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Full-Text Articles in Medicine and Health Sciences

Does The Microbiota Play A Role In The Pathogenesis Of Autoimmune Diseases?, Mairi H. Mclean, Dario Dieguez, Lindsey M. Miller, Howard A. Young Aug 2015

Does The Microbiota Play A Role In The Pathogenesis Of Autoimmune Diseases?, Mairi H. Mclean, Dario Dieguez, Lindsey M. Miller, Howard A. Young

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The microbiota of the human metaorganism is not a mere bystander. These microbes have coevolved with us and are pivotal to normal development and homoeostasis. Dysbiosis of the GI microbiota is associated with many disease susceptibilities, including obesity, malignancy, liver disease and GI pathology such as IBD. It is clear that there is direct and indirect crosstalk between this microbial community and host immune response. However, the precise mechanism of this microbial influence in disease pathogenesis remains elusive and is now a major research focus. There is emerging literature on the role of the microbiota in the pathogenesis of autoimmune …


Nos Inhibition Modulates Immune Polarization And Improves Radiation-Induced Tumor Growth Delay, Lisa A. Ridnour, Robert Y.S. Cheng, Jonathan M. Weiss, Sukhbir Kaur, David R. Soto-Pantoja, Debashree Basudhar, Julie L. Heinecke, C. Andrew Stewart, William Degraff, Anastasia L. Sowers, Angela Thetford, Aparna H. Kesarwala, David D. Roberts, Howard A. Young, James B. Mitchell, Giorgio Trinchieri, Robert H. Wiltrout, David A. Wink Jul 2015

Nos Inhibition Modulates Immune Polarization And Improves Radiation-Induced Tumor Growth Delay, Lisa A. Ridnour, Robert Y.S. Cheng, Jonathan M. Weiss, Sukhbir Kaur, David R. Soto-Pantoja, Debashree Basudhar, Julie L. Heinecke, C. Andrew Stewart, William Degraff, Anastasia L. Sowers, Angela Thetford, Aparna H. Kesarwala, David D. Roberts, Howard A. Young, James B. Mitchell, Giorgio Trinchieri, Robert H. Wiltrout, David A. Wink

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Nitric oxide synthases (NOS) are important mediators of progrowth signaling in tumor cells, as they regulate angiogenesis, immune response, and immune-mediated wound healing. Ionizing radiation (IR) is also an immune modulator and inducer of wound response. We hypothesized that radiation therapeutic efficacy could be improved by targeting NOS following tumor irradiation. Herein, we show enhanced radiation-induced (10 Gy) tumor growth delay in a syngeneic model (C3H) but not immunosuppressed (Nu/Nu) squamous cell carcinoma tumor-bearing mice treated post-IR with the constitutive NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME). These results suggest a requirement of T cells for improved radiation tumor response. In …


Sera From Patients With Active Systemic Lupus Erythematosus Patients Enhance The Toll-Like Receptor 4 Response In Monocyte Subsets, Tiago Carvalheiro, Diane Gomes, Ligia A. Pinto, Luis Inês, Ana Lopes, Ana Henriques, Susana Pedreiro, António Martinho, Hélder Trindade, Howard A. Young, José António Pereira Da Silva, Artur Paiva May 2015

Sera From Patients With Active Systemic Lupus Erythematosus Patients Enhance The Toll-Like Receptor 4 Response In Monocyte Subsets, Tiago Carvalheiro, Diane Gomes, Ligia A. Pinto, Luis Inês, Ana Lopes, Ana Henriques, Susana Pedreiro, António Martinho, Hélder Trindade, Howard A. Young, José António Pereira Da Silva, Artur Paiva

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Background: Systemic Lupus Erythematosus (SLE) is an auto-immune disease whose complex pathogenesis remains unraveled. Here we aim to explore the inflammatory ability of SLE patients' sera upon peripheral blood (PB) monocyte subsets and myeloid dendritic cells (mDCs) obtained from healthy donors. Methods: In this study we included 11 SLE patients with active disease (ASLE), 11 with inactive disease (ISLE) and 10 healthy controls (HC). PB from healthy donors was stimulated with patients' sera, toll-like receptor (TLR) 4 ligand - lipopolysaccharide or both. The intracellular production of TNF-α was evaluated in classical, non-classical monocytes and mDCs, using flow cytometry. TNF-α mRNA …


Short Course In The Microbiome, Kimberly Falana, Rob Knight, Camilia R. Martin, Romina Goldszmid, K. Leigh Greathouse, Joanne Gere, Howard Young, Winston Patrick Kuo Jan 2015

Short Course In The Microbiome, Kimberly Falana, Rob Knight, Camilia R. Martin, Romina Goldszmid, K. Leigh Greathouse, Joanne Gere, Howard Young, Winston Patrick Kuo

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Over the past decade, it has become evident that the microbiome is an important environmental factor that affects many physiological processes, such as cell proliferation and differentiation, behaviour, immune function and metabolism. More importantly, it may contribute to a wide variety of diseases, including cancer, inflammatory diseases, metabolic diseases and responses to pathogens. We expect that international, integrative and interdisciplinary translational research teams, along with the emergence of FDA-approved platforms, will set the framework for microbiome-based therapeutics and diagnostics. We recognize that the microbiome ecosystem offers new promise for personalized/precision medicine and targeted treatment for a variety of diseases. The …


