Medicine and Health Sciences Commons^™

Ovalbumin-Sensitized Mice Have Altered Airway Inflammation To Agriculture Organic Dust, Kristi J. Warren, John D. Dickinson, Amy J. Nelson, Todd A. Wyatt, Debra J. Romberger, Jill A. Poole

Journal Articles: Environmental, Agricultural & Occupational Health

Agriculture exposures are associated with reducing the risk of allergy and asthma in early life; yet, repeated exposures later in life are associated with chronic bronchitis and obstructive pulmonary diseases. The objective of this study was to investigate the airway inflammatory response to organic dust extract (ODE) in mice with established ovalbumin (OVA)-induced experimental asthma. C57BL/6 mice were either OVA sensitized/aerosol-exposed or saline (Sal) sensitized/aerosol-challenged. Both groups were then subsequently challenged once with intranasal saline or swine confinement ODE to obtain 4 treatment groups of Sal-Sal, Sal-ODE, OVA-Sal, and OVA-ODE. Airway hyper-responsiveness (AHR) to methacholine, bronchiolar lavage fluid, lung tissues, …

Consequences Of Pathogen Lists: Why Some Diseases May Continue To Plague Us, David Brett-Major, Trina Racine, Gary P. Kobinger

Journal Articles: Epidemiology

The current strategy used by many funding agencies for determining how money is spent on research to help prevent infectious disease outbreaks is based on pathogen-specific priority lists. Listing disease threats provides focus for business and research planning conducive to specific goals of developing a drug, or a vaccine, or other particular product. But, this singular type of focus has consequences. This perspective explores the consequences of lists, and describes how parallel programming independent of disease lists that address what we need to do to prevent and mitigate emerging disease risks may provide benefits out of reach of a singular …

Effect Of Abo Blood Group On Asymptomatic, Uncomplicated And Placental Plasmodium Falciparum Infection: Systematic Review And Meta-Analysis, Abraham Degarege, Merhawi T. Gebrezgi, Consuelo M. Beck-Sague, Mats Wahlgren, Luiz Carlos De Mattos, Purnima Madhivanan

Journal Articles: Epidemiology

BACKGROUND: Malaria clinical outcomes vary by erythrocyte characteristics, including ABO blood group, but the effect of ABO blood group on asymptomatic, uncomplicated and placental Plasmodium falciparum (P. falciparum) infection remains unclear. We explored effects of ABO blood group on asymptomatic, uncomplicated and placental falciparum infection in the published literature.

METHODS: A systematic review and meta-analysis was performed using the preferred reporting items for systematic reviews and meta-analyses guidelines. Articles in Pubmed, Embase, Web of Science, CINAHL and Cochrane Library published before February 04, 2017 were searched without restriction. Studies were included if they reported P. falciparum infection incidence or prevalence, …

The Impact Of Travel Time On Colorectal Cancer Stage At Diagnosis In A Privately Insured Population, Mesnad Alyabsi, Mary Charlton, Jane L. Meza, K. M. Monirul Islam, Amr Soliman, Shinobu Watanabe-Galloway

Journal Articles: Epidemiology

BACKGROUND: Rural residents are less likely to receive screening for colorectal cancer (CRC) than urban residents. However, the mechanisms underlying this disparity, especially among people aged 50-64 years old with private health insurance, are not well understood. We examined the impact of travel time on stage at CRC diagnosis.

METHODS: This retrospective cohort study used data from the Blue Cross and Blue Shield of Nebraska. Members of this private insurance company aged 50-64 years, diagnosed with CRC during the period 2012-2016, and continuously enrolled in the insurance plan for at least 6 months prior to CRC diagnosis, were selected for …

Vaccination Coverage And Awareness Of Hepatitis B Virus Among Healthcare Students At A University In Cyprus, Zoe Roupa, Maria Noula, Evi A. Farazi, Antonis Stylianides, Christos Papaneophytou

Journal Articles: Epidemiology

Introduction: The risk for healthcare students to get infected by transmitting infectious viruses, including hepatitis B virus (HBV), in a hospital setting is extremely high through exposure to blood and/or body secretions.

