Medicine and Health Sciences Commons^™

Closed Head Injury In An Age-Related Alzheimer Mouse Model Leads To An Altered Neuroinflammatory Response And Persistent Cognitive Impairment, Scott J. Webster, Linda J. Van Eldik, D. Martin Watterson, Adam D. Bachstetter

Sanders-Brown Center on Aging Faculty Publications

Epidemiological studies have associated increased risk of Alzheimer's disease (AD)-related clinical symptoms with a medical history of head injury. Currently, little is known about pathophysiology mechanisms linked to this association. Persistent neuroinflammation is one outcome observed in patients after a single head injury. Neuroinflammation is also present early in relevant brain regions during AD pathology progression. In addition, previous mechanistic studies in animal models link neuroinflammation as a contributor to neuropathology and cognitive impairment in traumatic brain injury (TBI) or AD-related models. Therefore, we explored the potential interplay of neuroinflammatory responses in TBI and AD by analysis of the temporal …

When Operating On Dead People Saves Lives: Benefits Of Surgical Organ Donor Intensivists, Kristin Long, Cynthia Talley, Rebecca B. Yarrison, Andrew Bernard

Surgery Faculty Publications

Solid organ transplantation has emerged as a life-saving treatment for many patients suffering from end-stage organ failure. Organs have been successfully recovered after a variety of aggressive interventions. We propose that decompressive laparotomy, when clinically indicated, should be considered in the aggressive resuscitation of potential organ donors. A thorough literature review examining aggressive interventions on potential organ donors was conducted after experience with a unique case at this institution. Articles were reviewed for the types of interventions performed as well as the time frame in relation to organ donation. In our case, several ethical issues were raised when considering decompressive …

Identifying Cases Of Undiagnosed, Clinically Significant Copd In Primary Care: Qualitative Insight From Patients In The Target Population, Nancy K. Leidy, Katherine Kim, Elizabeth D. Bacci, Barbara P. Yawn, David M. Mannino, Byron M. Thomashow, R. Graham Barr, Stephen I. Rennard, Julia F. Houfek, Meilan K. Han, Catherine A. Meldrum, Barry J. Make, Russ P. Bowler, Anna W. Steenrod, Lindsey T. Murray, John W. Walsh, Fernando Martinez

Preventive Medicine and Environmental Health Faculty Publications

BACKGROUND: Many cases of chronic obstructive pulmonary disease (COPD) are diagnosed only after significant loss of lung function or during exacerbations.

AIMS: This study is part of a multi-method approach to develop a new screening instrument for identifying undiagnosed, clinically significant COPD in primary care.

METHODS: Subjects with varied histories of COPD diagnosis, risk factors and history of exacerbations were recruited through five US clinics (four pulmonary, one primary care). Phase I: Eight focus groups and six telephone interviews were conducted to elicit descriptions of risk factors for COPD, recent or historical acute respiratory events, and symptoms to inform the …

Strategies To Improve Medication Adherence In Patients With Schizophrenia: The Role Of Support Services, Peggy El-Mallakh, Jan Findlay

Nursing Faculty Publications

The purpose of this review is to describe research over the past 10 years on the role of support services in promoting medication adherence in mental health consumers diagnosed with schizophrenia. A literature search was conducted using the terms "medication adherence," "schizophrenia," and "support services," using Medline, PubMed, and CINAHL. Reference lists from published studies were also reviewed to identify additional research studies. Twenty-two articles focused on support-service intervention studies, and these were selected for review. Available support-service interventions include adherence therapy, electronic reminders via text messages and telephones, cognitive-behavioral and motivational strategies, and financial incentives. Support-service intervention strategies need …

What Did We Learn About Vads In 2014?, Maya Guglin

The VAD Journal

No abstract provided.