Ifn-Γ Causes Aplastic Anemia By Altering Hematopoietic Stem/Progenitor Cell Composition And Disrupting Lineage Differentiation, Fan Ching Lin, Megan Karwan, Bahara Saleh, Deborah L. Hodge, Tim Chan, Kimberly C. Boelte, Jonathan R. Keller, Howard A. Young Dec 2014

Ifn-Γ Causes Aplastic Anemia By Altering Hematopoietic Stem/Progenitor Cell Composition And Disrupting Lineage Differentiation, Fan Ching Lin, Megan Karwan, Bahara Saleh, Deborah L. Hodge, Tim Chan, Kimberly C. Boelte, Jonathan R. Keller, Howard A. Young

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Aplastic anemia (AA) is characterized by hypocellular marrow and peripheral pancytopenia. Because interferon gamma (IFN-γ) can be detected in peripheral blood mononuclear cells of AA patients, it has been hypothesized that autoreactive T lymphocytes may be involved in destroying the hematopoietic stem cells. We have observed AA-like symptoms in our IFN-γ adenylate-uridylate-rich element (ARE)-deleted (del) mice, which constitutively express a low level of IFN-γ under normal physiologic conditions. Because no T-cell autoimmunity was observed, we hypothesized that IFN-γ may be directly involved in the pathophysiology of AA. In these mice, we did not detect infiltration of T cells in bone …


Ifn-Gamma Au-Rich Element Removal Promotes Chronic Ifn-Gamma Expression And Autoimmunity In Mice, Deborah L. Hodge, Cyril Berthet, Vincenzo Coppola, Wolfgang Kastenmüller, Matthew D. Buschman, Paul M. Schaughency, Hidekazu Shirota, Anthony J. Scarzello, Jeff J. Subleski, Miriam R. Anver, John R. Ortaldo, Fanching Lin, Della A. Reynolds, Michael E. Sanford, Philipp Kaldis, Lino Tessarollo, Dennis M. Klinman, Howard A. Young Sep 2014

Ifn-Gamma Au-Rich Element Removal Promotes Chronic Ifn-Gamma Expression And Autoimmunity In Mice, Deborah L. Hodge, Cyril Berthet, Vincenzo Coppola, Wolfgang Kastenmüller, Matthew D. Buschman, Paul M. Schaughency, Hidekazu Shirota, Anthony J. Scarzello, Jeff J. Subleski, Miriam R. Anver, John R. Ortaldo, Fanching Lin, Della A. Reynolds, Michael E. Sanford, Philipp Kaldis, Lino Tessarollo, Dennis M. Klinman, Howard A. Young

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We generated a mouse model with a 162 nt AU-rich element (ARE) region deletion in the 3' untranslated region (3'UTR) of the interferon-gamma (IFN-γ) gene that results in chronic circulating serum IFN-γ levels. Mice homozygous for the ARE deletion (ARE-Del) (-/-) present both serologic and cellular abnormalities typical of patients with systemic lupus erythematosus (SLE). ARE-Del(-/-) mice display increased numbers of pDCs in bone marrow and spleen. Addition of IFN-γ to Flt3-ligand (Flt3L) treated in vitro bone marrow cultures results in a 2-fold increase in pDCs with concurrent increases in IRF8 expression. Marginal zone B (MZB) cells and marginal zone …


Interferons: Success In Anti-Viral Immunotherapy, Fan Ching Lin, Howard A. Young Aug 2014

Interferons: Success In Anti-Viral Immunotherapy, Fan Ching Lin, Howard A. Young

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The interferons (IFNs) are glycoproteins with strong antiviral activities that represent one of the first lines of host defense against invading pathogens. These proteins are classified into three groups, Type I, II and III IFNs, based on the structure of their receptors on the cell surface. Due to their ability to modulate immune responses, they have become attractive therapeutic options to control chronic virus infections. In combination with other drugs, Type I IFNs are considered as "standard of care" in suppressing Hepatitis C (HCV) and Hepatitis B (HBV) infections, while Type III IFN has generated encouraging results as a treatment …


Tumor Microenvironment-Based Feed-Forward Regulation Of Nos2 In Breast Cancer Progression, Julie L. Heinecke, Lisa A. Ridnour, Robert Y.S. Cheng, Christopher H. Switzer, Michael M. Lizardo, Chand Khanna, Sharon A. Glynn, S. Perwez Hussain, Howard A. Young, Stefan Ambs, David A. Wink Apr 2014

Tumor Microenvironment-Based Feed-Forward Regulation Of Nos2 In Breast Cancer Progression, Julie L. Heinecke, Lisa A. Ridnour, Robert Y.S. Cheng, Christopher H. Switzer, Michael M. Lizardo, Chand Khanna, Sharon A. Glynn, S. Perwez Hussain, Howard A. Young, Stefan Ambs, David A. Wink

