Digital Commons Network^™

Seasonal Variations Of Complete Blood Count And Inflammatory Biomarkers In The Us Population - Analysis Of Nhanes Data, B. Liu, E. Taioli

Journal Articles

BACKGROUND: Recent studies reported seasonal differences in gene expression in white blood cells, adipose tissue, and inflammatory biomarkers of the immune system. There is no data on the seasonal variations of these biomarkers in the US general population of both children and adults. Then aim of this study is to explore the seasonal trends in complete blood count (CBC), and C-reactive protein (CRP) in a large non-institutionalized US population. METHODS: Seven cross-sectional data collected in the National Health and Nutrition Examination Survey (NHANES) during 1999-2012 were aggregated; participants reporting recent use of prescribed steroids, chemotherapy, immunomodulators and antibiotics were excluded. …

The Role Of B-1 Cells In Inflammation, M. Aziz, N. E. Holodick, T. L. Rothstein, P. Wang

Journal Articles

B-1 lymphocytes exhibit unique phenotypic, ontogenic, and functional characteristics that differ from the conventional B-2 cells. B-1 cells spontaneously secrete germline-like, repertoire-skewed polyreactive natural antibody, which acts as a first line of defense by neutralizing a wide range of pathogens before launching of the adaptive immune response. Immunomodulatory molecules such as interleukin-10, adenosine, granulocyte-macrophage colony-stimulating factor, interleukin-3, and interleukin-35 are also produced by B-1 cells in the presence or absence of stimulation, which regulate acute and chronic inflammatory diseases. Considerable progress has been made during the past three decades since the discovery of B-1 cells, which has improved not only …

Stimulation Of Brain Amp-Activated Protein Kinase Attenuates Inflammation And Acute Lung Injury In Sepsis, N. Mulchandani, W.L. Yang, M. M. Khan, F. Zhang, P. Marambaud, J. Nicastro, G.F. Coppa, P. Wang

Journal Articles

Sepsis and septic shock are enormous public health problems with astronomical financial repercussions on health systems worldwide. The central nervous system (CNS) is closely intertwined in the septic process but the underlying mechanism is still obscure. AMP-activated protein kinase (AMPK) is a ubiquitous energy sensor enzyme and plays a key role in regulation of energy homeostasis and cell survival. In this study, we hypothesized that activation of AMPK in the brain would attenuate inflammatory responses in sepsis, particularly in the lungs. Adult C57BL/6 male mice were treated with 5-aminoimidazole-4-carboxamide riboneucleotide (AICAR, 20 ng), an AMPK activator, or vehicle (normal saline) …

Differential Alterations Of Tissue T-Cell Subsets After Sepsis, A. Sharma, W.L. Yang, S. Matsuo, P. Wang

Journal Articles

Among immune cells in responding to sepsis, macrophages and neutrophils have been extensively studied, while the contribution of T lymphocytes and natural killer T (NKT) cells is less well characterized. Here we monitored tissue specific changes of T cell subsets in male C57BL/6 mice subjected to sham operation or cecal ligation and puncture (CLP) to induce polymicrobial sepsis. Thymus, spleen, liver, lungs and blood were processed and analyzed 20h later. Total lymphocyte count showed a significant reduction in septic thymus, spleen and blood but not in lungs and liver. The septic thymi were hypocellular with severe reduction in cell numbers …

Damp Signaling Is A Key Pathway Inducing Immune Modulation After Brain Injury, A. Liesz, A. Dalpke, E. Mracsko, D. J. Antoine, S. Roth, W. Zhou, H. Yang, P. P. Nawroth, K. J. Tracey, R. Veltkamp, +4 Additional Authors

Journal Articles

Acute brain lesions induce profound alterations of the peripheral immune response comprising the opposing phenomena of early immune activation and subsequent immunosuppression. The mechanisms underlying this brain-immune signaling are largely unknown. We used animal models for experimental brain ischemia as a paradigm of acute brain lesions and additionally investigated a large cohort of stroke patients. We analyzed release of HMGB1 isoforms by mass spectrometry and investigated its inflammatory potency and signaling pathways by immunological in vivo and in vitro techniques. Features of the complex behavioral sickness behavior syndrome were characterized by homecage behavior analysis. HMGB1 downstream signaling, particularly with RAGE, …

Age-Dependent Alterations In The Inflammatory Response To Pulmonary Challenge, H. M. Linge, K. Ochani, K. Lin, J. Y. Lee, E. J. Miller