Targeting Human Central Nervous System Protein Kinases: An Isoform Selective P38Αmapk Inhibitor That Attenuates Disease Progression In Alzheimer's Disease Mouse Models, Saktimayee M. Roy, Valerie L. Grum-Tokars, James P. Schavocky, Faisal Saeed, Agnieszka Staniszewski, Andrew F. Teich, Ottavio Arancio, Adam D. Bachstetter, Scott J. Webster, Linda J. Van Eldik, George Minasov, Wayne F. Anderson, Jeffrey C. Pelletier, D. Martin Watterson

Spinal Cord and Brain Injury Research Center Faculty Publications

The first kinase inhibitor drug approval in 2001 initiated a remarkable decade of tyrosine kinase inhibitor drugs for oncology indications, but a void exists for serine/threonine protein kinase inhibitor drugs and central nervous system indications. Stress kinases are of special interest in neurological and neuropsychiatric disorders due to their involvement in synaptic dysfunction and complex disease susceptibility. Clinical and preclinical evidence implicates the stress related kinase p38αMAPK as a potential neurotherapeutic target, but isoform selective p38αMAPK inhibitor candidates are lacking and the mixed kinase inhibitor drugs that are promising in peripheral tissue disease indications have limitations for neurologic indications. Therefore, …

Chaperone Hsp47 Drives Malignant Growth And Invasion By Modulating An Ecm Gene Network, Jieqing Zhu, Gaofeng Xiong, Hanjiang Fu, B. Mark Evers, Binhua P. Zhou, Ren Xu

Markey Cancer Center Faculty Publications

The extracellular matrix (ECM) is a determining factor in the tumor microenvironment that restrains or promotes malignant growth. In this report, we show how the molecular chaperone protein Hsp47 functions as a nodal hub in regulating an ECM gene transcription network. A transcription network analysis showed that Hsp47 expression was activated during breast cancer development and progression. Hsp47 silencing reprogrammed human breast cancer cells to form growth-arrested and/or noninvasive structures in 3D cultures, and to limit tumor growth in xenograft assays by reducing deposition of collagen and fibronectin. Coexpression network analysis also showed that levels of microRNA(miR)-29b and -29c were …

Microcystins As Agents For Treatment Of Cancer, Noel R. Monks, Shuqian Liu, Jeffrey A. Moscow

Pharmaceutical Sciences Faculty Patents

This invention relates to the use of microcystins as agents for treatment of cancer. Also provided are methods of screening for microcystins with improved cytotoxicity.

Attenuation Of Traumatic Brain Injury-Induced Cognitive Impairment In Mice By Targeting Increased Cytokine Levels With A Small Molecule Experimental Therapeutic, Adam D. Bachstetter, Scott J. Webster, Danielle S. Goulding, Jonathan E. Morton, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Evidence from clinical studies and preclinical animal models suggests that proinflammatory cytokine overproduction is a potential driving force for pathology progression in traumatic brain injury (TBI). This raises the possibility that selective targeting of the overactive cytokine response, a component of the neuroinflammation that contributes to neuronal dysfunction, may be a useful therapeutic approach. MW151 is a CNS-penetrant, small molecule experimental therapeutic that selectively restores injury- or disease-induced overproduction of proinflammatory cytokines towards homeostasis. We previously reported that MW151 administered post-injury (p.i.) is efficacious in a closed head injury (CHI) model of diffuse TBI in mice. Here we test …

Perceptions Of School And Health Department Emergency Preparedness Collaboration, Kaitlin A. O'Keefe, Katharine D. Arrington, Michael Prelip, Kimberley I. Shoaf

Frontiers in Public Health Services and Systems Research

Background: School systems often have the vital responsibility of protecting students during emergency situations. Collaborations with the local health department (LHD) can be invaluable in helping schools effectively fulfill this responsibility.

Purpose: An evaluation of existing organizational collaborations is needed to describe attitudes toward current efforts and to form recommendations for enhancing the effectiveness of future joint programs.