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Inflammation is widely recognized as an inducer of cancer progression. The inflammation-associated enzyme, inducible nitric oxide synthase (NOS2), has emerged as a candidate oncogene in estrogen receptor (ER)-negative breast cancer, and its increased expression is associated with disease aggressiveness and poor survival. Although these observations implicate NOS2 as an attractive therapeutic target, the mechanisms of both NOS2 induction in tumors and nitric oxide (NO)-driven cancer progression are not fully understood. To enhance ourmechanistic understanding of NOS2 induction in tumors and its role in tumor biology, we used stimulants of NOS2 expression in ER- and ER+ breast cancer cells and examined …


The Burden Of Influenza-Like Illness In The Us Workforce, Y. Tsai, F. Zhou, I. K. Kim Mar 2014

The Burden Of Influenza-Like Illness In The Us Workforce, Y. Tsai, F. Zhou, I. K. Kim

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Background -- The disease burden of influenza-like illnesses (ILIs) on the working population has been documented in the literature, but statistical evidence of ILI-related work absenteeism in the USA is limited due to data availability.

Aims -- To assess work absenteeism due to ILIs among privately insured employees in the USA in 2007–8 and 2008–9.

Methods -- We used the 2007–9 MarketScan® research databases. Full-time employees aged 18–64 years, with the ability to incur work absence and continuously enroled in the same insurance plan during each season were included. We identified ILI episodes using ICD-9 codes for influenza and …


Abrogation Of Tnfα Production During Cancer Immunotherapy Is Crucial For Suppressing Side Effects Due To The Systemic Expression Of Il-12, Bibiana Barrios, Natalia S. Baez, Della Reynolds, Pablo Iribarren, Hugo Cejas, Howard A. Young, Maria Cecilia Rodriguez-Galan Feb 2014

Abrogation Of Tnfα Production During Cancer Immunotherapy Is Crucial For Suppressing Side Effects Due To The Systemic Expression Of Il-12, Bibiana Barrios, Natalia S. Baez, Della Reynolds, Pablo Iribarren, Hugo Cejas, Howard A. Young, Maria Cecilia Rodriguez-Galan

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For more than a decade, the cytokine interleukin-12 (IL-12) has been utilized, either alone or in combination with other drugs, as a treatment for cancer. The numerous anti-tumor properties of IL-12 still generate interest in the clinical use of this cytokine, even though it has demonstrated toxicity when administrated systemically. As an approach to overcome this toxicity, numerous laboratories have attempted to induce IL-12 expression at the site of the tumor. However for tumors that are difficult to remove surgically or for the treatment of disseminated metastases, systemic expression of this cytokine still remains as the most efficient method of …


Impaired Hcv Clearance In Hiv/Hcv Coinfected Subjects Treated With Pegifn And Rbv Due To Interference Of Ifn Signaling By Ifnαr2a, Yu Jin Lee, Xiaozhen Zhang, Estefania Vazquez, Gayathri Shivasabesan, Howard A. Young, Alison Murphy, Honghui Wang, Anthony F. Suffredini, Ulrich Siebenlist, Shyam Kottilil Jan 2014

Impaired Hcv Clearance In Hiv/Hcv Coinfected Subjects Treated With Pegifn And Rbv Due To Interference Of Ifn Signaling By Ifnαr2a, Yu Jin Lee, Xiaozhen Zhang, Estefania Vazquez, Gayathri Shivasabesan, Howard A. Young, Alison Murphy, Honghui Wang, Anthony F. Suffredini, Ulrich Siebenlist, Shyam Kottilil

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Enhanced endogenous interferon (IFN) stimulated gene (ISG) signature has been associated with nonresponsiveness to hepatitis C treatment using pegylated-IFNα (pegIFNα) and ribavirin (RBV) in human immunodeficiency virus/hepatitis C virus (HIV/HCV) coinfected patients. Using a proteomic approach, we identified high levels of IFNα receptor 2a (IFNαR2a) in the serum of null responders to pegIFNα/RBV. IFNαR2a inhibited antiviral activity of all formulations of IFNα in JFH/Huh7.5 cells. Furthermore, serum from null responders, but not from those who achieved sustained virologic response, suppressed IFN-signaling and ISG expression in IFNα-stimulated PBMCs of healthy donors in an IFNαR2a specific fashion. An IFNαR2a transgenic mice model …


All-Cause Gastroenteritis And Rotavirus-Coded Hospitalizations Among Us Children, 2000–2009, Rishi Desai, Aaron T. Curns, Claudia A. Steiner, Jacqueline E. Tate, Manish M. Patel, Umesh D. Parashar Jun 2012

All-Cause Gastroenteritis And Rotavirus-Coded Hospitalizations Among Us Children, 2000–2009, Rishi Desai, Aaron T. Curns, Claudia A. Steiner, Jacqueline E. Tate, Manish M. Patel, Umesh D. Parashar

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Background. Rotavirus vaccine was recommended for US infants in 2006. We estimated baseline prevaccine burden and monitored postvaccine trends in gastroenteritis-coded and rotavirus-coded hospitalizations among US children.

Methods. We analyzed data from the State Inpatient Databases (SID) for 29–44 US states over a 10-year period (2000–2009) to calculate gastroenteritis and rotavirus-coded hospitalization rates by age group, sex, and region, among children <5 years of age. By extrapolating observed pre- and postvaccine gastroenteritis hospitalization rates to the US population <5 years and based on the 2009 cost of a diarrhea hospitalization, we estimated national reductions in diarrhea hospitalizations and associated treatment costs.

