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Labrad : Vol 43, Issue 3 - December 2017, Aga Khan University Hospital, Karachi Dec 2017

Labrad : Vol 43, Issue 3 - December 2017, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

  • Levey Jennings Chart and Guide to use Westgard Rules
  • Quality Assurance in Frozen Section Studies
  • Performance Improvement Monitors in Histology
  • Quality Assurance in Immunohistochemistry: The Way We Do It
  • Quality Assurance in Laboratory Biosafety
  • Quality Control of Culture Media Used in Clinical Microbiology
  • Quality Assurance (QA) in Qualitative Tests in the Clinical Laboratory
  • Radiology Pathology Correlation
  • Quality Requirements for Reporting Sickle Haemoglobin
  • Meeting Report of International Federation of Clinical Chemistry (IFCC) Conferences- 2017


Hypermucoviscous Klebsiella Syndrome It's In The Community!, Muneeba Ahsan Sayeed, Nida Latif, Syed Faisal Mahmood Dec 2017

Hypermucoviscous Klebsiella Syndrome It's In The Community!, Muneeba Ahsan Sayeed, Nida Latif, Syed Faisal Mahmood

Section of Internal Medicine

Hypermucoviscous Klebsiella syndrome is a unique syndrome caused by a new variant of Klebsiella pneumoniae (KP), characterized by abscess formation at distant body sites. This emerging KP strain is different from the usual classic strains in having the rmp gene which increases capsule formation making this strain resistant to phagocytosis and helping in its dissemination to distant organs. A 50 years old diabetic man presented with facial swelling after dental procedure which progressively increased despite being on antibiotics. On examination he was febrile, had neck swelling with signs of inflammation and tender hepatomegaly. Ultrasonography showed submental and liver abscesses which …


Cerebrospinal Fluid Kynurenine And Kynurenic Acid Concentrations Are Associated With Coma Duration And Long-Term Neurocognitive Impairment In Ugandan Children With Cerebral Malaria, Dag Holmberg, Elisabeth Franzén-Röhl, Richard Idro, Robert Opoka, Paul Bangirana, Carl Sellgren, Anna Färnert, Lilly Schwieler, Göran Engberg, Chandy John Dec 2017

Cerebrospinal Fluid Kynurenine And Kynurenic Acid Concentrations Are Associated With Coma Duration And Long-Term Neurocognitive Impairment In Ugandan Children With Cerebral Malaria, Dag Holmberg, Elisabeth Franzén-Röhl, Richard Idro, Robert Opoka, Paul Bangirana, Carl Sellgren, Anna Färnert, Lilly Schwieler, Göran Engberg, Chandy John

Paediatrics and Child Health, East Africa

Background: One-fourth of children with cerebral malaria (CM) retain cognitive sequelae up to 2 years after acute disease. The kynurenine pathway of the brain, forming neuroactive metabolites, e.g. the NMDA-receptor antagonist kynurenic acid (KYNA), has been implicated in long-term cognitive dysfunction in other CNS infections. In the present study, the association between the kynurenine pathway and neurologic/cognitive complications in children with CM was investigated.

Methods: Cerebrospinal fuid (CSF) concentrations of KYNA and its precursor kynurenine in 69 Ugandan children admitted for CM to Mulago Hospital, Kampala, Uganda, between 2008 and 2013 were assessed. CSF kynurenine and KYNA were compared to …


Understanding Biological Mechanisms Underlying Adverse Birth Outcomes In Developing Countries: Protocol For A Prospective Cohort (Amanhi Bio-Banking) Study, Abdullah H. Baqui, Rasheda Khanam, Fyezah Jehan, Muhammad Imran Nisar, Atiya Hussain, Muhammad Ilyas, Aneeta Hotwani, Muhammad Sajid, Shahida Qureshi, Anita K. M. Zaidi Dec 2017

Understanding Biological Mechanisms Underlying Adverse Birth Outcomes In Developing Countries: Protocol For A Prospective Cohort (Amanhi Bio-Banking) Study, Abdullah H. Baqui, Rasheda Khanam, Fyezah Jehan, Muhammad Imran Nisar, Atiya Hussain, Muhammad Ilyas, Aneeta Hotwani, Muhammad Sajid, Shahida Qureshi, Anita K. M. Zaidi

Department of Paediatrics and Child Health

Objectives: The AMANHI study aims to seek for biomarkers as predictors of important pregnancy-related outcomes, and establish a biobank in developing countries for future research as new methods and technologies become available.
Methods: AMANHI is using harmonised protocols to enrol 3000 women in early pregnancies (8-19 weeks of gestation) for population-based follow-up in pregnancy up to 42 days postpartum in Bangladesh, Pakistan and Tanzania, with collection taking place between August 2014 and June 2016. Urine pregnancy tests will be used to confirm reported or suspected pregnancies for screening ultrasound by trained sonographers to accurately date the pregnancy. Trained study field …