Journal Articles

The aging lung is increasingly susceptible to infectious disease. Changes in pulmonary physiology and function are common in older populations, and in those older than 60 years, pneumonia is the major cause of infectious death. Understanding age-related changes in the innate and adaptive immune systems, and how they affect both pulmonary and systemic responses to pulmonary challenge are critical to the development of novel therapeutic strategies for the treatment of the elderly patient. In this observational study, we examined age-associated differences in inflammatory responses to pulmonary challenge with cell wall components from Gram-positive bacteria. Thus, male Sprague-Dawley rats, aged 6 …

Antibodies As Mediators Of Brain Pathology, L. Brimberg, S. Mader, Y. Fujieda, Y. Arinuma, C. Kowal, B. T. Volpe, B. Diamond

Journal Articles

No abstract provided.

The Brighter (And Evolutionarily Older) Face Of The Metabolic Syndrome: Evidence From Trypanosoma Cruzi Infection In Cd-1 Mice, W. Brima, D. J. Eden, S. F. Mehdi, M. Bravo, M. M. Wiese, J. Stein, V. Almonte, D. Zhao, J. Roth, F. Nagajyothi, +5 Additional Authors

Journal Articles

BACKGROUND: Infection with Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, results in chronic infection that leads to cardiomyopathy with increased mortality and morbidity in endemic regions. In a companion study, our group found that a high-fat diet (HFD) protected mice from T. cruzi-induced myocardial damage and significantly reduced post-infection mortality during acute T. cruzi infection. METHODS: In the present study metabolic syndrome was induced prior to T. cruzi infection by feeding a high fat diet. Also, mice were treated with anti-diabetic drug metformin. RESULTS: In the present study, the lethality of T. cruzi (Brazil strain) infection in CD-1 …

Malignancies, Particularly B-Cell Lymphomas, Are A Frequent Cause Of Mortality In Human Immunodeficiency Virus-1 Patients Despite Highly Active Antiretroviral Therapy, D. O. Griffin, M. Metzger, K. Poeth, K. Deng, A. Dharsee, J. C. Rico, J. Mcgowan

Journal Articles

Human immunodeficiency virus (HIV)-1-infected individuals are affected by diseases at rates above those of their HIV-negative peers despite the increased life expectancy of the highly active antiretroviral therapy era. We followed a cohort of approximately 2000 HIV-1-infected patients for 5 years. The most frequent cause of death in this HIV-1-infected cohort was malignancy, with 39% of all classified deaths due to cancer. Among the cancer deaths, B-cell lymphomas were the most commonly seen malignancy, representing 34% of all cancer deaths. These lymphomas were very aggressive with a median survival ofdiagnosis.

Fungal Infections In Renal Transplant Patients, A. Khan, E. El-Charabaty, S. El-Sayegh

Journal Articles

Organ transplantation has always been considered to be the standard therapeutic interventions in patients with end-stage organ failure. In 2008, more than 29,000 organ transplants were performed in US. Survival rates among transplant recipients have greatly improved due to better understanding of transplant biology and more effective immunosuppressive agents. After transplant, the extent of the immune response is influenced by the amount of interleukin 2 (IL-2) being produced by the T-helper cells. Transplant immunosuppressive therapy primarily targets T cell-mediated graft rejection. Calcineurin inhibitor, which includes cyclosporine, pimecrolimus and tacrolimus, impairs calcineurin-induced up-regulation of IL-2 expression, resulting in increased susceptibility to …

Augmenting Nf-Kappab In Poor-Risk Cll: A General Paradigm For Other Cancers?, D. Tuveson, K. R. Rai

Journal Articles

No abstract provided.

Md-2 Is Required For Disulfide Hmgb1-Dependent Tlr4 Signaling, H. Yang, H. Wang, Z. Ju, A. A. Ragab, W. Long, S. I. Valdes-Ferrer, M. He, J. Li, B. Lu, J. Roth, S. S. Chavan, K. J. Tracey, Y. Al-Abed, +10 Additional Authors

Journal Articles

Innate immune receptors for pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) orchestrate inflammatory responses to infection and injury. Secreted by activated immune cells or passively released by damaged cells, HMGB1 is subjected to redox modification that distinctly influences its extracellular functions. Previously, it was unknown how the TLR4 signalosome distinguished between HMGB1 isoforms. Here we demonstrate that the extracellular TLR4 adaptor, myeloid differentiation factor 2 (MD-2), binds specifically to the cytokine-inducing disulfide isoform of HMGB1, to the exclusion of other isoforms. Using MD-2-deficient mice, as well as MD-2 silencing in macrophages, we show a requirement for HMGB1-dependent TLR4 signaling. …

