counts In Neonatal Ischemic Brain Injury, Jessica M. Povroznik, Elizabeth B. Engler-Chiurazzi, Tania Nanavati, Paola Pergami

Faculty & Staff Scholarship

Objectives: This study aimed to identify differences in absolute neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio between neonates with two forms of ischemic brain injury, hypoxic-ischemic encephalopathy, and acute ischemic stroke, compared to controls. We also aimed to determine whether this neutrophil/lymphocyte response pattern is associated with disease severity or is a consequence of the effects of total-body cooling, an approved treatment for moderate-to-severe hypoxic-ischemic encephalopathy. Methods: A retrospective chart review of 101 neonates with hypoxic-ischemic encephalopathy + total-body cooling (n = 26), hypoxic-ischemic encephalopathy (n=12), acute ischemic stroke (n=15), and transient tachypnea of the newborn (n=48) was conducted; transient tachypnea of …

Hcn2 Channels In The Ventral Tegmental Area Regulate Behavioral Responses To Chronic Stress, Peng Zhong, Casey R. Vickstrom, Xiaojie Liu, Ying Hu, Laikang Yu, Han-Gang Yu, Qing-Song Liu

Faculty & Staff Scholarship

Dopamine neurons in the ventral tegmental area (VTA) are powerful regulators of depression-related behavior. Dopamine neuron activity is altered in chronic stress-based models of depression, but the underlying mechanisms remain incompletely understood. Here, we show that mice subject to chronic mild unpredictable stress (CMS) exhibit anxiety- and depressive-like behavior, which was associated with decreased VTA dopamine neuron firing in vivo and ex vivo. Dopamine neuron firing is governed by voltage-gated ion channels, in particular hyperpolarization- activated cyclic nucleotide-gated (HCN) channels. Following CMS, HCN-mediated currents were decreased in nucleus accumbens-projecting VTA dopamine neurons. Furthermore, shRNA-mediated HCN2 knockdown in the VTA was …

Prior Exposure To Corticosterone Markedly Enhances And Prolongs The Neuroinflammatory Response To Systemic Challenge With Lps, Kimberly A. Kelly, Lindsay T. Michalovicz, Julie V. Miller, Vincent Castranova, Diane B. Miller, James P. O'Callaghan

Faculty & Staff Scholarship

Systemic exposure to the inflammagen and bacterial endotoxin lipopolysaccharide (LPS) has been widely used to evaluate inflammation and sickness behavior. While many inflam- matory conditions occur in the periphery, it is well established that peripheral inflammation can affect the brain. Neuroinflammation, the elaboration of proinflammatory mediators in the CNS, commonly is associated with behavioral symptoms (e.g., lethargy, anhedonia, anorexia, depression, etc.) termed sickness behavior. Stressors have been shown to inter- act with and alter neuroinflammatory responses and associated behaviors. Here, we exam- ined the effects of the stress hormone, corticosterone (CORT), as a stressor mimic, on neuroinflammation induced with a …

A Functional Signature Ontology (Fusion) Screen Detects An Ampk Inhibitor With Selective Toxicity Toward Human Colon Tumor Cells, Binita Das, Beth K. Neilsen, Kurt W. Fisher, Drew Gehring, Youcai Hu, Deanna J. Volle, Hyun Seok Kim, Jamie L. Mccall, David L. Kelly, John B. Macmillian, Michael A. White, Robert E. Lewis

Faculty & Staff Scholarship

AMPK is a serine threonine kinase composed of a heterotrimer of a catalytic, kinase-containing α and regulatory β and γ subunits. Here we show that individual AMPK subunit expression and requirement for survival varies across colon cancer cell lines. While AMPKα1 expression is relatively consistent across colon cancer cell lines, AMPKα1 depletion does not induce cell death. Conversely, AMPKα2 is expressed at variable levels in colon cancer cells. In high expressing SW480 and moderate expressing HCT116 colon cancer cells, siRNA-mediated depletion induces cell death. These data suggest that AMPK kinase inhibition may be a useful component of future therapeutic strategies. …

Significant Inhibition Of Protein Binding Of Phenytoin, Sheril Alexander, Jesse Flores, Henrietta Ofuluozor, Mariana Babayeva

Touro College of Pharmacy (New York) Publications and Research

Aim: This research was aimed to assess the potential for inhibition of protein binding of phenytoin by tizoxanide in human plasma. Phenytoin was used because studies have proven to be a highly plasma protein-bound drug with a narrow therapeutic index and non-linear pharmacokinetics. Tizoxanide is another highly protein-bound active metabolite of an anti-infective prodrug nitazoxanide. Both drugs are expected to be administered together due to their therapeutic indications.