Cxc Chemokines Exhibit Bactericidal Activity Against Multidrug-Resistant Gram-Negative Pathogens, Erum Khan, Matthew A. Crawford, Debra J. Fisher, Lisa M. Leung, Sara Lomonaco, Christine Lascols, Antonio Cannatelli,, Gian Maria Rossolini, Yohei Doi, David R. Goodlett Dec 2017

Cxc Chemokines Exhibit Bactericidal Activity Against Multidrug-Resistant Gram-Negative Pathogens, Erum Khan, Matthew A. Crawford, Debra J. Fisher, Lisa M. Leung, Sara Lomonaco, Christine Lascols, Antonio Cannatelli,, Gian Maria Rossolini, Yohei Doi, David R. Goodlett

Department of Pathology and Laboratory Medicine

The continued rise and spread of antimicrobial resistance among bacterial pathogens pose a serious challenge to global health. Countering antimicrobial-resistant pathogens requires a multifaceted effort that includes the discovery of novel therapeutic approaches. Here, we establish the capacity of the human CXC chemokines CXCL9 and CXCL10 to kill multidrug-resistant Gram-negative bacteria, including New Delhi metallo-beta-lactamase-1-producing Klebsiella pneumoniae and colistin-resistant members of the family Enterobacteriaceae that harbor the mobile colistin resistance protein MCR-1 and thus possess phosphoethanolamine-modified lipid A. Colistin-resistant K. pneumoniae isolates affected by genetic mutation of the PmrA/PmrB two-component system, a chromosomally encoded regulator of lipopolysaccharide modification, and containing …


Memory Potential, Molecular Characterization, And Translational Applications Of The Novel Theo/Tceo T Cell Phenotype, Todd Bartkowiak, Todd Bartkowiak Dec 2017

Memory Potential, Molecular Characterization, And Translational Applications Of The Novel Theo/Tceo T Cell Phenotype, Todd Bartkowiak, Todd Bartkowiak

Dissertations and Theses (Open Access)

T cells comprise a substantial arm of the immune system and are exquisitely adapted to combat pathogens and tumors. The inflammatory environment largely dictates the nature of T cell response. A hallmark of T cell-mediated immunity is formation of immunological memory; the ability to respond more potently to re-encounter with pathogens. The immune system is also capable of recognizing tumors as foreign, much like viral or bacterial pathogens. Tumors have evolved, though, to generate an immunosuppressive environment to avoid destruction. The field of immunotherapy seeks to overcome immune suppression, in part by targeting T cell co-receptors on the cell surface …


Dynamic Assessment Of Nk Cell Interactions With Pediatric Tumor Cells To Predict Response To Immunotherapy, Arianexys Aquino Lopez Dec 2017

Dynamic Assessment Of Nk Cell Interactions With Pediatric Tumor Cells To Predict Response To Immunotherapy, Arianexys Aquino Lopez

Dissertations and Theses (Open Access)

Due to Natural Killer (NK) cells’ capacity to target tumor cells without prior sensitization, adoptive NK cell therapy represents a promising immunotherapy approach for pediatric cancer patients. Our laboratory has developed an NK cell expansion protocol that generates large quantities of NK cells for therapeutic infusion. Given that NK cells are heterogeneous, with variable receptor expression and potential to target tumor cells, the purpose of my study was to determine whether subpopulations of NK cells with enhanced anti-tumor potential could be identified for increased potency of the NK cell infusion product. In addition, we previously showed that our expanded NK …


Membrane Bound Il21 Promotes Natural Killer Cell Expansion Through Mir 124-3p Mediated Regulation, Anitha Somanchi Dec 2017

Membrane Bound Il21 Promotes Natural Killer Cell Expansion Through Mir 124-3p Mediated Regulation, Anitha Somanchi

Dissertations and Theses (Open Access)

Natural Killer (NK) cells are cells of the innate immune system that act as first line of defense against viral infections and participate in tumor immune surveillance. NK cells do not cause graft versus host disease (GvHD), or require prior antigen exposure to exert anti-tumor activity, hence are an attractive choice for immunotherapy applications. Owing to small numbers of NK cells in peripheral blood (1-32%, with a 6% median), ex vivo expansion of NK cells is critical for NK cell adoptive immunotherapy, various expansion platforms have been explored over the decades. We developed a robust platform for ex vivo expansion …


Identifying Constraints For Hospital Infection Control Management Via Mckinsey 7s Framework In Pakistan, Shagufta Perveen, Shifa Salman Habib Dec 2017

Identifying Constraints For Hospital Infection Control Management Via Mckinsey 7s Framework In Pakistan, Shagufta Perveen, Shifa Salman Habib

Community Health Sciences

Background: In Pakistan, structured guidelines for hospital infection control and prevention are deficient in most public sector facilities. There is dearth of literature available on management of hospital-care acquired infections and related issues. This study aims to understand infection control management as a proxy measure for quality of health care provided at a public sector tertiary care hospital in Karachi, Pakistan. In this study, we identify barriers to implementation of infection control measures and highlight key areas for quality improvement.
Methods: A cross sectional study was carried out in 2008 using qualitative research methods. In-depth interviews were conducted with hospital …