Modular Analysis Of Peripheral Blood Gene Expression In Rheumatoid Arthritis Captures Reproducible Gene Expression Changes In Tumor Necrosis Factor Responders, M. Oswald, M. E. Curran, S. L. Lamberth, R. M. Townsend, J. D. Hamilton, D. N. Chernoff, M. Kern, C. M. Pond, A. Lee, P. K. Gregersen, +3 Additional Authors

Journal Articles

Objective. To establish whether the analysis of whole-blood gene expression is useful in predicting or monitoring response to anti-tumor necrosis factor (anti-TNF) therapy in patients with rheumatoid arthritis (RA). Methods. Whole-blood RNA (using a PAXgene system to stabilize whole-blood RNA in the collection tube) was obtained at baseline and at 14 weeks from 3 independent cohorts, consisting of a combined total of 240 RA patients who were beginning therapy with anti-TNF. We used an approach to gene expression analysis that is based on modular patterns of gene expression, or modules. Results. Good and moderate responders according to the European League …

Randomized, Double-Blind, Placebo-Controlled Trial Of The Effect Of Vitamin D3 On The Interferon Signature In Patients With Systemic Lupus Erythematosus, C. Aranow, D. L. Kamen, M. Dall'era, E. M. Massarotti, M. C. Mackay, F. Koumpouras, A. Coca, W. W. Chatham, M. E. Clowse, L. G. Criscione-Schreiber, S. Callahan, E. A. Goldmuntz, L. Keyes-Elstein, M. Oswald, P. K. Gregersen, B. Diamond

Journal Articles

OBJECTIVE: Vitamin D modulates the immune response and blocks induction of an interferon (IFN) signature by systemic lupus erythematosus (SLE) sera. This study was undertaken to investigate the effects of vitamin D supplementation on the IFN signature in patients with SLE. METHODS: SLE patients (n = 57) with stable, inactive disease, a serum 25-hydroxyvitamin D (25[OH]D) level/=30 ng/ml) was not observed in any of the patients who were receiving placebo, while repletion was observed in 16 of 33 patients receiving vitamin D3 . The percentage of patients with an IFN signature response did not differ among the treatment groups. Moreover, …

The Macrophage Inhibitor Cni-1493 Blocks Metastasis In A Mouse Model Of Ewing Sarcoma Through Inhibition Of Extravasation, A. J. Hesketh, C. Maloney, C. A. Behr, M. C. Edelman, R. D. Glick, Y. Al-Abed, M. Symons, S. Z. Soffer, B. M. Steinberg

Journal Articles

Metastatic Ewing Sarcoma carries a poor prognosis, and novel therapeutics to prevent and treat metastatic disease are greatly needed. Recent evidence demonstrates that tumor-associated macrophages in Ewing Sarcoma are associated with more advanced disease. While some macrophage phenotypes (M1) exhibit anti-tumor activity, distinct phenotypes (M2) may contribute to malignant progression and metastasis. In this study, we show that M2 macrophages promote Ewing Sarcoma invasion and extravasation, pointing to a potential target of anti-metastatic therapy. CNI-1493 is a selective inhibitor of macrophage function and has shown to be safe in clinical trials as an anti-inflammatory agent. In a xenograft mouse model …

Assessment Of Reproducibility Of Matrix-Assisted Laser Desorption Ionization-Time Of Flight Mass Spectrometry For Bacterial And Yeast Identification, L. F. Westblade, O. B. Garner, D. H. Pincus, A. B. Mochon, R. Jennemann, R. Manji, M. Bythrow, M. A. Lewinski, C. A. D. Burnham, C. C. Ginocchio, +2 Additional Authors

Journal Articles

Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) has revolutionized the identification of clinical bacterial and yeast isolates. However, data describing the reproducibility of MALDI-TOF MS for microbial identification are scarce. In this study, we show that MALDI-TOF MS-based microbial identification is highly reproducible and can tolerate numerous variables, including differences in testing environments, instruments, operators, reagent lots, and sample positioning patterns. Finally, we reveal that samples of bacterial and yeast isolates prepared for MALDI-TOF MS identification can be repeatedly analyzed without compromising organism identification.

