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Suppression Of Chrn Endocytosis By Carbonic Anhydrase Car3 In The Pathogenesis Of Myasthenia Gravis, Ailian Du, Shiqian Huang, Xiaonan Zhao, Kuan Fang, Shuangyan Zhang, Jiefang Huang, Xiang Miao, Fulvio Baggi, Rennolds S. Ostrom, Yanyun Zhang, Xiangjun Chen, Congfeng Xu 2017 Shanghai Jiao Tong University

Suppression Of Chrn Endocytosis By Carbonic Anhydrase Car3 In The Pathogenesis Of Myasthenia Gravis, Ailian Du, Shiqian Huang, Xiaonan Zhao, Kuan Fang, Shuangyan Zhang, Jiefang Huang, Xiang Miao, Fulvio Baggi, Rennolds S. Ostrom, Yanyun Zhang, Xiangjun Chen, Congfeng Xu

Pharmacy Faculty Articles and Research

Myasthenia gravis is an autoimmune disorder of the neuromuscular junction manifested as fatigable muscle weakness, which is typically caused by pathogenic autoantibodies against postsynaptic CHRN/ AChR (cholinergic receptor nicotinic) in the endplate of skeletal muscle. Our previous studies have identified CA3 (carbonic anhydrase 3) as a specific protein insufficient in skeletal muscle from myasthenia gravis patients. In this study, we investigated the underlying mechanism of how CA3 insufficiency might contribute to myasthenia gravis. Using an experimental autoimmune myasthenia gravis animal model and the skeletal muscle cell C2C12, we find that inhibition of CAR3 (the mouse homolog of CA3) promotes CHRN ...


Coxsackievirus-Induced Proteomic Alterations In Primary Human Islets Provide Insights For The Etiology Of Diabetes, Julius O. Nyalwidhe, Glen R. Gallagher, Lindsey M. Glenn, Margaret A. Morris, Pranitha Vangala, Agata Jurczyk, Rita Bortell, David M. Harlan, Jennifer P. Wang, Jerry L. Nadler 2017 Eastern Virginia Medical School

Coxsackievirus-Induced Proteomic Alterations In Primary Human Islets Provide Insights For The Etiology Of Diabetes, Julius O. Nyalwidhe, Glen R. Gallagher, Lindsey M. Glenn, Margaret A. Morris, Pranitha Vangala, Agata Jurczyk, Rita Bortell, David M. Harlan, Jennifer P. Wang, Jerry L. Nadler

Open Access Articles

Enteroviral infections have been associated with the development of type 1 diabetes (T1D), a chronic inflammatory disease characterized by autoimmune destruction of insulin-producing pancreatic beta cells. Cultured human islets, including the insulin-producing beta cells, can be infected with coxsackievirus B4 (CVB4) and thus are useful for understanding cellular responses to infection. We performed quantitative mass spectrometry analysis on cultured primary human islets infected with CVB4 to identify molecules and pathways altered upon infection. Corresponding uninfected controls were included in the study for comparative protein expression analyses. Proteins were significantly and differentially regulated in human islets challenged with virus compared with ...


Impact Of Rituximab On Patient-Reported Outcomes In Patients With Rheumatoid Arthritis From The Us Corrona Registry, Leslie R. Harrold, Ani John, Jennie Best, Steve Zlotnick, Chitra Karki, YouFu Li, Jeffrey D. Greenberg, Joel M. Kremer 2017 University of Massachusetts Medical School

Impact Of Rituximab On Patient-Reported Outcomes In Patients With Rheumatoid Arthritis From The Us Corrona Registry, Leslie R. Harrold, Ani John, Jennie Best, Steve Zlotnick, Chitra Karki, Youfu Li, Jeffrey D. Greenberg, Joel M. Kremer

Open Access Articles

To evaluate the impact of rituximab on patient-reported outcomes (PROs) in a US-based observational cohort of patients with rheumatoid arthritis (RA). Patients with active RA, prior exposure to > /=1 tumor necrosis factor inhibitor (TNFi) and who newly initiated rituximab were identified. Changes in PROs were assessed 1 year after rituximab initiation. PRO measures included Clinical Disease Activity Index (CDAI); patient global disease activity, pain and fatigue (visual analog score; 0-100); morning stiffness (hours); modified Health Assessment Questionnaire (mHAQ; 0-3); and EuroQoL EQ-5D. Of the 667 patients who newly initiated rituximab, baseline PRO and clinical measures indicated that patients were substantially ...


