Medicine and Health Sciences Commons^™

Variation In Competence For Zikv Transmission By Aedes Aegypti And Aedes Albopictus In Mexico, Selene M. Garcia-Luna, James Weger-Lucarelli, Claudia Rückert, Reyes A. Murrieta, Michael C. Young, Alex D. Byas, Joseph R. Fauver, Rushika Perera, Adriana E. Flores-Suarez, Gustavo Ponce-Garcia, Americo D. Rodriguez, Gregory D. Ebel, William C. Black

Journal Articles: Epidemiology

BACKGROUND: ZIKV is a new addition to the arboviruses circulating in the New World, with more than 1 million cases since its introduction in 2015. A growing number of studies have reported vector competence (VC) of Aedes mosquitoes from several areas of the world for ZIKV transmission. Some studies have used New World mosquitoes from disparate regions and concluded that these have a variable but relatively low competence for the Asian lineage of ZIKV.

METHODOLOGY/PRINCIPAL FINDINGS: Ten Aedes aegypti (L) and three Ae. albopictus (Skuse) collections made in 2016 from throughout Mexico were analyzed for ZIKV (PRVABC59-Asian lineage) VC. Mexican …

Searching For Novel Biomarkers Using A Mouse Model Of Cln3-Batten Disease, Derek Timm, Jacob T. Cain, Ryan D. Geraets, Katherine A. White, Seung Yon Koh, Tammy Kielian, David A. Pearce, Michelle L. Hastings, Jill M. Weimer

Journal Articles: Pathology and Microbiology

CLN3-Batten disease is a rare, autosomal recessive disorder involving seizures, visual, motor and cognitive decline, and premature death. The Cln3Δex7/8 mouse model recapitulates several phenotypic characteristics of the most common 1.02kb disease-associated deletion. Identification of reproducible biomarker(s) to facilitate longitudinal monitoring of disease progression and provide readouts for therapeutic response has remained elusive. One factor that has complicated the identification of suitable biomarkers in this mouse model has been that variations in animal husbandry appear to significantly influence readouts. In the current study, we cross-compared a number of biological parameters in blood from Cln3Δex7/8 mice and control, non-disease mice on …

Centrilobular Emphysema And Coronary Artery Calcification: Mediation Analysis In The Spiromics Cohort, Surya P. Bhatt, Hrudaya P. Nath, Young-Il Kim, Rekha Ramachandran, Jubal R. Watts, Nina L.J. Terry, Sushil Sonavane, Swati P. Deshmane, Prescott G. Woodruff, Elizabeth C. Oelsner, Sandeep Bodduluri, Meilan K. Han, Wassim W. Labaki, J. Michael Wells, Fernando J. Martinez, R. Graham Barr, Mark T. Dransfield, Spiromics Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with a two-to-five fold increase in the risk of coronary artery disease independent of shared risk factors. This association is hypothesized to be mediated by systemic inflammation but this link has not been established.

METHODS: We included 300 participants enrolled in the SPIROMICS cohort, 75 each of lifetime non-smokers, smokers without airflow obstruction, mild-moderate COPD, and severe-very severe COPD. We quantified emphysema and airway disease on computed tomography, characterized visual emphysema subtypes (centrilobular and paraseptal) and airway disease, and used the Weston visual score to quantify coronary artery calcification (CAC). We used …

Can Capture Be Used To Identify Undiagnosed Patients With Mild-To-Moderate Copd Likely To Benefit From Treatment?, Nancy K. Leidy, Fernando J. Martinez, Karen G. Malley, David M. Mannino, Meilan K. Han, Elizabeth D. Bacci, Randall W. Brown, Julia F. Houfek, Wassim W. Labaki, Barry J. Make, Catherine A. Meldrum, Wilson Quezada, Stephen I. Rennard, Byron Thomashow, Barbara P. Yawn

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE™) uses five questions and peak expiratory flow (PEF) thresholds (males ≤350 L/min; females ≤250 L/min) to identify patients with a forced expiratory volume in 1 second (FEV

METHODS: Data from the CAPTURE development study were used to test its sensitivity (SN) and specificity (SP) differentiating mild-to-moderate COPD (n=73) from no COPD (n=87). SN and SP for differentiating all COPD cases (mild to severe; n=259) from those without COPD (n=87) were also estimated. The modified Medical Research Council (mMRC) dyspnea scale and COPD Assessment Test (CAT™) …