Outbreak Response And Incident Management: Shea Guidance And Resources For Healthcare Epidemiologists In United States Acute-Care Hospitals., David B Banach, B Lynn Johnston, Duha Al-Zubeidi, Allison H Bartlett, Susan Casey Bleasdale, Valerie M Deloney, Kyle B Enfield, Judith A Guzman-Cottrill, Christopher Lowe, Luis Ostrosky-Zeichner, Kyle J Popovich, Payal K Patel, Karen Ravin, Theresa Rowe, Erica S Shenoy, Scott Stienecker Md, Pritish K Tosh, Kavita K Trivedi Dec 2017

Outbreak Response And Incident Management: Shea Guidance And Resources For Healthcare Epidemiologists In United States Acute-Care Hospitals., David B Banach, B Lynn Johnston, Duha Al-Zubeidi, Allison H Bartlett, Susan Casey Bleasdale, Valerie M Deloney, Kyle B Enfield, Judith A Guzman-Cottrill, Christopher Lowe, Luis Ostrosky-Zeichner, Kyle J Popovich, Payal K Patel, Karen Ravin, Theresa Rowe, Erica S Shenoy, Scott Stienecker Md, Pritish K Tosh, Kavita K Trivedi

Hospital Medicine

This expert guidance document was developed as a resource to provide healthcare epidemiologists working in acute-care hospitals with a high-level overview of incident management for infectious diseases outbreaks and to prepare them to work within an emergency response framework. It addresses how the epidemiologist’s skills and expertise apply to scenarios that require enhanced preparedness and response efforts, eg, when pathogens associated with outbreaks are poorly characterized or when outbreaks require additional interventions including, but not limited to, healthcare personnel education, enhanced infection prevention and control measures, added staffing, supplies, and resources, adjustments to clinical and support activities, and external communications. …


Fremanezumab For The Preventive Treatment Of Chronic Migraine., Stephen D. Silberstein, David W. Dodick, Marcelo E. Bigal, Paul P. Yeung, Peter J. Goadsby, Tricia Blankenbiller, Melissa Grozinski-Wolff, Ronghua Yang, Yuju Ma, Ernesto Aycardi Nov 2017

Fremanezumab For The Preventive Treatment Of Chronic Migraine., Stephen D. Silberstein, David W. Dodick, Marcelo E. Bigal, Paul P. Yeung, Peter J. Goadsby, Tricia Blankenbiller, Melissa Grozinski-Wolff, Ronghua Yang, Yuju Ma, Ernesto Aycardi

Department of Neurology Faculty Papers

BACKGROUND: Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP), is being investigated as a preventive treatment for migraine. We compared two fremanezumab dose regimens with placebo for the prevention of chronic migraine.

METHODS: In this phase 3 trial, we randomly assigned patients with chronic migraine (defined as headache of any duration or severity on ≥15 days per month and migraine on ≥8 days per month) in a 1:1:1 ratio to receive fremanezumab quarterly (a single dose of 675 mg at baseline and placebo at weeks 4 and 8), fremanezumab monthly (675 mg at baseline and 225 mg at …


Psoas Abscess Masquerading As A Prosthetic Hip Infection: A Case Report, Muhammad Atif, Azeem Tariq Malik, Shahryar Noordin Nov 2017

Psoas Abscess Masquerading As A Prosthetic Hip Infection: A Case Report, Muhammad Atif, Azeem Tariq Malik, Shahryar Noordin

Section of Orthopaedic Surgery

Introduction: Psoas abscess is an unusual condition and is defined as a collection of pus in the iliopsoas compartment. Due to the unique anatomy of psoas muscle it forms a conduit for spread of infection from upper part of body to hip joint in neglected cases.
Case Presentation: A 67year old lady presented with left groin pain for three weeks. She underwent an uncemented unipolar hemiarthoplasty eight years back. Currently, she developed fever and was unable to do any active left hip range of motion. Passive motion of the left hip was restricted to 30° flexion, no internal rotation, 5° …


Development Of A Broadly Protective Modified-Live Virus Vaccine Candidate Against Porcine Reproductive And Respiratory Syndrome Virus, Haiyan Sun, Aspen Workman, Fernando A. Osorio, David J. Steffen, Hiep L.X. Vu Nov 2017

Development Of A Broadly Protective Modified-Live Virus Vaccine Candidate Against Porcine Reproductive And Respiratory Syndrome Virus, Haiyan Sun, Aspen Workman, Fernando A. Osorio, David J. Steffen, Hiep L.X. Vu