Aim: The aim of this work was to evaluate both the vaccination history of healthcare students at a University in Cyprus and their serologic immunity against HBV. In addition, we assessed their knowledge and behaviors towards the transmission and prevention of hepatitis B (HB).

Results: Total amount of 168 students participated in this study and more than 50% of them provided complete documentation of vaccination history against HBV. …

Awareness Of Human Papilloma Virus And Cervical Cancer Prevention Among Cypriot Female Healthcare Workers, Andria Christodoulou, Jirayr Ajzajian, Dejun Su, Hongmei Wang, Zoe Roupa, Evi A. Farazi

Journal Articles: Epidemiology

Background: Cervical cancer incidence varies around the world with the highest rates in Eastern Africa and the lowest rates in Western Asia. In Cyprus, a small Mediterranean island, cervical cancer incidence was 6.4 per 100,000 in 2013. HPV is an established risk factor for cervical cancer with HPV-16 and HPV-18 being the most common carcinogenic strains. Cervical cancer is preventable through primary (HPV vaccination) and secondary (Pap and HPV tests) prevention. These prevention methods should be promoted, however, in order to design a cancer prevention programme and the awareness and characteristics of populations should be investigated so that prevention programmes …

Reanalysis Of The Nccn Pd-L1 Companion Diagnostic Assay Study For Lung Cancer In The Context Of Pd-L1 Expression Findings In Triple-Negative Breast Cancer, David L. Rimm, Gang Han, Janis M. Taube, Eunhee S. Yi, Julia A. Bridge, Douglas B. Flieder, Robert Homer, Anja C. Roden, Fred R. Hirsch, Ignacio I. Wistuba, Lajos Pusztai

Journal Articles: Pathology and Microbiology

The companion diagnostic test for checkpoint inhibitor immune therapy is an immunohistochemical test for PD-L1. The test has been shown to be reproducible for expression in tumor cells, but not in immune cells. Immune cells were used in the IMpassion130 trial which showed PD-L1 expression was associated with a better outcome. Two large studies have been done assessing immune cell PD-L1 expression in lung cancer. Here, we reanalyze one of those studies, to show that, even with an easier scoring method, there is still only poor agreement between assays and pathologist for immune cell PD-L1 expression.

Observations Of Shear Stress Effects On Staphylococcus Aureus Biofilm Formation, Erica Sherman, Kenneth W. Bayles, Derek E. Moormeier, Jennifer L. Endres, Timothy Wei

Journal Articles: Pathology and Microbiology

Staphylococcus aureus bacteria form biofilms and distinctive microcolony or "tower" structures that facilitate their ability to tolerate antibiotic treatment and to spread within the human body. The formation of microcolonies, which break off, get carried downstream, and serve to initiate biofilms in other parts of the body, is of particular interest here. It is known that flow conditions play a role in the development, dispersion, and propagation of biofilms in general. The influence of flow on microcolony formation and, ultimately, what factors lead to microcolony development are, however, not well understood. The hypothesis being examined is that microcolony structures form …

Controlling Latent Tb Tuberculosis Infection In High-Burden Countries: A Neglected Strategy To End Tb, Gavin J. Churchyard, Susan Swindells

Journal Articles: Infectious Diseases

In a Perspective, Gavin Churchyard and Sue Swindells discuss the importance of strategies to target latent tuberculosis infection in high risk populations and thus disrupt a reservoir for new infections in high burden countries.

Urease Is An Essential Component Of The Acid Response Network Of Staphylococcus Aureus And Is Required For A Persistent Murine Kidney Infection, Chunyi Zhou, Fatema Bhinderwala, Mckenzie K. Lehman, Vinai Chittezham Thomas, Sujata S. Chaudhari, Kelsey J. Yamada, Kirk W. Foster, Robert Powers, Tammy Kielian, Paul D. Fey