Adherence And Perceived Barriers To Oral Antiviral Therapy For Chronic Hepatitis B, Kerui Xu, Li-Ming Liu, Evi A. Farazi, Hongmei Wang, Fedja A. Rochling, Shinobu Watanabe-Galloway, Jian-Jun Zhang

Journal Articles: Epidemiology

BACKGROUND: Globally, of the 248 million people chronically infected with the hepatitis B virus (HBV), 74 million reside in China. Five oral nucleot(s)ide analogs (NUCs) have been approved for the treatment of chronic hepatitis B (CHB) in China.

OBJECTIVES: The aims of this study were to determine rates of adherence to NUC therapy in patients with CHB, to identify the self-perceived barriers to adherence, and to examine the factors associated with adherence.

METHODS: Questionnaire-based interviews were administered among Chinese patients with CHB at hepatology clinics of a tertiary hospital in the city of Wuhan, China. Adults aged 18 years or …

Preliminary Studies On Immune Response And Viral Pathogenesis Of Zika Virus In Rhesus Macaques, Shawna M. Woollard, Omalla A. Olwenyi, Debashis Dutta, Rajnish S. Dave, Saumi Mathews, Santhi Gorantla, Noel Johnson, Luis Giavedoni, Robert B. Norgren, Siddappa N. Byrareddy

Journal Articles: Genetics, Cell Biology & Anatomy

Zika Virus (ZIKV) is primarily transmitted through mosquito bites. It can also be transmitted during sexual intercourse and in utero from mother to fetus. To gain preliminary insight into ZIKV pathology and immune responses on route of transmission, rhesus macaques (RMs) were inoculated with ZIKV (PRVABC59) via intravaginal (IVAG) (n = 3) or subcutaneous (sub Q) (n = 2) routes. Systemic ZIKV infection was observed in all RMs, regardless of the route of inoculation. After 9 days postinfection (dpi), ZIKV was not detected in the plasma of IVAG- and sub-Q-inoculated RMs. Importantly, RMs harbored ZIKV up to 60 …

Characterization Of Cdk(5) Inhibitor, 20-223 (Aka Cp668863) For Colorectal Cancer Therapy, Caroline M. Robb, Smit Kour, Jacob I. Contreras, Ekta Agarwal, Carter J. Barger, Sandeep Rana, Yogesh Sonawane, Beth K. Neilsen, Margaret Taylor, Smitha Kizhake, Rhishikesh N. Thakare, Sanjib Chowdhury, Jing Wang, Jennifer D. Black, Michael A. Hollingsworth, Michael G. Brattain, Amarnath Natarajan

Journal Articles: Biochemistry & Molecular Biology

Colorectal cancer (CRC) remains one of the leading causes of cancer related deaths in the United States. Currently, there are limited therapeutic options for patients suffering from CRC, none of which focus on the cell signaling mechanisms controlled by the popular kinase family, cyclin dependent kinases (CDKs). Here we evaluate a Pfizer developed compound, CP668863, that inhibits cyclin-dependent kinase 5 (CDK5) in neurodegenerative disorders. CDK5 has been implicated in a number of cancers, most recently as an oncogene in colorectal cancers. Our lab synthesized and characterized CP668863 – now called 20-223. In our established colorectal cancer xenograft model, 20-223 reduced …

Phosphoinositide 3-Kinase Signaling Pathway In Pancreatic Ductal Adenocarcinoma Progression, Pathogenesis, And Therapeutics, Divya Murthy, Kuldeep S. Attri, Pankaj K. Singh

Journal Articles: Eppley Institute

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by its sudden manifestation, rapid progression, poor prognosis, and limited therapeutic options. Genetic alterations in key signaling pathways found in early pancreatic lesions are pivotal for the development and progression of pancreatic intraepithelial neoplastic lesions into invasive carcinomas. More than 90% of PDAC tumors harbor driver mutations in K-Ras that activate various downstream effector-signaling pathways, including the phosphoinositide-3-kinase (PI3K) pathway. The PI3K pathway also responds to stimuli from various growth factor receptors present on the cancer cell surface that, in turn, modulate downstream signaling cascades. Thus, the inositide signaling acts …