"The Great Mimicker": An Unusual Etiology Of Cytopenia, Diffuse Lymphadenopathy, And Massive Splenomegaly, M. Zaarour, C. Weerasinghe, E. Moussaly, S. Hussein, J. P. Atallah

Journal Articles

Sarcoidosis is an idiopathic multisystem disease characterized by the formation of noncaseating granulomas. It frequently presents with pulmonary infiltrates and bilateral hilar and mediastinal lymphadenopathy. Splenic involvement is common, but massive splenomegaly is a rare occurrence. Sarcoidosis is known as "the great mimicker" (or "the great imitator") since it exhibits a myriad of symptoms, mimicking other inflammatory, infectious, and neoplastic conditions, including lymphoma. Herein, we report the case of a 44-year-old male patient who was found to have bicytopenia, hypercalcemia, diffuse lymphadenopathy, and massive splenomegaly, a constellation of findings suggestive of underlying lymphoma. Interestingly, lymph node biopsy showed noncaseating granulomas …

Successful Treatment Of Peritoneal Dialysis Catheter-Related Polymicrobial Peritonitis Involving Clostridium Difficile, A Case Report And Review Of The Literature, S. Bharti, P. Malhotra, S. Juretschko

Journal Articles

Clostridium difficile is one of the most common nosocomial pathogens and the cause of pseudomembranous colitis in cases of prior antimicrobial exposure. Extra intestinal manifestations of C. difficile are uncommon and rarely reported. We report the first successfully treated case of catheter-related C. difficile peritonitis in a patient undergoing peritoneal dialysis.

Detecting Signals Of Seasonal Influenza Severity Through Age Dynamics, Elizabeth C Lee, Cécile Viboud, Lone Simonsen, Farid Khan, Shweta Bansal

Global Health Faculty Publications

BACKGROUND: Measures of population-level influenza severity are important for public health planning, but estimates are often based on case-fatality and case-hospitalization risks, which require multiple data sources, are prone to surveillance biases, and are typically unavailable in the early stages of an outbreak. To address the limitations of traditional indicators, we propose a novel severity index based on influenza age dynamics estimated from routine physician diagnosis data that can be used retrospectively and for early warning.

METHODS: We developed a quantitative 'ground truth' severity benchmark that synthesizes multiple traditional severity indicators from publicly available influenza surveillance data in the United …

Town Of Derry Annual Report Fiscal Year Ending June 30, 2015., Derry Town Representatives

Derry, NH Annual Reports

This is an annual report containing vital statistics for a town/city in the state of New Hampshire.

The Inclusion Of Women’S Health In Sustainable Medical Mission Trip Models: A Pa Student’S Perspective, Jillian G. Goles

VA Engage Journal

Like many disadvantaged countries around the world, Nicaragua is visited by numerous medical missions each year. The efficacy of these missions relies on the organization’s relationship with the communities they serve. Although the general goal of all medical missions is to ultimately help underserved populations, many missions inadvertently do harm. Two critical causes of such inadvertent harm are lack of sustainable practices and failure to form a long-term relationship with the communities. Shenandoah University’s Physician Assistant Program has worked tirelessly to form an ideal medical mission model and relationship with El Ayudante, a local non-government humanitarian organization, and the local …

Assessing Students' Acquisition Of Scientific Reasoning In An Experimental Psychology Class, Gayle S. Morse, Donald F. Graves, Kerry K. Prout, Jennifer Safford

Pedagogy and the Human Sciences

This pilot study is an initial exploration of a theoretical rubric proposed to "describe the progress of students’ acquisition of scientific inquiry" (Halonen et al., 2003, p. 196), and an application of the utility of the rubric. Twenty-two undergraduates from a woman’s college participated in two sections of experimental psychology. Students consisted of sophomores, juniors, and seniors who completed general psychology courses. Consistent with the Halonen et al. (2003) model, results indicated that authentic research experiences in the first phase of the course were positively correlated with changes in scientific thinking in a second phase. In turn, experiences in the …

Time For T? Immunoinformatics Addresses The Challenges Of Vaccine Design For Neglected Tropical And Emerging Infectious Diseases, Francis E. Terry, Leonard Moise, Rebecca Martin, Melissa Torres, Nils Pilotte, Steven Williams, Anne S. De Groot