Methods: Questionnaires regarding perceptions of existing collaborations were distributed to a sample of LHDs and schools districts in spring and summer 2011. Participant responses from each organization were paired on jurisdictional area, forming 25 paired observations. Analyses were conducted in …

Lipid-Induced Epigenomic Changes In Human Macrophages Identify A Coronary Artery Disease-Associated Variant That Regulates Ppap2b Expression Through Altered C/Ebp-Beta Binding, Michael E. Reschen, Kyle J. Gaulton, Da Lin, Elizabeth J. Soilleux, Andrew J. Morris, Susan S. Smyth, Christopher A. O'Callaghan

Gill Heart & Vascular Institute Faculty Publications

Genome-wide association studies (GWAS) have identified over 40 loci that affect risk of coronary artery disease (CAD) and the causal mechanisms at the majority of loci are unknown. Recent studies have suggested that many causal GWAS variants influence disease through altered transcriptional regulation in disease-relevant cell types. We explored changes in transcriptional regulation during a key pathophysiological event in CAD, the environmental lipid-induced transformation of macrophages to lipid-laden foam cells. We used a combination of open chromatin mapping with formaldehyde-assisted isolation of regulatory elements (FAIRE-seq) and enhancer and transcription factor mapping using chromatin immuno-precipitation (ChIP-seq) in primary human macrophages before …

Geographic Variation In The Delivery Of Public Health Services: Understanding Causes And Consequences, Glen P. Mays

Health Management and Policy Presentations

The implementation and reach of evidence-based prevention and public health programs varies widely across the U.S., as does the availability of cross-cutting infrastructure and foundational capabilities required to support these interventions. This talk profiles ongoing research to uncover the causes and consequences of variation in public health delivery. This research points to policy and administrative strategies that can reduce inequities and inefficiencies in public health protections.

Ba Da Ba Ba Ba: I’M Stealin’ It. Vietnam And Mccronyism, Rohit Sudarshan, Gizelle V. Gopez

Ex-Patt Magazine

McDonald’s just opened its first store in Vietnam. What does this mean for Southeast Asia’s 8th most populous country?

The Effects Of Antiepileptic Inducers In Neuropsychopharmacology, A Neglected Issue. Part I: A Summary Of The Current State For Clinicians, Jose De Leon

Psychiatry Faculty Publications

The literature on inducers in epilepsy and bipolar disorder is seriously contaminated by false negative findings. This is part i of a comprehensive review on antiepileptic drug (AED) inducers using both mechanistic pharmacological and evidence-based medicine to provide practical recommendations to neurologists and psychiatrists concerning how to control for them. Carbamazepine, phenobarbital and phenytoin, are clinically relevant AED inducers; correction factors were calculated for studied induced drugs. These correction factors are rough simplifications for orienting clinicians, since there is great variability in the population regarding inductive effects. As new information is published, the correction factors may need to be modified. …

Prescription Drug Monitoring Program Utilization In Kentucky Community Pharmacies, Sarah E. Wixson, Karen Blumenschein, Amie J. Goodin, Jeffery Talbert, Patricia R. Freeman

Pharmacy Practice and Science Faculty Publications

OBJECTIVE: Identify characteristics of Kentucky community pharmacists and community pharmacists' practice environment associated with utilization of the Kentucky All Schedule Prescription Electronic Reporting Program (KASPER).

METHODS: Surveys were mailed to all 1,018 Kentucky pharmacists with a KASPER account and an additional 1,000 licensed pharmacists without an account. Bivariate analyses examined the association between KASPER utilization and practice type (independent or chain) and practice location (rural or urban). A multivariate Poisson regression model with robust error variance estimated risk ratios (RR) of KASPER utilization by characteristics of pharmacists' practice environment.