Results. The prevaccine (2000–2006) annual average gastroenteritis-coded hospitalization rate among children <5 years of age was 74 per 10 000 (annual range, 71–82 per 10 000), and declined to 51 and 50 per 10 000 in 2008 and 2009, respectively (P < .001). The prevaccine (2000–2006) annual average rotavirus-coded hospitalization rate among children <5 years of age was 15 per 10 000 (annual range, 13–18 per 10 000), and declined to 5 and 6 per 10 000 in 2008 and 2009, respectively (P < .001). The decreases in rotavirus-coded hospitalization rates in 2008 and 2009 compared with rates in prevaccine years were observed among all age groups and US regions. Nationally, during 2008 and 2009 combined, we estimated a reduction of approximately 77 000 diarrhea hospitalizations and approximately $242 million in hospital costs.

Conclusions. Since implementation of the US rota-virus vaccination program, a marked reduction in diarrhea hospitalizations and related hospital charges has occurred among US children.


Evaluation Of Pneumonia Virus Of Mice As A Possible Human Pathogen, Linda G. Brock, Ruth A. Karron, Christine D. Krempl, Peter L. Collins, Ursula J. Buchholz May 2012

Evaluation Of Pneumonia Virus Of Mice As A Possible Human Pathogen, Linda G. Brock, Ruth A. Karron, Christine D. Krempl, Peter L. Collins, Ursula J. Buchholz

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Pneumonia virus of mice (PVM), a relative of human respiratory syncytial virus (RSV), causes respiratory disease in mice. There is serologic evidence suggesting widespread exposure of humans to PVM. To investigate replication in primates, African green monkeys (AGM) and rhesus macaques (n=4) were inoculated with PVM by the respiratory route. Virus was shed intermittently at low levels by a subset of animals, suggesting poor permissiveness. PVM efficiently replicated in cultured human cells and inhibited the type I interferon (IFN) response in these cells. This suggests that poor replication in nonhuman primates was not due to a general nonpermissiveness …


Genome-Wide Mirnaprofiling Of Mantle Cell Lymphoma Reveals A Distinct Subgroup With Poor Prognosis, Javeed Iqbal, Yulei Shen, Yanyan Liu, Kai Fu, Elaine S. Jaffe, Cuiling Liu, Zhongfeng Liu, Cynthia M. Lachel, Karen Deffenbacher, Timothy C. Greiner, Julie M. Vose, Sharathkumar Bhagavathi, Louis M. Staudt, Lisa Rimsza, Andreas Rosenwald, German Ott, Jan Delabie, Elias Campo, Rita M. Braziel, James R. Cook, Raymond R. Tubbs, Randy D. Gascoyne, James O. Armitage, Dennis D. Weisenburger, Timothy W. Mckeithan, Wing C. Chan May 2012

Genome-Wide Mirnaprofiling Of Mantle Cell Lymphoma Reveals A Distinct Subgroup With Poor Prognosis, Javeed Iqbal, Yulei Shen, Yanyan Liu, Kai Fu, Elaine S. Jaffe, Cuiling Liu, Zhongfeng Liu, Cynthia M. Lachel, Karen Deffenbacher, Timothy C. Greiner, Julie M. Vose, Sharathkumar Bhagavathi, Louis M. Staudt, Lisa Rimsza, Andreas Rosenwald, German Ott, Jan Delabie, Elias Campo, Rita M. Braziel, James R. Cook, Raymond R. Tubbs, Randy D. Gascoyne, James O. Armitage, Dennis D. Weisenburger, Timothy W. Mckeithan, Wing C. Chan

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miRNA deregulation has been implicated in the pathogenesis of mantle cell lymphoma (MCL). Using a high-throughput quantitative real-time PCR platform, we performed miRNA profiling on cyclin D1–positive MCL (n = 30) and cyclin D1–negative MCL (n =7) and compared them with small lymphocytic leukemia/ lymphoma (n =12), aggressive B-cell lymphomas (n =138), normal B-cell subsets, and stromal cells.We identified a 19-miRNA classifier that included 6 up-regulated miRNAs and 13 down regulated miRNA that was able to distinguish MCL from other aggressive lymphomas. Some of the up-regulated miRNAs are highly expressed in naive B cells. This miRNAclassifier …


Effectiveness Of Supported Employment For Veterans With Spinal Cord Injuries: Results From A Randomized Multisite Study, Lisa Ottomanelli, Lance L. Goetz, Alina Suris, Charles Mcgeough, Patricia L. Sinnott, Rich Toscano, Scott D. Barnett, Daisha J. Cipher, Lisa M. Lind, Thomas M. Dixon, Sally Ann Holmes, Anthony J. Kerrigan, Florian P. Thomas May 2012

Effectiveness Of Supported Employment For Veterans With Spinal Cord Injuries: Results From A Randomized Multisite Study, Lisa Ottomanelli, Lance L. Goetz, Alina Suris, Charles Mcgeough, Patricia L. Sinnott, Rich Toscano, Scott D. Barnett, Daisha J. Cipher, Lisa M. Lind, Thomas M. Dixon, Sally Ann Holmes, Anthony J. Kerrigan, Florian P. Thomas

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Ottomanelli L, Goetz LL, Suris A, McGeough C, Sinnott PL, Toscano R, Barnett SD, Cipher DJ, Lind LM, Dixon TM, Holmes SA, Kerrigan AJ, Thomas FP. Effectiveness of supported employment for veterans with spinal cord injuries: results from a randomized multisite study.