Institute for Immunology and Informatics Faculty Publications

Vaccines have been invaluable for global health, saving lives and reducing healthcare costs, while also raising the quality of human life. However, newly emerging infectious diseases (EID) and more well-established tropical disease pathogens present complex challenges to vaccine developers; in particular, neglected tropical diseases, which are most prevalent among the world’s poorest, include many pathogens with large sizes, multistage life cycles and a variety of nonhuman vectors. EID such as MERS-CoV and H7N9 are highly pathogenic for humans. For many of these pathogens, while their genomes are available, immune correlates of protection are currently unknown. These complexities make developing vaccines …

Research At The University Of Nebraska-Lincoln: 2014-2015 Report, Vicki Miller, Ashley Washburn, Monica Norby, Elizabeth Banset, Gillian Klucas

Office of Research and Economic Development: Publications

The 2014-2015 UNL Research Report, published by the University of Nebraska-Lincoln Office of Research and Economic Development, highlights some of the diverse research, scholarship and creative activity at the heart of UNL’s research enterprise. A companion website includes more photos, videos and additional resources.

Creutzfeldt-Jakob Disease And Alzheimer’S Disease: Does Overlap Of Mechanism Mean Overlap Of Treatment Methods?, David Rotblat

The Science Journal of the Lander College of Arts and Sciences

Alzheimer’s disease is a neurodegenerative disorder that is the 6th leading cause of death in the United States. More than 5.5 million People over the age of 65 are currently diagnosed with Alzheimer’s disease with predictions of 13.8 million to be diagnosed by the year 2050 (Sultana, et al., 2013) (Hebert, Weuve, Scherr, & Evans, 2013). With few treatments available, scientists are desperately looking for a solution to this growing epidemic. Creutzfeldt-Jakob disease is also a neurodegenerative disorder, but with a far less prevalence of only 4.6 persons per million per year. It was discovered that Alzheimer’s and Creutzfeldt-Jakob disease …

Macalester Today Winter 2015, Macalester College

Macalester Today

No abstract provided.

Momentum: Research & Innovation For Winter 2015, University Of Rhode Island

Publications (Research and Economic Development)

The Winter 2015 issue of Momentum: Research & Innovation, a periodical focused on research at the University of Rhode Island.

Psychiatric Genome-Wide Association Study Analyses Implicate Neuronal, Immune And Histone Pathways, C. O'Dushlaine, C. Betancur, S. Herms, R. Krasucki, M. Leboyer, D. H. Ledbetter, T. Lencz, A. K. Malhotra, J. W. Smoller, P. A. Holmans, +365 Additional Authors

Journal Articles

Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple …

Use Of Serogroup B Meningococcal Vaccines In Adolescents And Young Adults: Recommendations Of The Advisory Committee On Immunization Practices, 2015, J. R. Macneil, L. Rubin, T. Folaranmi, I. R. Ortega-Sanchez, M. Patel, S. W. Martin

Journal Articles

At its June 2015 meeting, the Advisory Committee on Immunization Practices (ACIP) recommended that adolescents and young adults aged 16-23 years may be vaccinated with a serogroup B meningococcal (MenB) vaccine to provide short-term protection against most strains of serogroup B meningococcal disease. This report summarizes the deliberations of ACIP, the rationale for its decision, and recommendations for use of MenB vaccines in adolescents and young adults. Two MenB vaccines have recently been licensed by the Food and Drug Administration (FDA) for use in the United States and approved for use in persons aged 10-25 years: MenB-FHbp (Trumenba, Wyeth Pharmaceuticals, …

Neutralizing Antibodies Against West Nile Virus Identified Directly From Human B Cells By Single-Cell Analysis And Next Generation Sequencing, K. Tsioris, N. T. Gupta, A. O. Ogunniyi, R. M. Zimnisky, F. Qian, Y. Yao, X. Wang, J. N. Stern, R. Chari, J. C. Love, +8 Additional Authors

Journal Articles

West Nile virus (WNV) infection is an emerging mosquito-borne disease that can lead to severe neurological illness and currently has no available treatment or vaccine. Using microengraving, an integrated single-cell analysis method, we analyzed a cohort of subjects infected with WNV - recently infected and post-convalescent subjects - and efficiently identified four novel WNV neutralizing antibodies. We also assessed the humoral response to WNV on a single-cell and repertoire level by integrating next generation sequencing (NGS) into our analysis. The results from single-cell analysis indicate persistence of WNV-specific memory B cells and antibody-secreting cells in post-convalescent subjects. These cells exhibited …