Nebraska Center for Virology: Faculty Publications

Modified-live virus (MLV) vaccines are widely used to protect pigs against porcine reproductive and respiratory syndrome virus (PRRSV). However, current MLV vaccines do not confer adequate levels of heterologous protection, presumably due to the substantial genetic diversity of PRRSV isolates circulating in the field. To overcome this genetic variation challenge, we recently generated a synthetic PRRSV strain containing a consensus genomic sequence of PRRSV-2. We demonstrated that our synthetic PRRSV strain confers unprecedented levels of heterologous protection. However, the synthetic PRRSV strain at passage 1 (hereafter designated CON-P1) is highly virulent and therefore, is not suitable to be used as …


Managing Toxicities Associated With Immune Checkpoint Inhibitors: Consensus Recommendations From The Society For Immunotherapy Of Cancer (Sitc) Toxicity Management Working Group., I. Puzanov, A. Diab, K. Abdallah, C. O. Bingham, C. Brogdon, R. Dadu, L. Hamad, S. Kim, M. E. Lacouture, N. R. Leboeuf, D. Lenihan, C. Onofrei, V. Shannon, R. Sharma, A. W. Silk, D. Skondra, M. E. Suarez-Almazor, Y. Wang, K. Wiley, H. L. Kaufman, M. S. Ernstoff, J. Anderson, K. Lehman, D. Reshef, A. Saylors, M. Turner, I. Waxman, D. Arrindell, S. Andrews, J. Ballesteros, J. Boyer, I. Cotarla, M. Dawson, T. Goswami, V. Hayreh, W. Holmes, Z. Rasheed, M. Sarkeshik, J. Schreiber, K. Shafer-Weaver, D. Chen, S. Ley-Acosta, D. Chonzi, W. Go, R. Cunha, J. L. Gulley, L. Wood, M. Davies, Adam Dicker, L. Eifler, N. Gregory, A. Ferguson, C. Ferlini, S. Frankel, C. Gochett, J. Goldberg, K. Patel, D. Wariabharaj, P. Goncalves, N. Helie, J. Y. Hsu, R. Ibrahim, C. Larocca, O. Lambotte, J. Luke, J. Mcclure, E. Michelon, M. Nakamura, B. Piperdi, J. Riemer, C. Robert, W. Sharfman, E. Sharon, R. Sherry, C. Simonson, C. Thomas, E. Trehu, J. A. Thompson, D. Tresnan, L. Zhang, P. Zheng Nov 2017

Managing Toxicities Associated With Immune Checkpoint Inhibitors: Consensus Recommendations From The Society For Immunotherapy Of Cancer (Sitc) Toxicity Management Working Group., I. Puzanov, A. Diab, K. Abdallah, C. O. Bingham, C. Brogdon, R. Dadu, L. Hamad, S. Kim, M. E. Lacouture, N. R. Leboeuf, D. Lenihan, C. Onofrei, V. Shannon, R. Sharma, A. W. Silk, D. Skondra, M. E. Suarez-Almazor, Y. Wang, K. Wiley, H. L. Kaufman, M. S. Ernstoff, J. Anderson, K. Lehman, D. Reshef, A. Saylors, M. Turner, I. Waxman, D. Arrindell, S. Andrews, J. Ballesteros, J. Boyer, I. Cotarla, M. Dawson, T. Goswami, V. Hayreh, W. Holmes, Z. Rasheed, M. Sarkeshik, J. Schreiber, K. Shafer-Weaver, D. Chen, S. Ley-Acosta, D. Chonzi, W. Go, R. Cunha, J. L. Gulley, L. Wood, M. Davies, Adam Dicker, L. Eifler, N. Gregory, A. Ferguson, C. Ferlini, S. Frankel, C. Gochett, J. Goldberg, K. Patel, D. Wariabharaj, P. Goncalves, N. Helie, J. Y. Hsu, R. Ibrahim, C. Larocca, O. Lambotte, J. Luke, J. Mcclure, E. Michelon, M. Nakamura, B. Piperdi, J. Riemer, C. Robert, W. Sharfman, E. Sharon, R. Sherry, C. Simonson, C. Thomas, E. Trehu, J. A. Thompson, D. Tresnan, L. Zhang, P. Zheng

Department of Radiation Oncology Faculty Papers

Cancer immunotherapy has transformed the treatment of cancer. However, increasing use of immune-based therapies, including the widely used class of agents known as immune checkpoint inhibitors, has exposed a discrete group of immune-related adverse events (irAEs). Many of these are driven by the same immunologic mechanisms responsible for the drugs' therapeutic effects, namely blockade of inhibitory mechanisms that suppress the immune system and protect body tissues from an unconstrained acute or chronic immune response. Skin, gut, endocrine, lung and musculoskeletal irAEs are relatively common, whereas cardiovascular, hematologic, renal, neurologic and ophthalmologic irAEs occur much less frequently. The majority of irAEs …