Aminoglycosides Rapidly Inhibit Nad(P)H Metabolism Increasing Reactive Oxygen Species And Cochlear Cell Demise, Danielle E. Desa, Michael G. Nichols, Heather Jensen Smith

Journal Articles: Eppley Institute

Despite causing permanent hearing loss by damaging inner ear sensory cells, aminoglycosides (AGs) remain one of the most widely used classes of antibiotics in the world. Although the mechanisms of cochlear sensory cell damage are not fully known, reactive oxygen species (ROS) are clearly implicated. Mitochondrial-specific ROS formation was evaluated in acutely cultured murine cochlear explants exposed to gentamicin (GM), a representative ototoxic AG antibiotic. Superoxide (O2·-) and hydrogen peroxide (H2O2) were measured using MitoSOX Red and Dihydrorhodamine 123, respectively, in sensory and supporting cells. A 1-h GM exposure significantly increased O2·- formation in IHCs and increased H2O2 formation in …

Met Receptor Inhibitor Su11274 Localizes In The Endoplasmic Reticulum, Edwin J. Wiest, Heather Jensen Smith, Michael A. Hollingsworth

Journal Articles: Eppley Institute

We discovered that SU11274, a class I c-Met inhibitor, fluoresces when excited by 488 nm laser light and showed rapid specific accumulation in distinct subcellular compartments. Given that SU11274 reduces cancer cell viability, we exploited these newly identified spectral properties to determine SU11274 intracellular distribution and accumulation in human pancreatic cancer cells. The aim of the studies reported here was to identify organelle(s) to which SU11274 is trafficked. We conclude that SU11274 rapidly and predominantly accumulates in the endoplasmic reticulum.

Abnormal T Cell Frequencies, Including Cytomegalovirus-Associated Expansions, Distinguish Seroconverted Subjects At Risk For Type 1 Diabetes, Robert Z. Harms, Kristina M. Lorenzo-Arteaga, Katie R. Ostlund, Victoria B. Smith, Lynette M. Smith, Peter Gottlieb, Nora Sarvetnick

Journal Articles: Surgery

We analyzed T cell subsets from cryopreserved PBMC obtained from the TrialNet Pathway to Prevention archives. We compared subjects who had previously seroconverted for one or more autoantibodies with non-seroconverted, autoantibody negative individuals. We observed a reduced frequency of MAIT cells among seroconverted subjects. Seroconverted subjects also possessed decreased frequencies of CCR4-expressing CD4 T cells, including a regulatory-like subset. Interestingly, we found an elevation of CD57+, CD28-, CD127-, CD27- CD8 T cells (SLEC) among seroconverted subjects that was most pronounced among those that progressed to disease. The frequency of these SLEC was strongly correlated with CMV IgG abundance among seroconverted …

Inter-Vendor Reproducibility Of Left And Right Ventricular Cardiovascular Magnetic Resonance Myocardial Feature-Tracking, Roman Johannes Gertz, Torben Lange, Johannes Tammo Kowallick, Sören Jan Backhaus, Michael Steinmetz, Wieland Staab, Shelby Kutty, Gerd Hasenfuß, Joachim Lotz, Andreas Schuster

Journal Articles: Cardiology

AIM: Since cardiovascular magnetic resonance feature-tracking (CMR-FT) has been demonstrated to be of incremental clinical merit we investigated the interchangeability of global left and right ventricular strain parameters between different CMR-FT software solutions.

MATERIAL AND METHODS: CMR-cine images of 10 patients without significant reduction in LVEF and RVEF and 10 patients with a significantly impaired systolic function were analyzed using two different types of FT-software (TomTec, Germany; QStrain, Netherlands). Global longitudinal strains (LV GLS, RV GLS), global left ventricular circumferential (GCS) and radial strains (GRS) were assessed. Differences in intra- and inter-observer variability within and between software types based on …

Direct Conversion Of Mouse Astrocytes Into Neural Progenitor Cells And Specific Lineages Of Neurons, Kangmu Ma, Xiaobei Deng, Xiaohuan Xia, Zhaohuan Fan, Xinrui Qi, Yongxiang Wang, Yuju Li, Yizhao Ma, Qiang Chen, Hui Peng, Jianqing Ding, Chunhong Li, Yunlong Huang, Changhai Tian, Jialin C. Zheng

Journal Articles: Cellular & Integrative Physiology

Background: Cell replacement therapy has been envisioned as a promising treatment for neurodegenerative diseases. Due to the ethical concerns of ESCs-derived neural progenitor cells (NPCs) and tumorigenic potential of iPSCs, reprogramming of somatic cells directly into multipotent NPCs has emerged as a preferred approach for cell transplantation.