Study Design: The study was divided into two phases. Phase 1 produced a reference line of phenytoin protein binding values. Phase 2 was conducted to reveal the effect of the interactant tizoxanide …

Evaluation Of Bleeding And Thrombotic Risk In Patients Receiving Triple Antithrombotic Therapy, Katharine Lundy Pharmd, Elizabeth Meisberger Pharmd, Bcps, Kris Howard Pharmd, Bcps, Aacc, Jennifer Sposito Pharmd

Parkview Pharmacy Department

2018 ASHP Midyear Clinical Meeting / Anaheim, California / Poster # 11-309

Objective: Evaluate bleeding and thrombotic risk of patients receiving triple antithrombotic therapy (TAT) versus dual antithrombotic therapy (DAT) and characterize prescribing patterns.

Parent Perspectives On Health And Functioning Of School-Aged Adolescents With Disabilities, Gavin Colquit Edd, Cape, Cscs, Ashley D. Walker Phd, Ches, Moya L. Alfonso Phd, Msph, Maria Olivas Mph, Bethrand Ugwu Mph, Theophile Dipita Dr, Ph

United States Food and Drug Administration: Publications

BACKGROUND: Youth living with disabilities are at risk of experiencing poor health outcomes. Coordinated school health programs have an opportunity to help youth with disabilities and their families through health education, health services, and community engagement. The World Health Organization developed the International Classification of Functioning, Disability, and Health (ICF) as a framework to analyze factors related to health conditions. We used the ICF to examine parental perceptions of health and function among students with disabilities living in rural and urban areas.

METHODS: We surveyed parents (N = 71) using the parent-report versions of the Pediatric Outcomes Data Collection Instrument …

Mental Health Problems And Onset Of Tobacco Use Among 12- To 24-Year-Olds In The Path Study, Victoria R. Green Mhs, Kevin P. Conway Phd, Ches, Marushka L. Silveira Bds, Mph, Phd, Karin A. Kasza Ma, Amy Cohn Phd, K. Michael Cummings Phd, Mph, Cassandra A. Stanton Phd, Priscilla Callahan-Lyon Md, Wendy Slavit Mph, Ches, James D. Sargent Md, Nahla Hilmi Mph, Raymond S. Niaura Phd, Chad J. Reissig Phd, Elizabeth Lambert Ma, Izabella Zandberg Phd, Mary F. Brunette Md, Susanne E. Tanski Md, Nicolette Borek Phd, Andrew J. Hyland Phd, Wilson M. Compton Md, Mpe

United States Food and Drug Administration: Publications

Objective: To examine whether mental health problems predict incident use of 12 different tobacco products in a nationally representative sample of youth and young adults.

Method: This study analyzed Wave (W) 1 and W2 data from 10,533 12- to 24-year-old W1 never tobacco users in the Population Assessment of Tobacco and Health (PATH) Study. Self-reported lifetime internalizing and externalizing symptoms were assessed at W1. Past 12-month use of cigarettes, electronic nicotine delivery systems (ENDS), traditional cigars, cigarillos, filtered cigars, pipe, hookah, snus pouches, other smokeless tobacco, bidis and kreteks (youth only), and dissolvable tobacco was assessed at W2.

Results:In multivariable …

Etiology Of Teen Dating Violence Among Adolescent Children Of Alcoholics, Jennifer A. Livingston, Rina D. Eiden, Jared Lessard, Meghan Casey, James Henrie, Kenneth E. Leonard

United States Food and Drug Administration: Publications

Family processes in early life have been impli- cated in adolescent involvement in teen dating violence, yet the developmental pathways through which this occurs are not well understood. In this study, etiological pathways from parental psychopathology and marital conflict in infancy to involvement in dating violence in late adoles- cence were examined in a sample of children at high-risk due to parental alcohol problems. Families (N = 227) recruited when the child was 12 months of age were assessed at 12-, 24-, 36-months, kindergarten, 6th, 8th, and 12th grades. Slightly more than half of the children were female (51%) and …

Prevalence Of Adhd In Publicly Insured Adults, Yanmin Zhu, Wie Liu, Yan Li, Xi Wang, Almut G. Winterstein

United States Food and Drug Administration: Publications

Objective: To estimate the prevalence of adult ADHD diagnosis and treatment in U.S. Medicaid beneficiaries. Method: Using outpatient, inpatient, and pharmacy billing records for patients eligible for Medicaid fee-for-service benefits within 29 states from 1999 to 2010, we estimated the annual prevalence of ADHD diagnosis and treatment. Results: The prevalence of ADHD diagnosis increased from 2.20 per 1,000 patients in 1999 to 10.57 in 2010. Likewise, prevalence of ADHD treatment increased from 1.95 per 1,000 patients in 1999 to 13.16 in 2010. Between 40% and 65%, patients had ADHD drug prescription fills 6 months after ADHD diagnosis, whereas 45% to …

Statewide Cross-Sectional Survey Of Emergency Departments’ Adoption And Implementation Of The Ohio Opioid Prescribing Guidelines And Opioid Prescribing Practices, Jonathan Penm, Neil J. Mackinnon, Rebecca Mashni, Michael S. Lyons, Edmond A. Hooker, Erin L. Winstanley, Steve Carlton-Ford, Chloe Connelly, Erica Tolle, Jill Boone, Kathleen Koechlin, Jolene Defiore-Hyrmer

Faculty & Staff Scholarship

study objective: To evaluate the implementation of the Ohio Emergency and Acute Care Facility Opioids and Other Controlled Substances Prescribing Guidelines and their perceived impact on local policies and practice.