Objective: To examine whether supported employment (SE) is more effective than treatment as usual (TAU) in returning veterans to competitive employment after spinal cord injury (SCI).

Design: Prospective, randomized, controlled, multisite trial of SE versus TAU for vocational issues with 12 months of follow-up data.

Setting: SCI centers in the Veterans Health Administration.

Participants: …


Molecular Distinctions Between Pediatric And Adult Mature B-Cell Non-Hodgkin Lymphomas Identified Through Genomic Profiling, Karen Deffenbacher, Javeed Iqbal, Warren Sanger, Yulei Shen, Cynthia Lachel, Zhongfeng Liu, Yanyan Liu, Megan Lim, Sherrie Perkins, Kai Fu, Lynette Smith, James Lynch, Louis Staudt, Lisa M. Rimsza, Elaine Jaffe, Andreas Rosenwald, German Ott, Jan Delabie, Elias Campo, Randy Gascoyne, Mitchell Cairo, Dennis Weisenburger, Timothy Greiner, Thomas Gross, Wing Chan Apr 2012

Molecular Distinctions Between Pediatric And Adult Mature B-Cell Non-Hodgkin Lymphomas Identified Through Genomic Profiling, Karen Deffenbacher, Javeed Iqbal, Warren Sanger, Yulei Shen, Cynthia Lachel, Zhongfeng Liu, Yanyan Liu, Megan Lim, Sherrie Perkins, Kai Fu, Lynette Smith, James Lynch, Louis Staudt, Lisa M. Rimsza, Elaine Jaffe, Andreas Rosenwald, German Ott, Jan Delabie, Elias Campo, Randy Gascoyne, Mitchell Cairo, Dennis Weisenburger, Timothy Greiner, Thomas Gross, Wing Chan

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Burkitt lymphoma (BL) predominates in pediatric patients, whereas diffuse large B-cell lymphoma (DLBCL) is uncommon. In contrast to adults, BL and DLBCL are treated similarly in children and both entities have superior outcomes in children compared with adults. Gene expression profiling (GEP) and miRNA expression profiling clearly differentiated pediatric DLBCL from BL, forming distinct clusters regardless of patient age. However, pathway analysis of GEP data identified minor differences between corresponding pediatric and adult tumors. Predominance (6:1) of the germinal center B-cell subtype to activated B-cell subtype was found among pediatric DLBCL. Two cases were molecularly classified as primary mediastinal B-cell …


Genome-Wide Microrna Profiling Of Mantle Cell Lymphoma Reveal A Distinct Subgroup With Poor Prognosis, Javeed Iqbal, Yulei Shen, Yanyan Liu, Kai Fu, Elaine Jaffe, Cuiling Liu, Zhongfeng Liu, Cynthia Lachel, Karen Deffenbacher, Timothy Greiner, Julie Vose, Sharathkumar Bhagavathi, Louis Staudt, Lisa Rimsza, Andreas Rosenwald, German Ott, Jan Delabie, Elias Campo, Rita Braziel, James Cook, Raymond Tubbs, Randy Gascoyne, James Armitage, Dennis Weisenburger, Timothy Mckeithan, Wing Chan Apr 2012

Genome-Wide Microrna Profiling Of Mantle Cell Lymphoma Reveal A Distinct Subgroup With Poor Prognosis, Javeed Iqbal, Yulei Shen, Yanyan Liu, Kai Fu, Elaine Jaffe, Cuiling Liu, Zhongfeng Liu, Cynthia Lachel, Karen Deffenbacher, Timothy Greiner, Julie Vose, Sharathkumar Bhagavathi, Louis Staudt, Lisa Rimsza, Andreas Rosenwald, German Ott, Jan Delabie, Elias Campo, Rita Braziel, James Cook, Raymond Tubbs, Randy Gascoyne, James Armitage, Dennis Weisenburger, Timothy Mckeithan, Wing Chan

Public Health Resources

MicroRNA (miRNA) deregulation has been implicated in the pathogenesis of mantle cell lymphoma (MCL). Using a high-throughput quantitative real-time PCR platform, we performed miRNA profiling on cyclin D1- positive MCL (n=30) and cyclin D1-negative MCL (n=7) and compared them with small lymphocytic leukemia/lymphoma (SLL, n=12), aggressive B-cell lymphomas (n=138), normal B-cell subsets and stromal cells. We identified a 19-miRNA classifier which included six upregulated miRNAs (miR-135a, miR-708, miR-150, miR-363, miR-184, miR-342-5p) and 13 downregulated miRNAs, that was able to distinguish MCL from other aggressive lymphomas with >90% probability. Some of these upregulated miRNAs are highly expressed in naïve B-cells. MicroRNA …