Methods: Mouse astrocytes were reprogrammed into NPCs by the overexpression of transcription factors (TFs) Foxg1, Sox2, and Brn2. The generation of subtypes of neurons was directed by the force expression of cell-type specific TFs Lhx8 or Foxa2/Lmx1a.

Results: Astrocyte-derived induced NPCs (AiNPCs) share high similarities, including the expression of NPC-specific genes, DNA methylation …

Novel Antioxidant Properties Of Doxycycline, Dahn L. Clemens, Michael J. Duryee, Cleofes Sarmiento, Andrew Chiou, Jacob D. Mcgowan, Carlos D. Hunter, Sarah L. Schlichte, Jun Tian, Lynell W. Klassen, James R. O'Dell, Geoffrey M. Thiele, Ted R. Mikuls, Matthew C. Zimmerman, Daniel R. Anderson

Journal Articles: Cellular & Integrative Physiology

Doxycycline (DOX), a derivative of tetracycline, is a broad-spectrum antibiotic that exhibits a number of therapeutic activities in addition to its antibacterial properties. For example, DOX has been used in the management of a number of diseases characterized by chronic inflammation. One potential mechanism by which DOX inhibits the progression of these diseases is by reducing oxidative stress, thereby inhibiting subsequent lipid peroxidation and inflammatory responses. Herein, we tested the hypothesis that DOX directly scavenges reactive oxygen species (ROS) and inhibits the formation of redox-mediated malondialdehyde-acetaldehyde (MAA) protein adducts. Using a cell-free system, we demonstrated that DOX scavenged reactive oxygen …

Elevated Pressure Increases Ca2+ Influx Through Ampa Receptors In Select Populations Of Retinal Ganglion Cells, Xiangyi Wen, Asia L. Cahill, Cody Barta, Wallace B. Thoreson, Scott Nawy

Journal Articles: Ophthalmology

The predominate type of AMPA receptor expressed in the CNS is impermeable to Ca²⁺ (CI-AMPAR). However, some AMPA receptors are permeable to Ca²⁺ (CP-AMPAR) and play important roles in development, plasticity and disease. In the retina, ganglion cells (RGCs) are targets of disease including glaucoma and diabetic retinopathy, but there are many types of RGCs and not all types are targeted equally. In the present study, we sought to determine if there are differences in expression of AMPARs amongst RGC subtypes, and if these differences might contribute to differential vulnerability in a model of stress. Using cultured RGCs …

Health And Appearance Reasons For Weight Loss As Predictors Of Long-Term Weight Change, Joseph E. Mroz, Carol H. Pullen, Patricia A. Hageman

Journal Articles: Physical Therapy

This study investigated whether women's initial reasons (health, appearance to others, or appearance to self) for wanting to lose weight influenced their weight change over a 30-month web-based intervention. Multilevel modeling with 1416 observations revealed that only appearance in relation to one's self was a significant (negative) predictor. Women highly motivated to lose weight to improve their appearance in relation to themselves gained weight at 30 months, whereas those not motivated for this reason achieved clinically significant weight loss. Results suggest examining participants' initial reasons for weight loss as an important component of intervention failure or success.

Temporal And Geospatial Trends Of Pediatric Cancer Incidence In Nebraska Over A 24-Year Period, Evi A. Farazi, Shinobu Watanabe-Galloway, L. Westman, B. Rettig, P. Hunt, R. Cammack, John W. Sparks, Don W. Coulter

Journal Articles: Epidemiology

BACKGROUND: Data from the Surveillance, Epidemiology, and End Results (SEER) revealed that the incidence of pediatric cancer in Nebraska exceeded the national average during 2009-2013. Further investigation could help understand these patterns.