Comparison Of Outcomes Of Antibiotic Drugs And Appendectomy (Coda) Trial: A Protocol For The Pragmatic Randomised Study Of Appendicitis Treatment., Giana H Davidson, David R Flum, David A Talan, Larry G Kessler, Danielle C Lavallee, Bonnie J Bizzell, Farhood Farjah, Skye D Stewart, Anusha Krishnadasan, Erin E Carney, Erika M Wolff, Bryan A Comstock, Sarah E Monsell, Patrick J Heagerty, Annie P Ehlers, Daniel A Deugarte, Amy H Kaji, Heather L Evans, Julianna T Yu, Katherine Mandell, Ian C Doten, Kevin S Clive, Karen M Mcgrane, Brandon C Tudor, Careen S Foster, Darin J Saltzman, Richard C Thirlby, Erin O Lange, Amber K Sabbatini, Gregory J Moran Nov 2017

Comparison Of Outcomes Of Antibiotic Drugs And Appendectomy (Coda) Trial: A Protocol For The Pragmatic Randomised Study Of Appendicitis Treatment., Giana H Davidson, David R Flum, David A Talan, Larry G Kessler, Danielle C Lavallee, Bonnie J Bizzell, Farhood Farjah, Skye D Stewart, Anusha Krishnadasan, Erin E Carney, Erika M Wolff, Bryan A Comstock, Sarah E Monsell, Patrick J Heagerty, Annie P Ehlers, Daniel A Deugarte, Amy H Kaji, Heather L Evans, Julianna T Yu, Katherine Mandell, Ian C Doten, Kevin S Clive, Karen M Mcgrane, Brandon C Tudor, Careen S Foster, Darin J Saltzman, Richard C Thirlby, Erin O Lange, Amber K Sabbatini, Gregory J Moran

Articles, Abstracts, and Reports

INTRODUCTION: Several European studies suggest that some patients with appendicitis can be treated safely with antibiotics. A portion of patients eventually undergo appendectomy within a year, with 10%-15% failing to respond in the initial period and a similar additional proportion with suspected recurrent episodes requiring appendectomy. Nearly all patients with appendicitis in the USA are still treated with surgery. A rigorous comparative effectiveness trial in the USA that is sufficiently large and pragmatic to incorporate usual variations in care and measures the patient experience is needed to determine whether antibiotics are as good as appendectomy.

OBJECTIVES: The Comparing Outcomes of …


Niemann-Pick Type C Disease, Sameh Morkous Md, Faan Nov 2017

Niemann-Pick Type C Disease, Sameh Morkous Md, Faan

Department of Pediatrics

No abstract provided.


Modelling Stunting In List: The Effect Of Applying Smoothing To Linear Growth Data, Simon Cousens, Jamie Perin, Parul Christian, Lee Shu-Fune Wu, Sajid Bashir Soofi, Zulfiqar Ahmed Bhutta, Claudio Lanata, Richard L. Guerrant, Aldo A. M. Lima, Kåre Mølbak Nov 2017

Modelling Stunting In List: The Effect Of Applying Smoothing To Linear Growth Data, Simon Cousens, Jamie Perin, Parul Christian, Lee Shu-Fune Wu, Sajid Bashir Soofi, Zulfiqar Ahmed Bhutta, Claudio Lanata, Richard L. Guerrant, Aldo A. M. Lima, Kåre Mølbak

Department of Paediatrics and Child Health

Background: The Lives Saved Tool (LiST) is a widely used resource for evidence-based decision-making regarding health program scale-up in low- and middle-income countries. LiST estimates the impact of specified changes in intervention coverage on mortality and stunting among children under 5 years of age. We aimed to improve the estimates of the parameters in LiST that determine the rate at which the effects of interventions to prevent stunting attenuate as children get older.
Methods: We identified datasets with serial measurements of children's lengths or heights and used random effects models and restricted cubic splines to model the growth trajectories of …


Water, Sanitation And Hygiene Interventions For Acute Childhood Diarrhea: A Systematic Review To Provide Estimates For The Lives Saved Tool, Nazia Darvesh, Jai K. Das, Tyler Vaivada, Michelle F. Gaffey, Kumanan Rasanathan, Zulfiqar Ahmed Bhutta Nov 2017

Water, Sanitation And Hygiene Interventions For Acute Childhood Diarrhea: A Systematic Review To Provide Estimates For The Lives Saved Tool, Nazia Darvesh, Jai K. Das, Tyler Vaivada, Michelle F. Gaffey, Kumanan Rasanathan, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

Background: In the Sustainable Development Goals (SDGs) era, there is growing recognition of the responsibilities of non-health sectors in improving the health of children. Interventions to improve access to clean water, sanitation facilities, and hygiene behaviours (WASH) represent key opportunities to improve child health and well-being by preventing the spread of infectious diseases and improving nutritional status.
Methods: We conducted a systematic review of studies evaluating the effects of WASH interventions on childhood diarrhea in children 0–5 years old. Searches were run up to September 2016. We screened the titles and abstracts of retrieved articles, followed by screening of the …


Lmp1 Signaling Pathway Activates Irf4 In Latent Ebv Infection And A Positive Circuit Between Pi3k And Src Is Required, Ling Wang, Junping Ren, Guang Li, Jonathan P. Moorman, Zhi Q. Yao, Shunbin Ning Nov 2017