Interventions To Reduce Neonatal Mortality From Neonatal Tetanus In Low And Middle Income Countries - A Systematic Review, Adeel Ahmed Khan, Aysha Zahidie, F. Rabbani 2017 Aga Khan University

Interventions To Reduce Neonatal Mortality From Neonatal Tetanus In Low And Middle Income Countries - A Systematic Review, Adeel Ahmed Khan, Aysha Zahidie, F. Rabbani

Fauziah Rabbani

Background In 1988, WHO estimated around 787,000 newborns deaths due to neonatal tetanus. Despite few success stories majority of the Low and Middle Income Countries (LMICs) are still struggling to reduce neonatal mortality due to neonatal tetanus. We conducted a systematic review to understand the interventions that have had a substantial effect on reducing neonatal mortality rate due to neonatal tetanus in LMICs and come up with feasible recommendations for decreasing neonatal tetanus in the Pakistani setting. Methods We systemically reviewed the published literature (Pubmed and Pubget databases) to identify appropriate interventions for reducing tetanus related neonatal mortality. A ...


Frequency And Predictors Of Self-Reported Hypoglycemia In Insulin-Treated Diabetes, Samir Malkani, Anupam Kotwal 2017 University of Massachusetts Medical School

Frequency And Predictors Of Self-Reported Hypoglycemia In Insulin-Treated Diabetes, Samir Malkani, Anupam Kotwal

Open Access Articles

AIMS: Hypoglycemia is a limiting factor for achieving stringent glycemic control in diabetes. This study analyzes the frequency and predictors of hypoglycemia in insulin-treated diabetes in an ambulatory setting.

METHODS: A retrospective chart review was performed to study self-monitored blood glucose (SMBG) data for 3 months prior to a patient's HbA1c test.

RESULTS: Hypoglycemia occurred more frequently in type 1 than in type 2 diabetes; however, 19% of type 2 diabetes patients did experience at least one episode of severe hypoglycemia. For type 1 diabetes, hypoglycemia had a positive association with glycemic variability and duration of diabetes and a ...


A Roundtable On Cross-Sector Collaboration And Resource Alignment For Health Equity: Meeting Summary, Onyemaechi Nweke 2017 US Department of Health and Human Services

A Roundtable On Cross-Sector Collaboration And Resource Alignment For Health Equity: Meeting Summary, Onyemaechi Nweke

Journal of Health Disparities Research and Practice

Cross-sector collaboration is a highly recommended strategy to eliminate health inequities nationally and globally. In the federal sector, it is evolving into an important approach for solving complex social problems, as evidenced by its steady proliferation the past few decades. Despite the increased adoption of cross-sector collaboration, it is still not a default strategy or preeminent option for managing complex social problems. In September 2015, the Federal Interagency Health Equity Team (FIHET) hosted a Roundtable event to discuss opportunities and strategies to foster widespread adoption of cross-sector collaboration and resource alignment. The Roundtable featured several expert panelists and participants from ...