Journal Articles: Pathology and Microbiology

Staphylococcus aureus causes acute and chronic infections resulting in significant morbidity. Urease, an enzyme that generates NH3 and CO2 from urea, is key to pH homeostasis in bacterial pathogens under acidic stress and nitrogen limitation. However, the function of urease in S. aureus niche colonization and nitrogen metabolism has not been extensively studied. We discovered that urease is essential for pH homeostasis and viability in urea-rich environments under weak acid stress. The regulation of urease transcription by CcpA, Agr, and CodY was identified in this study, implying a complex network that controls urease expression in response to changes in metabolic …

Tgf-Β Induces A Heart Failure Phenotype Via Fibroblasts Exosome Signaling, Hesham Basma, Adelaide N. Johanson, Kajari Dhar, Daniel R. Anderson, Fang Qiu, Stephen I. Rennard, Brian D. Lowes

Journal Articles: Pulmonary & Critical Care Med

PURPOSE: The mechanisms for persistent and progressive loss of myocardial function in advanced heart failure (HF) remain incompletely characterized. In the current study, we sought to determine the impact of TGF-β on fibroblasts transcriptional profiles and assess if exosomes from TGF-β treated fibroblasts could induce a heart failure phenotype in co-cultured cardiomyocytes.

METHOD: Normal heart fibroblasts were treated with TGF-β with a final conc. of 2.5 ng/ml in serum free media. HF fibroblasts were also obtained from patients undergoing implantation of left ventricular assist devices. Exosomes were collected using three-step ultracentrifugation. Cardiomyocytes were co-cultured with exosomes from TGF-β-treated, HF and …

Bronchoalveolar Lavage Fluid From Copd Patients Reveals More Compounds Associated With Disease Than Matched Plasma, Eitan Halper-Stromberg, Lucas Gillenwater, Charmion Cruickshank-Quinn, Wanda Kay O'Neal, Nichole Reisdorph, Irina Petrache, Yonghua Zhuang, Wassim W. Labaki, Jeffrey L. Curtis, James Wells, Stephen I. Rennard, Katherine A. Pratte, Prescott Woodruff, Kathleen A. Stringer, Katerina Kechris, Russell P. Bowler

Journal Articles: Pulmonary & Critical Care Med

Smoking causes chronic obstructive pulmonary disease (COPD). Though recent studies identified a COPD metabolomic signature in blood, no large studies examine the metabolome in bronchoalveolar lavage (BAL) fluid, a more direct representation of lung cell metabolism. We performed untargeted liquid chromatography-mass spectrometry (LC-MS) on BAL and matched plasma from 115 subjects from the SPIROMICS cohort. Regression was performed with COPD phenotypes as the outcome and metabolites as the predictor, adjusted for clinical covariates and false discovery rate. Weighted gene co-expression network analysis (WGCNA) grouped metabolites into modules which were then associated with phenotypes. K-means clustering grouped similar subjects. We detected …

It's More Than Low Bmi: Prevalence Of Cachexia And Associated Mortality In Copd, Merry-Lynn N. Mcdonald, Emiel F.M. Wouters, Erica Rutten, Richard Casaburi, Stephen I. Rennard, David A. Lomas, Marcas Bamman, Bartolome Celli, Alvar Agusti, Ruth Tal-Singer, Craig P. Hersh, Mark Dransfield, Edwin K. Silverman

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Cachexia is associated with increased mortality risk among chronic obstructive pulmonary disease (COPD) patients. However, low body mass index (BMI) as opposed to cachexia is often used, particularly when calculating the BODE (BMI, Obstruction, Dyspnea and Exercise) index. For this reason, we examined mortality using a consensus definition and a weight-loss definition of cachexia among COPD cases and compared two new COPD severity indices with BODE.

METHODS: In the current report, the consensus definition for cachexia incorporated weight-loss > 5% in 12-months or low BMI in addition to 3/5 of decreased muscle strength, fatigue, anorexia, low FFMI and inflammation. The …

Preprints In Dental Science: Dentrxiv As A Strategy To Bring Dental Research Into The Information Age, Jafar Kolahi, David G. Dunning, Edward F. Rossomando, Elham Bidram, Saber Khazaei

Journal Articles: College of Dentistry

No abstract provided.