Lmp1 Signaling Pathway Activates Irf4 In Latent Ebv Infection And A Positive Circuit Between Pi3k And Src Is Required, Ling Wang, Junping Ren, Guang Li, Jonathan P. Moorman, Zhi Q. Yao, Shunbin Ning

ETSU Faculty Works

Interferon (IFN) regulatory factors (IRFs) have crucial roles in immune regulation and oncogenesis. We have recently shown that IRF4 is activated through c-Src-mediated tyrosine phosphorylation in virus-transformed cells. However, the intracellular signaling pathway triggering Src activation of IRF4 remains unknown. In this study, we provide evidence that Epstein–Barr virus (EBV) latent membrane protein 1 (LMP1) promotes IRF4 phosphorylation and markedly stimulates IRF4 transcriptional activity, and that Src mediates LMP1 activation of IRF4. As to more precise mechanism, we show that LMP1 physically interacts with c-Src, and the phosphatidylinositol 3 kinase (PI3K) subunit P85 mediates their interaction. Depletion of P85 by …


Efficacy Of An Adenoviral Vectored Multivalent Centralized Influenza Vaccine, Amy Lingel, Brianna L. Bullard, Eric A. Weaver Nov 2017

Efficacy Of An Adenoviral Vectored Multivalent Centralized Influenza Vaccine, Amy Lingel, Brianna L. Bullard, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Mice were immunized with Adenovirus expressing the H1-con, H2-con, H3-con and H5-con HA consensus genes in combination (multivalent) and compared to mice immunized with the traditional 2010–2011 FluZone and FluMist seasonal vaccines. Immunized mice were challenged with 10–100 MLD50 of H1N1, H3N1, H3N2 and H5N1 influenza viruses. The traditional vaccines induced robust levels of HA inhibition (HI) titers, but failed to protect against five different heterologous lethal influenza challenges. Conversely, the multivalent consensus vaccine (1 × 1010 virus particles (vp)/mouse) induced protective HI titers of ≥40 against 8 of 10 influenza viruses that represent a wide degree of divergence within …


"Toll-Free" Pathways For Production Of Type I Interferons, Ling Wang, Shunbin Ning Nov 2017

"Toll-Free" Pathways For Production Of Type I Interferons, Ling Wang, Shunbin Ning

ETSU Faculty Works

Pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) are recognized by different cellular pathogen recognition receptors (PRRs), which are expressed on cell membrane or in the cytoplasm of cells of the innate immune system. Nucleic acids derived from pathogens or from certain cellular conditions represent a large category of PAMPs/DAMPs that trigger production of type I interferons (IFN-I) in addition to pro-inflammatory cytokines, by specifically binding to intracellular Toll-like receptors or cytosolic receptors. These cytosolic receptors, which are not related to TLRs and we call them "Toll-free" receptors, include the RNA-sensing RIG-I like receptors (RLRs), the DNA-sensing HIN200 family, …


Six-Year Experience Of Influenza Vaccination As A Condition Of Employment For A Large Regional Health Care System, John R. Brill, Mark Hermanoff, Angela Tonozzi, Mary Jo Capodice, Jennifer Farrar, Zarina Dawoodbhai Nov 2017

Six-Year Experience Of Influenza Vaccination As A Condition Of Employment For A Large Regional Health Care System, John R. Brill, Mark Hermanoff, Angela Tonozzi, Mary Jo Capodice, Jennifer Farrar, Zarina Dawoodbhai

Journal of Patient-Centered Research and Reviews

Background: Influenza remains a significant contributor to morbidity and mortality in the United States. Health care workers (HCW) can be both victims and vectors of influenza. Influenza vaccination of HCW is protective for both caregivers and patients, but voluntary programs generally fail to achieve rates recommended by the Centers for Disease Control and Prevention. Despite a complex, multifaceted influenza program initiated in 1996 that included significant education and promotion as well as free on-site vaccination, annual Aurora Health Care caregiver immunization rates remained in the mid-70s until adoption of a “condition of employment” strategy in 2011.

Purpose: Discuss the annual …


Fmt Placed By Colonoscopy: Systematic Review And Meta-Analysis, Nadia Huq, Veena Kumaravel, Aboud Affi, Maharaj Singh Nov 2017

Fmt Placed By Colonoscopy: Systematic Review And Meta-Analysis, Nadia Huq, Veena Kumaravel, Aboud Affi, Maharaj Singh

Journal of Patient-Centered Research and Reviews

Background: Fecal transplants are successful in the treatment of recurrent or refractory Clostridium difficile infections (CDI), but there is no consensus on the best method of instillation. Studies have shown greater success with lower gastrointestinal tract placement, but technical aspects of placement are not validated.

Purpose: This review aims to identify common traits and procedural techniques of successful fecal microbiota transplant (FMT) therapy via colonoscopy.