RESULTS: Responses were received from 563 pharmacists (response …

Apparent Role For Borrelia Burgdorferi Luxs During Mammalian Infection, William K. Arnold, Christina R. Savage, Alyssa D. Antonicello, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The Lyme disease spirochete, Borrelia burgdorferi, controls protein expression patterns during its tick-mammal infection cycle. Earlier studies demonstrated that B. burgdorferi synthesizes 4,5-dihydroxy-2,3-pentanedione (autoinducer-2 [AI-2]) and responds to AI-2 by measurably changing production of several infection-associated proteins. luxS mutants, which are unable to produce AI-2, exhibit altered production of several proteins. B. burgdorferi cannot utilize the other product of LuxS, homocysteine, indicating that phenotypes of luxS mutants are not due to the absence of that molecule. Although a previous study found that a luxS mutant was capable of infecting mice, a critical caveat to those results is that bacterial …

A Randomized Controlled Prospective Study Comparing A Low Dose Bupivacaine And Fentanyl Mixture To A Conventional Dose Of Hyperbaric Bupivacaine For Cesarean Section, Himabindu Gandam Venkata, Surender Pasupuleti, Upender Gowd Pabba, Sridevi Porika, Goutham Talari

Internal Medicine Faculty Publications

CONTEXT: Hormonal and mechanical factors make obstetric patients need strict dose calculations of local anesthetics intrathecally for spinal anesthesia. Any greater dose of local anesthetics can cause hemodynamic instability, maternal morbidity and any lesser dose can produce inadequate block. Hence, we hypothesized in our study that by using low dose of bupivacaine with fentanyl can maintain stable hemodynamics and provide better analgesia.

AIM: The aim was to compare the hemodynamics and duration of analgesia using a low dose (7.5 mg) bupivacaine fentanyl mixture to a conventional dose (10 mg) of hyperbaric bupivacaine for cesarean section.

SETTINGS AND DESIGN …

Transylvania University And Its Hemp Connection, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

No abstract provided.

Fatalistic Beliefs And Completion Of The Hpv Vaccination Series Among A Sample Of Young Appalachian Kentucky Women, Robin C. Vanderpool, Emily Van Meter Dressler, Lindsay R. Stradtman, Richard A. Crosby

Health, Behavior & Society Faculty Publications

PURPOSE: Uptake and completion of the 3-dose human papillomavirus (HPV) vaccine is important for the primary prevention of cervical cancer. However, HPV vaccination rates among adolescent females and young women remain low in certain geographic areas of the United States, including Appalachia. Although greater fatalistic beliefs have been previously associated with lower rates of preventive cancer behaviors among adults, little research exists on the impact of fatalism on HPV vaccination behaviors, especially among younger individuals. Therefore, the purpose of this study was to examine the association between fatalistic beliefs and completion of the full HPV vaccine series among young women, …

Is Psychiatry Only Neurology? Or Only Abnormal Psychology? Déjà Vu After 100 Years, Jose De Leon

Psychiatry Faculty Publications

Forgetting history, which frequently repeats itself, is a mistake. In General Psychopathology, Jaspers criticised early 20th century psychiatrists, including those who thought psychiatry was only neurology (Wernicke) or only abnormal psychology (Freud), or who did not see the limitations of the medical model in psychiatry (Kraepelin). Jaspers proposed that some psychiatric disorders follow the medical model (Group I), while others are variations of normality (Group III), or comprise schizophrenia and severe mood disorders (Group II). In the early 21st century, the players' names have changed but the game remains the same. The US NIMH is reprising both Wernicke's brain mythology …

Detection Of Phlpp1Α/Β In Human And Mouse Brain By Different Anti-Phlpp1 Antibodies, Travis C. Jackson, Hülya Bayir, Milos D. Ikonomovic, Keri Janesko-Feldman, Zaichuan Mi, Tianyan Gao, Edwin K. Jackson, Patrick M. Kochanek