Mapping Of Lymphatic Filariasis In Loiasis Areas: A New Strategy Shows No Evidence For Wuchereria Bancrofti Endemicity In Cameroon, Samuel Wanji, Mathias Eyong Esum, Abdel Jelil Njouendou, Amuam Andrew Mbeng, Patrick W Chounna Ndongmo, Raphael Awah Abong, Jerome Fru, Fanny F. Fombad, Gordon Takop Nchanji, Glory Ngongeh, Narcisse V. Ngandjui, Peter Ivo Enyong, Helen Storey, Kurt C. Curtis, Kerstin Fischer, Joseph R. Fauver, Daphne Lew, Charles W. Goss, Peter U. Fischer

Journal Articles: Epidemiology

BACKGROUND: Mapping of lymphatic filariasis (LF) caused by Wuchereria bancrofti largely relies on the detection of circulating antigen using ICT cards. Several studies have recently shown that this test can be cross-reactive with sera of subjects heavily infected with Loa loa and thus mapping results in loiasis endemic areas may be inaccurate.

METHODOLOGY/PRINCIPAL FINDINGS: In order to develop an LF mapping strategy for areas with high loiasis prevalence, we collected day blood samples from 5,001 subjects residing in 50 villages that make up 6 health districts throughout Cameroon. Antigen testing using Filarial Test Strip (FTS, a novel platform that uses …

Improving Socioeconomic Status May Reduce The Burden Of Malaria In Sub Saharan Africa: A Systematic Review And Meta-Analysis, Abraham Degarege, Kristopher Fennie, Dawit Degarege, Shasank Chennupati, Purnima Madhivanan

Journal Articles: Epidemiology

BACKGROUND: A clear understanding of the effects of housing structure, education, occupation, income, and wealth on malaria can help to better design socioeconomic interventions to control the disease. This literature review summarizes the relationship of housing structure, educational level, occupation, income, and wealth with the epidemiology of malaria in sub-Saharan Africa (SSA).

METHODS: A systematic review and meta-analysis was conducted following the preferred reporting items for systematic reviews and meta-analyses guidelines. The protocol for this study is registered in PROSPERO (ID=CRD42017056070), an international database of prospectively registered systematic reviews. On January 16, 2016, available literature was searched in PubMed, Embase, …

Insight Into The Dynamics Of Apobec3g Protein In Complexes With Dna Assessed By High Speed Afm, Yangang Pan, Luda S. Shlyakhtenko, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

APOBEC3G (A3G) is a single-stranded DNA (ssDNA) binding protein that restricts the HIV virus by deamination of dC to dU during reverse transcription of the viral genome. A3G has two zinc-binding domains: the N-terminal domain (NTD), which efficiently binds ssDNA, and the C-terminal catalytic domain (CTD), which supports deaminase activity of A3G. Until now, structural information on A3G has been lacking, preventing elucidation of the molecular mechanisms underlying its interaction with ssDNA and deaminase activity. We have recently built a computational model for the full-length A3G monomer and validated its structure using data obtained by time-lapse High-Speed Atomic Force Microscopy …

Human Islet Response To Selected Type 1 Diabetes-Associated Bacteria: A Transcriptome-Based Study, Ahmed M. Abdellatif, Heather Jensen Smith, Robert Z. Harms, Nora Sarvetnick

Journal Articles: Eppley Institute

Type 1 diabetes (T1D) is a chronic autoimmune disease that results from destruction of pancreatic β-cells. T1D subjects were recently shown to harbor distinct intestinal microbiome profiles. Based on these findings, the role of gut bacteria in T1D is being intensively investigated. The mechanism connecting intestinal microbial homeostasis with the development of T1D is unknown. Specific gut bacteria such as Bacteroides dorei (BD) and Ruminococcus gnavus (RG) show markedly increased abundance prior to the development of autoimmunity. One hypothesis is that these bacteria might traverse the damaged gut barrier, and their constituents elicit a response from human islets that causes …

Cash Transfers And Hiv/Hsv-2 Prevalence: A Replication Of A Cluster Randomized Trial In Malawi, Lynette M. Smith, Nicholas A. Hein, Danstan Bagenda