Methods: An electronic search was conducted using OVID Medline and PubMed for articles published from January 2010 to January 2016. The primary outcome of interest was cure by FMT placed via colonoscopy.

Results: Of the …


Nlrp10 Enhances Cd4+ T-Cell-Mediated Ifnγ Response Via Regulation Of Dendritic Cell-Derived Il-12 Release, Maurizio Vacca, Julia Böhme, Lisa Zambetti, Hanif Javanmard Khameneh, Bhairav S. Paleja, Federica Laudisi, Adrian W. S. Ho, Kurt Neo, Keith Weng Kit Leong, Mardiana Marzuki, Bernett Lee, Michael Poidinger, Laura Santambrogio, Liana Tsenova, Francesca Zolezzi, Gennaro De Libero, Amit Singhal, Alessandra Mortellaro Nov 2017

Nlrp10 Enhances Cd4+ T-Cell-Mediated Ifnγ Response Via Regulation Of Dendritic Cell-Derived Il-12 Release, Maurizio Vacca, Julia Böhme, Lisa Zambetti, Hanif Javanmard Khameneh, Bhairav S. Paleja, Federica Laudisi, Adrian W. S. Ho, Kurt Neo, Keith Weng Kit Leong, Mardiana Marzuki, Bernett Lee, Michael Poidinger, Laura Santambrogio, Liana Tsenova, Francesca Zolezzi, Gennaro De Libero, Amit Singhal, Alessandra Mortellaro

Publications and Research

NLRP10 is a nucleotide-binding oligomerization domain-like receptor that functions as an intracellular pattern recognition receptor for microbial products. Here, we generated a Nlrp10−/− mouse to delineate the role of NLRP10 in the host immune response and found that Nlrp10−/− dendritic cells (DCs) elicited sub-optimal IFNγ production by antigenspecific CD4+ T cells compared to wild-type (WT) DCs. In response to T-cell encounter, CD40 ligation or Toll-like receptor 9 stimulation, Nlrp10−/− DCs produced low levels of IL-12, due to a substantial decrease in NF-κB activation. Defective IL-12 production was also evident in vivo and affected IFNγ production by CD4+ T cells. Upon …


Clinical Risks And Healthcare Utilization Of Hematopoietic Cell Transplantation For Sickle Cell Disease In The Usa Using Merged Databases., Staci D Arnold, Ruta Brazauskas, Naya He, Yimei Li, Richard Aplenc, Zhezhen Jin, Allistair Abraham, +Several Additional Authors Nov 2017

Clinical Risks And Healthcare Utilization Of Hematopoietic Cell Transplantation For Sickle Cell Disease In The Usa Using Merged Databases., Staci D Arnold, Ruta Brazauskas, Naya He, Yimei Li, Richard Aplenc, Zhezhen Jin, Allistair Abraham, +Several Additional Authors

Pediatrics Faculty Publications

Advances in allogeneic hematopoietic cell transplantation for sickle cell disease have improved outcomes, but there is limited analysis of healthcare utilization in this setting. We hypothesized that, compared to late transplantation, early transplantation (at age <10 >years) improves outcomes and decreases healthcare utilization. We performed a retrospective study of children transplanted for sickle cell disease in the USA during 2000-2013 using two large databases. Univariate and Cox models were used to estimate associations of demographics, sickle cell disease severity, and transplant-related variables with mortality and chronic graft-versus-host disease, while Wilcoxon, Kruskal-Wallis, or linear trend tests were applied for the estimates of …


Evolution Of Knowledge, Awareness, And Practices Regarding Zika Virus From 2016 To 2017, Quinton Katler, Prachi Godiwala, Charles J. Macri, Beth Pineles, Gary Simon, Aileen Chang, Homa Ahmadzia Nov 2017

Evolution Of Knowledge, Awareness, And Practices Regarding Zika Virus From 2016 To 2017, Quinton Katler, Prachi Godiwala, Charles J. Macri, Beth Pineles, Gary Simon, Aileen Chang, Homa Ahmadzia

Obstetrics and Gynecology Faculty Publications

Objective. Our team created a knowledge, attitudes, and practice (KAP) survey in order to assess changes over time in healthcare provider and community member awareness of Zika virus symptoms, transmission, treatment, and current and future concerns.

Study Design. The cross-sectional survey was issued at an academic medical center in Washington, DC, and via an online link to healthcare providers and community members between June and August 2016. Survey distribution was then repeated the following year, from March to April 2017. Outcomes were compared by survey year and healthcare provider versus community member status using SAS Program Version 9.4.