Effects Of Leptin Replacement Alone And With Exendin-4 On Food Intake And Weight Regain In Weight-Reduced Diet-Induced Obese Rats, Roger Reidelberger, Alvin Haver, Prasanth K. Chelikani, Bettye Apenteng, Curtis Perriotte-Olson, Krista Anders, Sharalyn Steenson, James E. Blevins Apr 2012

Effects Of Leptin Replacement Alone And With Exendin-4 On Food Intake And Weight Regain In Weight-Reduced Diet-Induced Obese Rats, Roger Reidelberger, Alvin Haver, Prasanth K. Chelikani, Bettye Apenteng, Curtis Perriotte-Olson, Krista Anders, Sharalyn Steenson, James E. Blevins

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Reidelberger R, Haver A, Chelikani PK, Apenteng B, Perriotte-Olson C, Anders K, Steenson S, Blevins JE. Effects of leptin replacement alone and with exendin-4 on food intake and weight regain in weight-reduced diet-induced obese rats. Am J Physiol Endocrinol Metab 302: E1576–E1585, 2012. First published April 17, 2012; doi:10.1152/ajpendo.00058.2012.—Weight loss in obese humans produces a relative leptin deficiency, which is postulated to activate potent orexigenic and energy conservation mechanisms to restrict weight loss and promote weight regain. Here we determined whether leptin replacement alone or with GLP-1 receptor agonist exendin-4 attenuates weight regain or promotes greater weight loss in weight-reduced …


Benchmarking Us Department Of Veterans Affairs Dermatologic Services: Results From A National Survey, L. Kendall Krause, Leilani Townsend, Michael L. Orser, Jennifer Mulhausen, Jodi Duke, Weston T. Waxweiler, Robert P. Dellavalle Mar 2012

Benchmarking Us Department Of Veterans Affairs Dermatologic Services: Results From A National Survey, L. Kendall Krause, Leilani Townsend, Michael L. Orser, Jennifer Mulhausen, Jodi Duke, Weston T. Waxweiler, Robert P. Dellavalle

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Background: How well Department of Veterans Affairs (VA) dermatology services provide clinical care, medical education, and innovative research is a largely unexplored topic in the literature.

Objective: We sought to benchmark VA dermatology services by surveying VA dermatologists about their environment, resources, and the pros and cons of working in the VA.

Methods: Printed surveys were mailed to VA dermatologists and responses were compiled and analyzed.

Results: Of 105 dermatology services surveyed, 48% returned surveys completed by board-certified dermatologists (n = 50); 20 surveys completed by nondermatologists were excluded from the analysis. Most services trained …


The Association Between Depression And Anxiety And Use Of Oral Health Services And Tooth Loss, Catherine A. Okoro, Tara W. Strine, Paul I. Eke, Satvinder S. Dhingra, Lina S. Balluz Jan 2012

The Association Between Depression And Anxiety And Use Of Oral Health Services And Tooth Loss, Catherine A. Okoro, Tara W. Strine, Paul I. Eke, Satvinder S. Dhingra, Lina S. Balluz

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Objective: The purpose of this study is to examine the associations among depression, anxiety, use of oral health services, and tooth loss.

Methods: Data were analysed for 80 486 noninstitutionalized adults in 16 states who participated in the 2008 Behavioral Risk Factor Surveillance System. Binomial and multinomial logistic regression analyses were used to estimate predicted marginals, adjusted prevalence ratios, adjusted odds ratios (AOR) and their 95% confidence intervals (CI).

Results: The unadjusted prevalence for use of oral health services in the past year was 73.1% [standard error (SE), 0.3%]. The unadjusted prevalence by level of tooth loss …


Improving Outpatient Diabetes Care, Susan Kirsh, Michael Hein, Leonard Pogach, Gordon Schectman, Lauren Stevenson, Sharon Watts, Archana Radhakrishnan, John Chardos, David Aron Jan 2012

Improving Outpatient Diabetes Care, Susan Kirsh, Michael Hein, Leonard Pogach, Gordon Schectman, Lauren Stevenson, Sharon Watts, Archana Radhakrishnan, John Chardos, David Aron

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More than 20% of patients in the Veterans Health Administration (VHA) have diabetes; therefore, disseminating “best practices” in outpatient diabetes care is paramount. The authors’ goal was to identify such practices and the factors associated with their development. First, a national VHA diabetes registry with 2008 data identified clinical performance based on the percentage of patients with an A1c >9%. Facilities (n = 140) and community-based outpatient clinics (n = 582) were included and stratified into high, mid, and low performers. Semistructured telephone interviews (31) and site visits (5) were conducted. Low performers cited lack of teamwork between physicians and …


Most Physicians Were Eligible For Federal Incentives In 2011, But Few Had Ehr Systems That Met Meaningful-Use Criteria, Chun-Ju Hsiao, Sandra Decker, Esther Hing, Jane Sisk Jan 2012

Most Physicians Were Eligible For Federal Incentives In 2011, But Few Had Ehr Systems That Met Meaningful-Use Criteria, Chun-Ju Hsiao, Sandra Decker, Esther Hing, Jane Sisk