Markey Cancer Center Faculty Publications

Pleckstrin homology domain and leucine rich repeat protein phosphatase 1 (PHLPP1) is a member of the serine/threonine family of phosphatases. It has been studied in organs including brain, heart, pancreas, adipose, breast, and prostate. Human PHLPP1 encodes two splice variants - PHLPP1α (~140-150 kDa) and PHLPP1β (~180-190 kDa). Commercial antibodies are widely used to characterize PHLPP1 proteins in cells/tissues. Here we validate five different antibodies to detect PHLPP1α/β by Western blot using PHLPP1 WT/KO mice. All antibodies recognize PHLPP1β in brain. Only a single antibody (Cosmo Bio Co) detects PHLPP1α (~145-150 kDa). The other four antibodies detect a non-specific signal …

G9a Is Essential For Emt-Mediated Metastasis And Maintenance Of Cancer Stem Cell-Like Characters In Head And Neck Squamous Cell Carcinoma, Shuli Liu, Dongxia Ye, Wenzheng Guo, Wenwen Yu, Yue He, Jingzhou Hu, Yanan Wang, Ling Zhang, Yueling Liao, Hongyong Song, Shuangshuang Zhong, Dongliang Xu, Huijing Yin, Beibei Sun, Xiaofei Wang, Jingyi Liu, Yadi Wu, Binhua P. Zhou, Zhiyuan Zhang, Jiong Deng

Markey Cancer Center Faculty Publications

Head and neck squamous cell carcinoma (HNSCC) is a particularly aggressive cancer with poor prognosis, largely due to lymph node metastasis and local recurrence. Emerging evidence suggests that epithelial-to-mesenchymal transition (EMT) is important for cancer metastasis, and correlated with increased cancer stem cells (CSCs) characteristics. However, the mechanisms underlying metastasis to lymph nodes in HNSCC is poorly defined. In this study, we show that E-cadherin repression correlates with cancer metastasis and poor prognosis in HNSCC. We found that G9a, a histone methyltransferase, interacts with Snail and mediates Snail-induced transcriptional repression of E-cadherin and EMT, through methylation of histone H3 lysine-9 …

Immune Function And Muscle Adaptations To Resistance Exercise In Older Adults: Study Protocol For A Randomized Controlled Trial Of A Nutritional Supplement, Richard A. Dennis, Usha Ponnappan, Ralph L. Kodell, Kimberly K. Garner, Christopher M. Parkes, Melinda M. Bopp, Kalpana P. Padala, Charlotte A. Peterson, Prasad R. Padala, Dennis H. Sullivan

Physical Therapy Faculty Publications

BACKGROUND: Immune function may influence the ability of older adults to maintain or improve muscle mass, strength, and function during aging. Thus, nutritional supplementation that supports the immune system could complement resistance exercise as an intervention for age-associated muscle loss. The current study will determine the relationship between immune function and exercise training outcomes for older adults who consume a nutritional supplement or placebo during resistance training and post-training follow-up. The supplement was chosen due to evidence suggesting its ingredients [arginine (Arg), glutamine (Gln), and β-hydroxy β-methylbutyrate (HMB)] can improve immune function, promote muscle growth, and counteract muscle loss. …

Ppm1a Regulates Antiviral Signaling By Antagonizing Tbk1-Mediated Sting Phosphorylation And Aggregation, Zexing Li, Ge Liu, Liwei Sun, Yan Teng, Xuejiang Guo, Jianhang Jia, Jiahao Sha, Xiao Yang, Dahua Chen, Qinmiao Sun

Markey Cancer Center Faculty Publications

Stimulator of interferon genes (STING, also known as MITA and ERIS) is critical in protecting the host against DNA pathogen invasion. However, the molecular mechanism underlying the regulation of STING remains unclear. Here, we show that PPM1A negatively regulates antiviral signaling by targeting STING in its phosphatase activity-dependent manner, and in a line with this, PPM1A catalytically dephosphorylates STING and TBK1 in vitro. Importantly, we provide evidence that whereas TBK1 promotes STING aggregation in a phosphorylation-dependent manner, PPM1A antagonizes STING aggregation by dephosphorylating both STING and TBK1, emphasizing that phosphorylation is crucial for the efficient activation of STING. Our …