Results. Significant …


Knowledge About Asthma: A Cross-Sectional Survey In 4 Major Hospitals Of Karachi, Pakistan, Omar Irfan, Babar Irfan, Zain Ahmad Khan, Maha Tahir, Ali Bin Sarwar Zubairi, Javaid Ahmad Khan Nov 2017

Knowledge About Asthma: A Cross-Sectional Survey In 4 Major Hospitals Of Karachi, Pakistan, Omar Irfan, Babar Irfan, Zain Ahmad Khan, Maha Tahir, Ali Bin Sarwar Zubairi, Javaid Ahmad Khan

Section of Pulmonary & Critical Care

Objective: To determine knowledge and misconceptions about asthma among the local population..Methods: This cross-sectional study was conducted at four tertiary care hospitals; Aga Khan University Hospital, Civil Hospital Karachi, Jinnah Postgraduate Medical Centre and Ojha Institute of Chest Diseases, Karachi, from October to November 2016, and comprised hospital attendants. The questionnaire used in the study comprised 26 questions answered with a true, false or not sure answer.SPSS 20 was used for data analysis.Results: There were 400 participants. The overall mean age was 41.2±14.2 years, and 214(53.5%) of the participants were males. Moreover, 75(19%) participants thought that asthma was a psychological …


Acquired Von Willebrand Disease Associated With Monoclonal Gammopathy Of Unknown Significance, Sijan Basnet, Catherine Lin, Rashmi Dhital, Izza Mir, Elan Mohanty, Biswaraj Tharu, Sushil Ghimire, Dilli Ram Poudel Nov 2017

Acquired Von Willebrand Disease Associated With Monoclonal Gammopathy Of Unknown Significance, Sijan Basnet, Catherine Lin, Rashmi Dhital, Izza Mir, Elan Mohanty, Biswaraj Tharu, Sushil Ghimire, Dilli Ram Poudel

Reading Hospital Internal Medicine Residency

We present a case of a 79-year-old male who presented with retroperitoneal hematoma a week after motor vehicle accident. Prior history and family history of bleeding were nonsignificant. His activated partial thromboplastin time was found to be prolonged in the emergency department. Further workup with coagulation studies showed decreased factor VIII, vWF antigen, and vWF:ristocetin cofactor assay, and negative Bethesda assay, indicating acquired von Willebrand disease. Immunofluorescence to find an underlying etiology was suggestive of MGUS. Management of AvWD depends on controlling active bleeding and treating the underlying cause. He was treated with factor VIII, haemate-p, rituximab, two cycles of …


Multisite Evaluation Of The Bd Max Extended Enteric Bacterial Panel For Detection Of Yersinia Enterocolitica, Enterotoxigenic Escherichia Coli, Vibrio, And Plesiomonas Shigelloides From Stool Specimens., Patricia J Simner, Margret Oethinger, Kathleen A Stellrecht, Dylan R Pillai, Ram Yogev, Helene Leblond, Joel Mortensen Nov 2017

Multisite Evaluation Of The Bd Max Extended Enteric Bacterial Panel For Detection Of Yersinia Enterocolitica, Enterotoxigenic Escherichia Coli, Vibrio, And Plesiomonas Shigelloides From Stool Specimens., Patricia J Simner, Margret Oethinger, Kathleen A Stellrecht, Dylan R Pillai, Ram Yogev, Helene Leblond, Joel Mortensen

Articles, Abstracts, and Reports

The purpose of this study was to perform a multisite evaluation to establish the performance characteristics of the BD Max extended enteric bacterial panel (xEBP) assay directly from unpreserved or Cary-Blair-preserved stool specimens for the detection of Yersinia enterocolitica, enterotoxigenic Escherichia coli (ETEC), Vibrio, and Plesiomonas shigelloides The study included prospective, retrospective, and prepared contrived specimens from 6 clinical sites. BD Max xEBP results were compared to the reference method, which included standard culture techniques coupled with alternate PCR and sequencing, except for ETEC, for which the reference method was two alternate PCRs and sequencing. Alternate PCR was …


Renal Scar Formation And Kidney Function Following Antibiotic-Treated Murine Pyelonephritis., Patrick D. Olson, Lisa K. Mclellan, Alice Liu, Kelleigh L. Briden, Kristin M. Tiemann, Allyssa L. Daugherty, Keith A. Hruska, David A. Hunstad Nov 2017

Renal Scar Formation And Kidney Function Following Antibiotic-Treated Murine Pyelonephritis., Patrick D. Olson, Lisa K. Mclellan, Alice Liu, Kelleigh L. Briden, Kristin M. Tiemann, Allyssa L. Daugherty, Keith A. Hruska, David A. Hunstad

Student Papers, Posters & Projects

We present a new preclinical model to study treatment, resolution and sequelae of severe ascending pyelonephritis. Urinary tract infection (UTI), primarily caused by uropathogenic Escherichia coli (UPEC), is a common disease in children. Severe pyelonephritis is the primary cause of acquired renal scarring in childhood, which may eventually lead to hypertension and chronic kidney disease in a small but important fraction of patients. Preclinical modeling of UTI utilizes almost exclusively females, which (in most mouse strains) exhibit inherent resistance to severe ascending kidney infection; consequently, no existing preclinical model has assessed the consequences of recovery from pyelonephritis following antibiotic treatment. …