An Assessment Of Funding And Other Capacity Needs For Health Equity Programming Within State-Level Chronic Disease Programs, Tiffany Pertillar, Ann Pobutsky, PhD, Gail Brandt, EdD, MPH, Marisa New, OTR, MPH, JamieLou Delavan, BA, Robyn Taylor, MBA, Amishi Shah, MPA, MA, Folasaya Adunola, DDS, MPH, Onyemaechi Nweke 2017 National Association of Chronic Disease Directors

An Assessment Of Funding And Other Capacity Needs For Health Equity Programming Within State-Level Chronic Disease Programs, Tiffany Pertillar, Ann Pobutsky, Phd, Gail Brandt, Edd, Mph, Marisa New, Otr, Mph, Jamielou Delavan, Ba, Robyn Taylor, Mba, Amishi Shah, Mpa, Ma, Folasaya Adunola, Dds, Mph, Onyemaechi Nweke

Journal of Health Disparities Research and Practice

Background: Chronic diseases are an important contributor to morbidity and mortality among racial/ethnic minority, low-income, and other under-resourced populations. Given that state health departments (and their chronic disease programs) play a significant role in providing population and preventive health services, their capacity to promote health equity is an important consideration in national efforts to address chronic diseases. The purpose of this study was to examine capacity needs of state chronic disease programs with respect to promoting health equity.

Methods: In 2015, the National Association of Chronic Disease Directors (NACDD) conducted a survey of its members that work within a ...


Achieving Health Equity For Indian Country, Jamie Ishcomer 2017 National Indian Health Board

Achieving Health Equity For Indian Country, Jamie Ishcomer

Journal of Health Disparities Research and Practice

The essence of health equity is giving resources where they are needed most. American Indians and Alaska Natives (AI/AN) continue to have the worst health outcomes, live in some of the most desperate of conditions, and lack access to even basic amenities that many other Americans could not survive without. Although Tribes have been plagued with social, economic and political injustice for centuries, there is an opportunity to put a stop to the systematic oppression and build up the first peoples of this country. A partnership between the National Indian Health Board (NIHB) and the National Partnership for Action ...


Rhode Island’S Health Equity Zones: Addressing Local Problems With Local Solutions, Nicole Alexander-Scott, MD, MPH, Ana P. Novais, MA, Carol Hall-Walker, MPA, Angela B. Ankoma, MPH, MSW, John P. Fulton, PhD 2017 Rhode Island Department of Health

Rhode Island’S Health Equity Zones: Addressing Local Problems With Local Solutions, Nicole Alexander-Scott, Md, Mph, Ana P. Novais, Ma, Carol Hall-Walker, Mpa, Angela B. Ankoma, Mph, Msw, John P. Fulton, Phd

Journal of Health Disparities Research and Practice

The Rhode Island Department of Health (RIDOH) describes the strategies and infrastructure it has developed to fund its placed-based initiatives to address the social determinants of health to eliminate health disparities. Using a data driven and community-led approach, RIDOH funded 10 local collaboratives, each with its own, geographically-defined “Health Equity Zone,” or “HEZ,” and, to support the collaboratives, created a new “Health Equity Institute,” a “HEZ Team” of 9 seasoned project managers, and direct lines of communications between these assets and the Office of the Director of Health.


Implementation Of The National Partnership For Action To End Health Disparities: A Three-Year Retrospective, Oscar Espinosa, Brandon Coffee-Borden, MPP Coffee-Borden, MPP, Alexis Bakos, PhD, MPH, RN, D. Bakos, PhD, MPH, RN, Onyemaechi Nweke 2017 Community Science

Implementation Of The National Partnership For Action To End Health Disparities: A Three-Year Retrospective, Oscar Espinosa, Brandon Coffee-Borden, Mpp Coffee-Borden, Mpp, Alexis Bakos, Phd, Mph, Rn, D. Bakos, Phd, Mph, Rn, Onyemaechi Nweke

Journal of Health Disparities Research and Practice

In April 2011, the U.S. Department of Health and Human Services’ (HHS) Office of Minority Health (OMH) launched the National Partnership for Action to End Health Disparities (NPA) to increase the effectiveness of efforts to eliminate health disparities by coordinating partners, leaders, and stakeholders committed to action. At its core, the NPA is an experiment in collaboration that relies heavily on those on the front line who are actively engaged in minority health work at multiple levels. It gives them the responsibility of identifying and helping to define core actions, new approaches, and new partnerships that ultimately will help ...