Journal Articles: Anesthesiology

INTRODUCTION: In this paper we perform a replication analysis of "Effect of a cash transfer programme for schooling on prevalence of HIV and herpes simplex type 2 in Malawi: a cluster randomised trial" by Sarah Baird and others published in "The Lancet" in 2012. The original study was a two-year cluster randomized intervention trial of never married girls aged 13-22 in Malawi. Enumeration areas were randomized to either an intervention involving cash transfer (conditional or unconditional of school enrollment) or control. The study included 1708 Malawian girls, who were enrolled at baseline and had biological testing for HIV and herpes …

Acceptability And Feasibility Of A Pharmacist-Led Hiv Pre-Exposure Prophylaxis (Prep) Program In The Midwestern United States, Joshua P. Havens, Kimberly Scarsi, Harlan Sayles, Donald G. Klepser, Susan Swindells, Sara H. Bares

Journal Articles: Infectious Diseases

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) substantially reduces the risk of HIV acquisition, yet significant barriers exist to its prescription and use. Incorporating pharmacists in the PrEP care process may help increase access to PrEP services.

METHODS: Our pharmacist-led PrEP program (P-PrEP) included pharmacists from a university-based HIV clinic, a community pharmacy, and two community-based clinics. Through a collaborative practice agreement, pharmacists conducted PrEP visits with potential candidates for PrEP, according to the recommended CDC guidelines, and authorized emtricitabine-tenofovir disoproxil fumarate prescriptions. Demographics and retention in care over 12 months were summarized and participant satisfaction and pharmacist acceptability with the P-PrEP …

Lipophagy And Alcohol-Induced Fatty Liver, Li Yang, Changqing Yang, Paul G. Thomes, Kusum K. Kharbanda, Carol A. Casey, Mark A. Mcniven, Terrence M. Donohue

Journal Articles: Internal Medicine

This review describes the influence of ethanol consumption on hepatic lipophagy, a selective form of autophagy during which fat-storing organelles known as lipid droplets (LDs) are degraded in lysosomes. During classical autophagy, also known as macroautophagy, all forms of macromolecules and organelles are sequestered in autophagosomes, which, with their cargo, fuse with lysosomes, forming autolysosomes in which the cargo is degraded. It is well established that excessive drinking accelerates intrahepatic lipid biosynthesis, enhances uptake of fatty acids by the liver from the plasma and impairs hepatic secretion of lipoproteins. All the latter contribute to alcohol-induced fatty liver (steatosis). Here, our …

Next-Generation Sequencing Of Hiv-1 Single Genome Amplicons, Gustavo H. Kijak, Eric Sanders-Buell, Phuc Pham, Elizabeth A. Harbolick, Celina Oropeza, Anne Marie O'Sullivan, Meera Bose, Charmagne G. Beckett, Mark Milazzo, Merlin L. Robb, Sheila A. Peel, Paul T. Scott, Nelson L. Michael, Adam W. Armstrong, Jerome H. Kim, David Brett-Major, Sodsai Tovanabutra

Journal Articles: Epidemiology

The analysis of HIV-1 sequences has helped understand the viral molecular epidemiology, monitor the development of antiretroviral drug resistance, and design candidate vaccines. The introduction of single genome amplification (SGA) has been a major advancement in the field, allowing for the characterization of multiple sequences per patient while preserving linkage among polymorphisms in the same viral genome copy. Sequencing of SGA amplicons is performed by capillary Sanger sequencing, which presents low throughput, requires a high amount of template, and is highly sensitive to template/primer mismatching. In order to meet the increasing demand for HIV-1 SGA amplicon sequencing, we have developed …

Using "Outbreak Science" To Strengthen The Use Of Models During Epidemics., Caitlin Rivers, Jean-Paul Chretien, Steven Riley, Julie A. Pavlin, Alexandra Woodward, David Brett-Major, Irina Maljkovic Berry, Lindsay Morton, Richard G. Jarman, Matthew Biggerstaff, Michael A. Johansson, Nicholas G. Reich, Diane Meyer, Michael R. Snyder, Simon Pollett

Journal Articles: Epidemiology

Infectious disease modeling has played a prominent role in recent outbreaks, yet integrating these analyses into public health decision-making has been challenging. We recommend establishing ‘outbreak science’ as an inter-disciplinary field to improve applied epidemic modeling.