Methods: The study design was a cross-sectional survey of emergency department (ED) medical directors, or appropriate person identified by the hospital, perception of the impact of the Ohio ED Opioid Prescribing Guidelines on their departments practice. All hospitals with an ED in Ohio were contacted throughout October and November 2016. Distribution followed Dillman’s Tailored Design Method, augmented with telephone recruitment. Hospital chief executive officers were contacted when necessary to encourage …

Identifying Medication Management Smartphone App Features Suitable For Young Adults With Developmental Disabilities: Delphi Consensus Study, Teresa M. Salgado, Alexa Fedrigon, Donna Riccio Omichinski, Michelle A. Meade, Karen B. Farris

Pharmacotherapy and Outcomes Science Publications

Background: Smartphone apps can be a tool to facilitate independent medication management among persons with developmental disabilities. At present, multiple medication management apps exist in the market, but only 1 has been specifically designed for persons with developmental disabilities. Before initiating further app development targeting this population, input from stakeholders including persons with developmental disabilities, caregivers, and professionals regarding the most preferred features should be obtained.

Objective: The aim of this study was to identify medication management app features that are suitable to promote independence in the medication management process by young adults with developmental disabilities using a Delphi consensus …

Variability In Antifungal Utilization Among Neonatal, Pediatric, And Adult Inpatients In Academic Medical Centers Throughout The United States Of America, Jeremy S. Stultz, Rose Kohinke, Amy L. Pakyz

Pharmacotherapy and Outcomes Science Publications

Background
Identification of factors associated with antifungal utilization in neonatal, pediatric, and adult patient groups is needed to guide antifungal stewardship initiatives in academic medical centers.

Methods
For this hospital-level analysis, we analyzed antifungal use in hospitals across the United States of America, excluding centers only providing care for hematology/oncology patients. Analysis of variance was used to compare antifungal use between patient groups. Three multivariable linear regression models were used to determine independent factors associated with antifungal use in the neonatal, pediatric, and adult patient groups.

Results
For the neonatal, pediatric, and adult patient groups, 54, 44, and 60 hospitals …

The Humanistic And Economic Burden Associated With Anxiety And Depression Among Adults With Comorbid Diabetes And Hypertension, Kimberly Wallace, Xiaohui Zhao, Ranjita Misra, Usha Sambamoorthi

Faculty & Staff Scholarship

We conducted a retrospective cross-sectional study to estimate the humanistic and economic burden associated with depression and anxiety among adults with comorbid diabetes and hypertension. Pooled data from the 2013 and 2015 Medical Expenditure Panel Survey were used to include adults (≥18 years old) who were alive and diagnosed with both diabetes and hypertension during the observation period. We assessed the humanistic burden with health-related quality of life (HRQoL) and economic burden with the total annual healthcare expenditures. Depending on the presence/absence of depression and anxiety, the study sample was divided into four groups (i.e., no depression/anxiety, depression only, anxiety …

Evaluation Of Prothrombin Complex Concentrate Use In A Community Health System, Corissa L. Piatka Pharmd, Tim Johnston Pharmd, Bcps, Bcccp, Jim Roy Pharmd, Bcps, Bcccp

Parkview Pharmacy Department

Poster Presentation

2018 ASHP Midyear Clinical Meeting / Anaheim, California / Poster # 11-310

Objective: Evaluate by indication the appropriateness of prothrombin complex concentrate (PCC) use in a community health system.

Implementation Of A Pharmacist-Guided Procalcitonin Protocol In A Community Hospital, Jasmine Coatie Pharmd

Pharmacy Residency

Presentation given at Great Lakes Pharmacy Residency Conference 2018

State-Level Variability In Veteran Reliance On Veterans Health Administration And Potentially Preventable Hospitalizations: A Geospatial Analysis, Drew A. Helmer, Mazhgan Rowneki, Xue Feng, Chin-Lin Tseng, Danielle Rose, Orysya Soroka, Dennis Fried, Nisha Jani, Leonard M. Pogach, Usha Sambamoorthi

Faculty & Staff Scholarship

Most Veterans who use the Veterans Health Administration (VHA) also utilize private-sector health care providers. To better inform local and regional health care planning, we assessed the association between reliance on VHA ambulatory care and total and system-specific preventable hospitalization rates (PHRs) at the state level. We conducted a retrospective dynamic cohort study using Veterans with diabetes mellitus, aged 66 years or older, and dually enrolled in VHA and Medicare parts A and B from 2004 to 2010. While controlling for median age and proportion of males, we measured the association between reliance on VHA ambulatory care and PHRs at …