Connecting Preparedness Science With The National Health Security Preparedness Index: Research Translation Opportunities, Glen P. Mays

Health Management and Policy Presentations

The National Health Security Preparedness Index is a mechanism for applying advances in preparedness measurement and analysis from Hurricane Sandy research projects to advance policies and practices in preparing for, responding to, and recovering from disasters and other health emergencies

The National Health Security Preparedness Index: Harnessing Evidence & Experience To Drive Improvement, Glen P. Mays

Health Management and Policy Presentations

This presentation profiles the National Health Security Preparedness Index as a mechanism for measuring preparedness and resiliency levels across the U.S. Forthcoming enhancements in measurement and analytic methodologies will allow the Index to play heightened roles in informing policies and practices that protect the U.S. population from a broad range of hazards.

Rear-Facing Child Car Seats: Are Laws Requiring Them Effective?, Eli Friedman, Henry J. Carretta, Joshua Jordan, Leslie M. Beitsch

Frontiers in Public Health Services and Systems Research

Introduction: Motor vehicle crashes are a leading cause of death in children aged ≤ 2 years in the U.S. The American Academy of Pediatrics advised that children should remain in rear-facing child car seats to mitigate injury from the most common type of severe collision (frontal). Several states have passed laws following these recommendations.

Methods: In 2013 publicly available statutes and comprehensive motor vehicle fatality data from the National Highway Traffic Safety Administration’s Fatality Analysis Reporting System database were used to investigate whether there is a relationship between motor vehicle crash fatality rates for children under 1 year of age …

Answering The Call To Integrate: Simple Strategies From Public Health And Healthcare Executives In One Urban County, Erik L. Carlton, Paul C. Erwin

Frontiers in Public Health Services and Systems Research

Background: As the Affordable Care Act transforms the practice of both public health and health care, it also provides opportunity for both to become more closely linked through improved integration and collaboration. Yet, while public health agencies are increasingly called to work with healthcare partners to address population health needs, both public health leaders and their healthcare counterparts may not be well equipped to answer that call. Although recent studies have begun exploring the collaborative strategies and capacity of public health system partners, there is still much to learn. The purpose of this study was to identify, through the perspective …

Accreditation Intent, Community Health Assessments, And Local Health Department–Hospital Collaboration, Erik L. Carlton, Simone Singh

Frontiers in Public Health Services and Systems Research

Background: Community health assessments (CHAs) are among the most core of activities conducted by local health departments (LHDs), and many LHDs have been conducting CHAs on a regular basis for years. More recently, completing a CHA has also become a prerequisite for LHDs seeking accreditation by the Public Health Accreditation Board (PHAB). Similarly, under the Affordable Care Act, tax-exempt hospitals are required to conduct periodic community health needs assessments. Opportunities thus exist for LHDs and tax-exempt hospitals to engage in collaborations related to CHAs. Yet, it remains unclear whether interest in PHAB accreditation provides incentive to LHDs to engage in …

Cystic Multiglandular Maternal Hyperparathyroidism Diagnosed By Neonatal Hypocalcemic Seizures, Kristin Long, Tessa Cartwright, David A. Sloan, Cortney Y. Lee

Surgery Faculty Publications

A 7-day-old male infant born to a healthy 33-year-old female at 37 weeks of gestation was brought to the local emergency department (ED) with sudden-onset tonic-clonic seizures. Laboratory testing revealed extreme hypocalcemia (ionized calcium of 3.2 mg/dl) and undetectable parathyroid hormone (PTH/ml). Concomitant evaluation of the mother revealed both elevated ionized calcium (5.9 mg/dl) and PTH (116 pg/ml). The mother underwent preoperative ultrasound localization and sestamibi scan, followed promptly by parathyroidectomy. Given the cystic appearance and presence of multiglandular disease, evaluation for familial cystic parathyroid adenomatosis (hyperparathyroidism-jaw bone-tumor syndrome) and MEN 1 were undertaken. The infant was stabilized and discharged …