New Filovirus Disease Classification And Nomenclature, Jens H. Kuhn, Takuya Adachi, Neill K.J. Adhikari, Jose R. Arribas, Ibrahima Elhadj Bah, Daniel G. Bausch, Nahid Bhadelia, Matthias Borchert, Arne Broch Brantsæter, David Brett-Major, Timothy H. Burgess, Daniel S. Chertow, Christopher G. Chute, Theodore J. Cieslak, Robert Colebunders, Ian Crozier, Richard T. Davey, Hilde De Clerck, Rafael Delgado, Laura Evans, Mosoka Fallah, William A. Fischer, Tom E. Fletcher, Robert A. Fowler, Thomas Grünewald, Andy Hall, Angela L. Hewlett, Andy I.M. Hoepelman, Catherine F. Houlihan, Giuseppe Ippolito, Shevin T. Jacob, Michael Jacobs, Robert Jakob, Frederique A. Jacquerioz, Laurent Kaiser, Andre C. Kalil, Rashidatu F. Kamara, Jimmy Kapetshi, Hans-Dieter Klenk, Gary Kobinger, Mark G. Kortepeter, Colleen S. Kraft, Thomas Kratz, Henry S. Kyobe Bosa, Marta Lado, François Lamontagne, H. Cliff Lane, Leslie Lobel, Julius Lutwama, G. Marshall Lyon, Moses B.F. Massaquoi, Thomas A. Massaquoi, Aneesh K. Mehta, Vital Mondonge Makuma, Srinivas Murthy, Tonny Seikikongo Musoke, Jean-Jacques Muyembe-Tamfum, Phiona Nakyeyune, Carolina Nanclares, Miriam Nanyunja, Justus Nsio-Mbeta, Tim O'Dempsey, Janusz T. Pawęska, Clarence J. Peters, Peter Piot, Christophe Rapp, Bertrand Renaud, Bruce Ribner, Pardis C. Sabeti, John S. Schieffelin, Werner Slenczka, Moses J. Soka, Armand Sprecher, James Strong, Robert Swanepoel, Timothy M. Uyeki, Michel Van Herp, Pauline Vetter, David A. Wohl, Timo Wolf, Anja Wolz, Alie H. Wurie, Zabulon Yoti

Journal Articles: Epidemiology

The recent large outbreak of Ebola virus disease (EVD) in Western Africa resulted in greatly increased accumulation of human genotypic, phenotypic and clinical data, and improved our understanding of the spectrum of clinical manifestations. As a result, the WHO disease classification of EVD underwent major revision.

De Novo Assembly Of The Brugia Malayi Genome Using Long Reads From A Single Minion Flowcell, Joseph R. Fauver, John Martin, Gary J. Weil, Makedonka Mitreva, Peter U. Fischer

Journal Articles: Epidemiology

Filarial nematode infections cause a substantial global disease burden. Genomic studies of filarial worms can improve our understanding of their biology and epidemiology. However, genomic information from field isolates is limited and available reference genomes are often discontinuous. Single molecule sequencing technologies can reduce the cost of genome sequencing and long reads produced from these devices can improve the contiguity and completeness of genome assemblies. In addition, these new technologies can make generation and analysis of large numbers of field isolates feasible. In this study, we assessed the performance of the Oxford Nanopore Technologies MinION for sequencing and assembling the …

Global Initiative Of The University Of Nebraska Medical Center To Improve Physical Therapy Education, Care And Science In China, Betsy J. Becker, Joseph F. Norman, Kyle Meyer, Ka-Chun Siu

Posters and Presentations: Physical Therapy

No abstract provided.