METHODS: This retrospective cohort study investigated pediatric cancer (0-19 years old) age adjusted incidence rates (AAR) in Nebraska using the Nebraska Cancer Registry. SEER AARs were also calculated as a proxy for pediatric cancer incidence in the United States (1990-2013) and compared to the Nebraska data. Geographic Information System (GIS) mapping was also used to display the spatial distribution of cancer in Nebraska at the county level. Finally, …

Absolute Oral Bioavailability Of Creatine Monohydrate In Rats: Debunking A Myth, Eman A. Alraddadi, Ryan Lillico, Jonathan L. Vennerstrom, Ted M. Lakowski, Donald W. Miller

Journal Articles: Pharmaceutical Sciences

Creatine is an ergogenic compound used by athletes to enhance performance. Supplementation with creatine monohydrate (CM) has been suggested for musculoskeletal and neurological disorders. Until now, little is known about its pharmacokinetic profile. Our objective was to determine the oral bioavailability of CM and the influence of dose on oral absorption. Rats were dosed orally with low dose (10 mg/kg) or high dose (70 mg/kg)

The Enzymatic Activity Of Apobe3g Multimers, Yangang Pan, Karen Zagorski, Luda S. Shlyakhtenko, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

APOBEC3G (A3G) belongs to the family of cytosine deaminases that play an important role in the innate immune response. Similar to other, two-domain members of the APOBEC family, A3G is prone to concentration-dependent oligomerization, which is an integral for its function in the cell. It is shown that oligomerization of A3G is related to the packing mechanism into virus particle and, is critical for the so-called roadblock model during reverse transcription of proviral ssDNA. The role of oligomerization for deaminase activity of A3G is widely discussed in the literature; however, its relevance to deaminase activity for different oligomeric forms of …

Flupirtine Derivatives As Potential Treatment For The Neuronal Ceroid Lipofuscinoses, Joelle Makoukji, Fadi Saadeh, Karl Albert Mansour, Sally El-Sitt, Jamal Al Ali, Nihar Kinarivala, Paul C. Trippier, Rose-Mary Boustany

Journal Articles: Pharmaceutical Sciences

OBJECTIVE: Neuronal Ceroid Lipofuscinoses (NCL) are fatal inherited neurodegenerative diseases with established neuronal cell death and increased ceramide levels in brain, hence, a need for disease-modifying drug candidates, with potential to enhance growth, reduce apoptosis and lower ceramide in neuronal precursor PC12 cells and human NCL cell lines using enhanced flupirtine aromatic carbamate derivatives in vitro.

METHODS: Aromatic carbamate derivatives were tested by establishing growth curves under pro-apoptotic conditions and activity evaluated by trypan blue and JC-1 staining, as well as a drop in pro-apoptotic ceramide in neuronal precursor PC12 cells following siRNA knockdown of the

RESULTS: Retigabine, the benzyl-derivatized …

Building A Bigger Tent In Point-Of-Care Ultrasound Education: A Mixed-Methods Evaluation Of Interprofessional, Near-Peer Teaching Of Internal Medicine Residents By Sonography Students, Christopher J. Smith, Tabatha Matthias, Elizabeth Beam, Kathryn Wampler, Lea Pounds, Devin Nickol, Kristy Carlson, Kim Michael

Journal Articles: Diagnostic Medical Sonography

BACKGROUND: Point-of-care-ultrasound (POCUS) training is expanding in undergraduate and graduate medical education, but lack of trained faculty is a major barrier. Two strategies that may help mitigate this obstacle are interprofessional education (IPE) and near-peer teaching. The objective of this study was to evaluate a POCUS course in which diagnostic medical sonography (DMS) students served as near-peer teachers for internal medicine residents (IMR) learning to perform abdominal sonography.

METHODS: Prior to the IPE workshop, DMS students participated in a train-the-trainer session to practice teaching and communication skills via case-based simulation. DMS students then coached first-year IMR to perform POCUS examinations …

Microrna Cluster Mir199a/214 Are Differentially Expressed In Female And Male Rats Following Nicotine Self-Administration, Steven T. Pittenger, Victoria L. Schaal, Dalia Moore, Rahul S. Guda, Sneh Koul, Sowmya V. Yelamanchili, Rick A. Bevins, Gurudutt Pendyala