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As more physicians adopt electronic health record systems in their practices, policy interest is focusing on whether physicians are ready to meet the federal “meaningful use” criteria—a vital threshold to qualify for financial incentives. In our analysis of a 2011 nationally representative survey of office-based physicians, we found that 91 percent of physicians were eligible for Medicare or Medicaid meaningful-use incentives. About half of all physicians intended to apply. However, only 11 percent both intended to apply for the incentives and had electronic health record systems with the capabilities to support even two-thirds of the stage 1 core objectives required …


Clinical Research And Development Of Tuberculosis Diagnostics: Moving From Silos To Synergy, Payam Nahid, Peter S. Kim, Carlton A. Evans, David Alland, Michael Barer, Jane Diefenbach, Jerrold Ellner, Richard Hafner, Carol Dukes Hamilton, Michael F. Iademarco, Gregory Ireton, Michael E. Kimerling, Christian Lienhardt, William R. Mackenzie, Megan Murray, Mark D. Perkins, Jamie E. Posey, Teri Roberts, Christine Sizemore, Wendy S. Stevens, Laura Via, Sharon D. Williams, Wing Yew, Susan Swindells Jan 2012

Clinical Research And Development Of Tuberculosis Diagnostics: Moving From Silos To Synergy, Payam Nahid, Peter S. Kim, Carlton A. Evans, David Alland, Michael Barer, Jane Diefenbach, Jerrold Ellner, Richard Hafner, Carol Dukes Hamilton, Michael F. Iademarco, Gregory Ireton, Michael E. Kimerling, Christian Lienhardt, William R. Mackenzie, Megan Murray, Mark D. Perkins, Jamie E. Posey, Teri Roberts, Christine Sizemore, Wendy S. Stevens, Laura Via, Sharon D. Williams, Wing Yew, Susan Swindells

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The development, evaluation, and implementation of new and improved diagnostics have been identified as critical needs by human immunodeficiency virus (HIV) and tuberculosis researchers and clinicians alike. These needs exist in international and domestic settings and in adult and pediatric populations. Experts in tuberculosis and HIV care, researchers, healthcare providers, public health experts, and industry representatives, as well as representatives of pertinent US federal agencies (Centers for Disease Control and Prevention, Food and Drug Administration, National Institutes of Health, United States Agency for International Development) assembled at a workshop proposed by the Diagnostics Working Group of the Federal Tuberculosis Taskforce …


Replicating Adenovirus-Simian Immunodeficiency Virus (Siv) Vectors Efficiently Prime Siv-Specific Systemic And Mucosal Immune Responses By Targeting Myeloid Dendritic Cells And Persisting In Rectal Macrophages, Regardless Of Immunization Route, L. Jean Patterson, Seraphin Kuate, Mara Daltabuit-Test, Qingsheng Li, Peng Xiao, Katherine Mckinnon, Janet Dipasquale, Anthony Cristillo, David Venzon, Ashley Haase, Marjorie Robert-Guroff Jan 2012

Replicating Adenovirus-Simian Immunodeficiency Virus (Siv) Vectors Efficiently Prime Siv-Specific Systemic And Mucosal Immune Responses By Targeting Myeloid Dendritic Cells And Persisting In Rectal Macrophages, Regardless Of Immunization Route, L. Jean Patterson, Seraphin Kuate, Mara Daltabuit-Test, Qingsheng Li, Peng Xiao, Katherine Mckinnon, Janet Dipasquale, Anthony Cristillo, David Venzon, Ashley Haase, Marjorie Robert-Guroff

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Although priming with replicating adenovirus type 5 host range mutant (Ad5hr)-human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) recombinants, followed by HIV/SIV envelope boosting, has proven highly immunogenic, resulting in protection from SIV/simian-human immunodeficiency virus (SHIV) challenges, Ad5hr recombinant distribution, replication, and persistence have not been examined comprehensively in nonhuman primates. We utilized Ad5hr-green fluorescent protein and Ad5hr-SIV recombinants to track biodistribution and immunogenicity following mucosal priming of rhesus macaques by the intranasal/intratracheal, sublingual, vaginal, or rectal route. Ad recombinants administered by all routes initially targeted macrophages in bronchoalveolar lavage (BAL) fluid and rectal tissue, later extending to myeloid dendritic cells …


The Use Of Low-Calorie Sweeteners By Children: Implications For Weight Management, John Foreyt, Ronald Kleinman, Rebecca Brown, Rachel Lindstrom Jan 2012

The Use Of Low-Calorie Sweeteners By Children: Implications For Weight Management, John Foreyt, Ronald Kleinman, Rebecca Brown, Rachel Lindstrom

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The rise in pediatric obesity since the 1970s has been well established in the United States and is becoming a major concern worldwide. As a potential means to help slow the obesity epidemic, low-calorie sweeteners (LCS) have gained attention as dietary tools to assist in adherence to weight loss plans or prevention of excess weight gain. Observational studies tend to show positive correlations between LCS consumption and weight gain in children and adolescents. Although the data are intriguing, these epidemiologic studies do not establish that LCS cause weight gain, because there are likely many lifestyle and genetic differences between children …


Salmonella Enterica Serotype Enteritidis: Increasing Incidence Of Domestically Acquired Infections, Shua J. Chai, Patricia L. White, Sarah L. Lathrop, Suzanne M. Solghan, Carlota Medus, Beth Mcglinchey, Melissa Tobin-D'Angelo, Ruthanne Marcus, Barbara Mahon Jan 2012