Individual- And County-Level Determinants Of High Breast Cancer Incidence Rates, Mario Schootman, Kendra Ratnapradipa, Travis Loux, Allese Mcvay, L. Joseph Su, Erik Nelson, Susan Kadlubar

Journal Articles: Epidemiology

Background: Age-adjusted breast cancer rates vary across and within states. However, most statistical models inherently identify either individual- or area-level determinants to explain geographic disparities in breast cancer rates and ignore the effects of the other level of determinants. We present a micro-macro modelling approach that incorporates both levels of determinants to better explain this variability and to discover opportunities to reduce breast cancer rates.

Methods: Individual-level data about breast cancer risk factors from eligible Arkansas Rural Community Health (ARCH) study participants (n=13,554) was supplemented with publicly available county-level data using a novel micro-macro statistical approach. This model uses individual-level …

A Synthetic Agonist To Vasoactive Intestinal Peptide Receptor-2 Induces Regulatory T Cell Neuroprotective Activities In Models Of Parkinson's Disease, R. Lee Mosley, Yaman Lu, Katherine E. Olson, Jatin Machhi, Wenhui Yan, Krista L. Namminga, Jenell R. Smith, Scott J. Shandler, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

A paradigm shift has emerged in Parkinson's disease (PD) highlighting the prominent role of CD4⁺ Tregs in pathogenesis and treatment. Bench to bedside research, conducted by others and our own laboratories, advanced a neuroprotective role for Tregs making pharmacologic transformation of immediate need. Herein, a vasoactive intestinal peptide receptor-2 (VIPR2) peptide agonist, LBT-3627, was developed as a neuroprotectant for PD-associated dopaminergic neurodegeneration. Employing both 6-hydroxydopamine (6-OHDA) and α-synuclein (α-Syn) overexpression models in rats, the sequential administration of LBT-3627 increased Treg activity without altering cell numbers both in naïve animals and during progressive nigrostriatal degeneration. LBT-3627 administration was linked to …

Autonomic And Redox Imbalance Correlates With T-Lymphocyte Inflammation In A Model Of Chronic Social Defeat Stress, Cassandra M. Moshfegh, Safwan K. Elkhatib, Christopher W. Collins, Allison J. Kohl, Adam J. Case

Journal Articles: Cellular & Integrative Physiology

Patients diagnosed with post-traumatic stress disorder (PTSD) are at a significantly elevated risk of developing comorbid inflammatory conditions, but the mechanisms underlying this predilection remain unclear. Our previous work has shown that T-lymphocytes exposed to elevated levels of norepinephrine (NE) displayed a pro-inflammatory signature reminiscent of an autoreactive phenotype. With this, we hypothesized that the increased sympathetic tone observed during psychological trauma may be promoting pro-inflammatory T-lymphocytes, which causes a predisposition to comorbid inflammatory conditions. Here, we examined the consequences of psychological trauma on splenic T-lymphocytes using a mouse model of repeated social defeat stress. Social defeat led to anxiety-like …

Afatinib And Temozolomide Combination Inhibits Tumorigenesis By Targeting Egfrviii-Cmet Signaling In Glioblastoma Cells, Raghupathy Vengoji, Muzafar A. Macha, Rama Krishna Nimmakayala, Satyanarayana Rachagani, Jawed A. Siddiqui, Kavita Mallya, Santhi Gorantla, Maneesh Jain, Moorthy P. Ponnusamy, Surinder K. Batra, Nicole Shonka

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Glioblastoma (GBM) is an aggressive brain tumor with universal recurrence and poor prognosis. The recurrence is largely driven by chemoradiation resistant cancer stem cells (CSCs). Epidermal growth factor receptor (EGFR) and its mutant EGFRvIII are amplified in ~ 60% and ~ 30% of GBM patients, respectively; however, therapies targeting EGFR have failed to improve disease outcome. EGFRvIII-mediated cross-activation of tyrosine kinase receptor, cMET, regulates GBM CSC maintenance and promote tumor recurrence. Here, we evaluated the efficacy of pan-EGFR inhibitor afatinib and Temozolomide (TMZ) combination on GBM in vitro and in vivo.

METHODS: We analyzed the effect of afatinib and …