Journal Articles: Pharmacology & Experimental Neuroscience

Previous research has established sex differences associated with nicotine intake, however a significant gap in knowledge remains regarding the molecular mechanisms that govern these differences at the transcriptional level. One critical regulator of transcription are microRNAs (miRNAs). miRNAs are a family of non-coding RNAs that regulate an array of important biological functions altered in several disease states, including neuroadaptive changes within the brain associated with drug dependence. We examined the prefrontal cortex (PFC) from male and female Sprague-Dawley rats following self-administration (22 days) of nicotine or yoked saline controls using next generation RNA-Sequencing (RNA-Seq) technology and found an array of …

The Development Of Azd7624 For Prevention Of Exacerbations In Copd: A Randomized Controlled Trial, Naimish R. Patel, Danen M. Cunoosamy, Malin Fagerås, Ziad Taib, Sara Asimus, Tove Hegelund-Myrbäck, Sofia Lundin, Katerina Pardali, Nisha Kurian, Eva Ersdal, Cecilia Kristensson, Katarina Korsback, Robert Palmér, Mary N. Brown, Steven Greenaway, Leonard Siew, Graham W. Clarke, Stephen I. Rennard, Barry J. Make, Robert A. Wise, Paul Jansson

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: p38 mitogen-activated protein kinase (MAPK) plays a central role in the regulation and activation of pro-inflammatory mediators. COPD patients have increased levels of activated p38 MAPK, which correlate with increased lung function impairment, alveolar wall inflammation, and COPD exacerbations.

OBJECTIVES: These studies aimed to assess the effect of p38 inhibition with AZD7624 in healthy volunteers and patients with COPD. The principal hypothesis was that decreasing lung inflammation via inhibition of p38α would reduce exacerbations and improve quality of life for COPD patients at high risk for acute exacerbations.

METHODS: The p38 isoform most relevant to lung inflammation was assessed …

Improved Therapy For Medulloblastoma: Targeting Hedgehog And Pi3k-Mtor Signaling Pathways In Combination With Chemotherapy, Nagendra K. Chaturvedi, Matthew J. Kling, Don W. Coulter, Timothy R. Mcguire, Sutapa Ray, Varun Kesherwani, Shantaram S. Joshi, J. Graham Sharp

Journal Articles: Radiation Oncology

Aberrant activation and interactions of hedgehog (HH) and PI3K/AKT/mTOR signaling pathways are frequently associated with high-risk medulloblastoma (MB). Thus, combined targeting of the HH and PI3K/AKT/mTOR pathways could be a viable therapeutic strategy to treat high-risk patients. Therefore, we investigated the anti-MB efficacies of combined HH inhibitor Vismodegib and PI3K-mTOR dual-inhibitor BEZ235 together or combined individually with cisplatin against high-risk MB. Using non-MYC- and MYC-amplified cell lines, and a xenograft mouse model, the in vitro and in vivo efficacies of these therapies on cell growth/survival and associated molecular mechanism(s) were investigated. Results showed that combined treatment of Vismodegib and BEZ235 …

Socioeconomic Status And Cigarette Expenditure Among Us Households: Results From 2010 To 2015 Consumer Expenditure Survey, Mohammad Siahpush, Evi A. Farazi, Shannon I. Maloney, Danae Dinkel, Minh N. Nguyen, Gopal K. Singh

Journal Articles: Epidemiology

OBJECTIVES: To examine (1) the association between household socioeconomic status (SES) and whether a household spends money on cigarettes and (2) socioeconomic variations in proportion of total household expenditure spent on cigarettes among smoking households.

METHODS: We pooled data from six consecutive years, 2010-2015, of the Consumer Expenditure Interview Survey. The interviews involved a structured questionnaire about household income, demographics and expenditures including expenditure on cigarettes. Households that reported cigarette expenditure in the previous 3 months were distinguished as smoking households. SES indicators were household poverty status, education and occupation of the head of household. Logistic regression was used to …

Catching Chances: The Movement To Be On The Ground And Research Ready Before An Outbreak, David Brett-Major, James V. Lawler

Journal Articles: Epidemiology

After more than 28,000 Ebola virus disease cases and at least 11,000 deaths in West Africa during the 2014⁻2016 epidemic, the world remains without a licensed vaccine or therapeutic broadly available and demonstrated to alleviate suffering. This deficiency has been felt acutely in the two, short, following years with two Ebola virus outbreaks in the Democratic Republic of Congo (DRC), and a Marburg virus outbreak in Uganda. Despite billions of U.S. dollars invested in developing medical countermeasures for filoviruses in the antecedent decades, resulting in an array of preventative, diagnostic, and therapeutic products, none are available on commercial shelves. This …