Salmonella Enterica Serotype Enteritidis: Increasing Incidence Of Domestically Acquired Infections, Shua J. Chai, Patricia L. White, Sarah L. Lathrop, Suzanne M. Solghan, Carlota Medus, Beth Mcglinchey, Melissa Tobin-D'Angelo, Ruthanne Marcus, Barbara Mahon

Public Health Resources

Background. Salmonella enterica causes an estimated 1 million cases of domestically acquired foodborne illness in humans annually in the United States; Enteritidis (SE) is the most common serotype. Public health authorities, regulatory agencies, food producers, and food processors need accurate information about rates and changes in SE infection to implement and evaluate evidence-based control policies and practices.

Methods. We analyzed the incidence of human SE infection during 1996–2009 in the Foodborne Diseases Active Surveillance Network (FoodNet), an active, population-based surveillance system for laboratory-confirmed infections. We compared FoodNet incidence with passively collected data from complementary surveillance systems and with …


The Structure Of Posttraumatic Psychopathology In Veterans Attending Primary Care, David Forbes, Jon D. Elhai, Emma Lockwood, Mark Creamer, B. Christopher Frueh, Kathryn M. Magruder Jan 2012

The Structure Of Posttraumatic Psychopathology In Veterans Attending Primary Care, David Forbes, Jon D. Elhai, Emma Lockwood, Mark Creamer, B. Christopher Frueh, Kathryn M. Magruder

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This study attempted to extend research indicating that posttraumatic stress disorder (PTSD) factors of Re-experiencing, Avoidance and Hyperarousal are more related to Fear/phobic disorders, while PTSD Dysphoria is more related to Anxious-Misery disorders. Trauma exposure, PTSD and comorbidity data for 668 veteran patients were analysed using confirmatory factor analyses and relative strengths of the relationships between PTSD factors and the Fear and Anxious-Misery factors were assessed. Combining Simms, Watson, and Doebbeling’s (2002) model of PTSD symptoms and Krueger’s (1999) Fear/Anxious Misery model of mood and anxiety disorders fit the data well. Contrary to previous research, PTSD Reexperiencing, Avoidance and Hyperarousal …


Trends In Total Laryngectomy In The Era Of Organ Preservation: A Population- Based Study, Patrick Tate Maddox, Louise Davies Jan 2012

Trends In Total Laryngectomy In The Era Of Organ Preservation: A Population- Based Study, Patrick Tate Maddox, Louise Davies

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Objective. To describe time trends in total laryngectomy health services utilization across the United States, such as rates of surgery, cost, length of stay, and insurance payer, and to compare this to important milestones in recommendations for laryngeal cancer treatment.

Study Design. Population-based cohort study

Setting. Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) 1997-2008: stratified sample of all US hospital discharges.

Subjects and Methods. All patients with the principal procedure of complete laryngectomy. The unit of analysis was the discharge.

Results. Between 1997 and 2008, the number of laryngectomies done in the United States …


Women At War: Understanding How Women Veterans Cope With Combat And Military Sexual Trauma, Kristin M. Mattocks, Sally G. Haskell, Erin E. Krebs, Amy C. Justice, Elizabeth M. Yano, Cynthia Brandt Jan 2012

Women At War: Understanding How Women Veterans Cope With Combat And Military Sexual Trauma, Kristin M. Mattocks, Sally G. Haskell, Erin E. Krebs, Amy C. Justice, Elizabeth M. Yano, Cynthia Brandt

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The wars in Iraq (Operation Iraqi Freedom, OIF) and Afghanistan (Operation Enduring Freedom, OEF) have engendered a growing population of US female veterans, with women now comprising 15% of active US duty military personnel. Women serving in the military come under direct fire and experience combatrelated injuries and trauma, and are also often subject to in-service sexual assaults and sexual harassment. However, little is known regarding howwomen veterans cope with these combat and military sexual trauma experiences once they return from deployment. To better understand their experiences, we conducted semi-structured interviews with nineteen OEF/OIF women veterans between JanuaryeNovember 2009. Women …


Factors Associated With Screening Or Treatment Initiation Among Male United States Veterans At Risk For Osteoporosis Fracture, Richard E. Nelson, Jonathan R. Nebeker, Brian C. Sauer, Joanne Lafleur Jan 2012

Factors Associated With Screening Or Treatment Initiation Among Male United States Veterans At Risk For Osteoporosis Fracture, Richard E. Nelson, Jonathan R. Nebeker, Brian C. Sauer, Joanne Lafleur

Public Health Resources

Male osteoporosis continues to be under-recognized and undertreated in men. An understanding of which factors cue clinicians about osteoporosis risk in men, and which do not, is needed to identify areas for improvement. This study sought to measure the association of a provider's recognition of osteoporosis with patient information constructs that are available at the time of each encounter. Using clinical and administrative data from the Veterans Health Administration system, we used a stepwise procedure to construct prognostic models for a combined outcome of osteoporosis diagnosis, treatment, or a bone mineral density (BMD) test order using time-varying covariates and Cox …