S-Nitrosation Of Protein Phosphatase 1 Mediates Alcohol-Induced Ciliary Dysfunction, Michael E. Price, Adam J. Case, Jacqueline A. Pavlik, Jane M. Devasure, Todd A. Wyatt, Matthew C. Zimmerman, Joseph H. Sisson

Journal Articles: Cellular & Integrative Physiology

Alcohol use disorder (AUD) is a strong risk factor for development and mortality of pneumonia. Mucociliary clearance, a key innate defense against pneumonia, is perturbed by alcohol use. Specifically, ciliated airway cells lose the ability to increase ciliary beat frequency (CBF) to β-agonist stimulation after prolonged alcohol exposure. We previously found that alcohol activates protein phosphatase 1 (PP1) through a redox mechanism to cause ciliary dysfunction. Therefore, we hypothesized that PP1 activity is enhanced by alcohol exposure through an S-nitrosothiol-dependent mechanism resulting in desensitization of CBF stimulation. Bronchoalveolar S-nitrosothiol (SNO) content and tracheal PP1 activity was increased in wild-type (WT) …

Xenosurveillance Reflects Traditional Sampling Techniques For The Identification Of Human Pathogens: A Comparative Study In West Africa, Joseph R. Fauver, James Weger-Lucarelli, Lawrence S. Fakoli, Kpehe Bolay, Fatorma K. Bolay, Joseph W. Diclaro, Doug E. Brackney, Brian D. Foy, Mark D. Stenglein, Gregory D. Ebel

Journal Articles: Epidemiology

BACKGROUND: Novel surveillance strategies are needed to detect the rapid and continuous emergence of infectious disease agents. Ideally, new sampling strategies should be simple to implement, technologically uncomplicated, and applicable to areas where emergence events are known to occur. To this end, xenosurveillance is a technique that makes use of blood collected by hematophagous arthropods to monitor and identify vertebrate pathogens. Mosquitoes are largely ubiquitous animals that often exist in sizable populations. As well, many domestic or peridomestic species of mosquitoes will preferentially take blood-meals from humans, making them a unique and largely untapped reservoir to collect human blood.

METHODOLOGY/PRINCIPAL …

Coming Out Of "Retirement"-Predictors Of Driving Resumption Among Older Drivers, Kendra Ratnapradipa, Jing Wang, Marla Berg-Weger, Mario Schootman

Journal Articles: Epidemiology

Background and Objectives: Predictors and consequences of driving cessation in older adults have been studied extensively. This study sought to establish the extent to which former drivers resume driving and identify associated factors.

Research Design and Methods: Descriptive analysis of the 2011-2015 National Health and Aging Trends Study data (Round 1:

Results: Among drivers who stopped driving during the study, 17%-28% resumed driving. Age, vehicle ownership, stroke, hospitalization, memory, and perceived transportation barriers were associated with resumption in regression analysis. In multilevel analysis stratified by baseline driving status, poor word recall (OR = 0.62; 95% CI = 0.40, 0.95) and …

Relationship Of Systemic Il-10 Levels With Proinflammatory Cytokine Responsiveness And Lung Function In Agriculture Workers, Tricia D. Levan, Debra J. Romberger, Mohammad Siahpush, Brandon L. Grimm, Athena K. Ramos, Patrik L. Johansson, Tzeyu L. Michaud, Art J. Heires, Todd A. Wyatt, Jill A. Poole

Journal Articles: Internal Medicine

BACKGROUND: Agriculture workers are exposed to microbial component- and particulate matter-enriched organic dust aerosols. Whereas it is clear that exposure to these aerosols can lead to lung inflammation, it is not known how inflammatory responses are resolved in some individuals while others develop chronic lung disease. Interleukin (IL)-10 is an immunomodulatory cytokine that is recognized as a potent anti-inflammatory and pro-resolving factor. The objective of this study was to determine whether there is a relationship of systemic IL-10 and proinflammatory responses and/or respiratory health effects in humans with prior agriculture exposure.

METHODS: This is a cross sectional study of 625 …