The Guide To Community Preventive Services Review Of Interventions To Promote Health Equity In The United States, Robert Hahn, Jonathan E. Fielding, M.D., M.P.H., M.A., M.B.A, Robert L. Johnson, M.D., Carles Muntaner, M.D., Ph.D., M.H.S., Benedict I. Truman, M.D., M.P.H., Tracy Orleans 2017 U.S. Centers for Disease Control and Prevention

The Guide To Community Preventive Services Review Of Interventions To Promote Health Equity In The United States, Robert Hahn, Jonathan E. Fielding, M.D., M.P.H., M.A., M.B.A, Robert L. Johnson, M.D., Carles Muntaner, M.D., Ph.D., M.H.S., Benedict I. Truman, M.D., M.P.H., Tracy Orleans

Journal of Health Disparities Research and Practice

The optimal approach to eliminating health inequities is through evidence-based interventions. In 2009, the non-federal Community Preventive Services Task Force launched a series of systematic reviews of interventions to promote health equity. Topics to be considered include education, employment, housing, and transportation. Thus far, reviews have focused on educational interventions: center-based early childhood education, full-day kindergarten programs, out-of-school time academic programs, high school completion programs, and school-based health centers. These reviews demonstrate the benefits of diverse educational interventions in advancing health equity. Here, we summarize the strategy of Community Guide health equity reviews, first findings and challenges.


Primary Iga And Igg Subclass Deficiency In A 17-Year-Old Pakistani Girl: A Case Report., Taimur Saleem, Madiha Rabbani, Bushra Jamil 2017 Aga Khan University

Primary Iga And Igg Subclass Deficiency In A 17-Year-Old Pakistani Girl: A Case Report., Taimur Saleem, Madiha Rabbani, Bushra Jamil

Bushra Jamil

Primary immunodeficiency disorders pose a diagnostic dilemma for physicians in the developing countries such as Pakistan because of lack of adequate diagnostic facilities. We present here the case of a 17-year-old girl who had a history of recurrent respiratory tract infections since childhood and had been treated with anti-tuberculous medications thrice, for a total of 24 months. She had also received multiple courses of antibiotics. Her initial presentation to our hospital was with acute bronchopneumonia. Her past medical history of recurrent infections also alerted the treating physician to the possibility of bronchiectasis secondary to a variety of underlying potential pathologies ...


Multiple Myeloma Baseline Immunoglobulin G Level And Pneumococcal Vaccination Antibody Response, Michael A. Thompson, Martin K. Oaks, Maharaj Singh, Karen M. Michel, Michael P. Mullane, Husam S. Tarawneh, Angi Kraut, Kayla J. Hamm 2017 Aurora Research Institute / Aurora Cancer Care, Aurora Health Care

Multiple Myeloma Baseline Immunoglobulin G Level And Pneumococcal Vaccination Antibody Response, Michael A. Thompson, Martin K. Oaks, Maharaj Singh, Karen M. Michel, Michael P. Mullane, Husam S. Tarawneh, Angi Kraut, Kayla J. Hamm

Journal of Patient-Centered Research and Reviews

Infections are a major cause of morbidity and mortality in multiple myeloma (MM), a cancer of the immune system. Vaccination clinical efficacy endpoints have not been demonstrated, and there are limited data on surrogate markers of efficacy. This pilot study evaluated sequential immunologic markers after standard pneumococcal vaccination (PV) in patients with MM and non-MM controls. Vaccination was standard for PV (PCV13 or PPV23), with laboratory testing at baseline and at 2, 4, 12 and 24 weeks after vaccination. Immunoglobulin G (IgG) antibodies to pneumococcal antigens were detected by ELISA. Prevaccination total IgG levels and IgG subclass levels were also ...


Human Gut-Derived Commensal Bacteria Suppress Cns Inflammatory And Demyelinating Disease, Ashutosh K Mangalam, Shailesh K Shahi, David Luckey, Melissa Karau, Eric Marietta, Ningling Luo, Rok Seon Choung, Josephine Ju, Ramakrishna Sompallae, Katherine Gibson-Corley, Robin Patel, Moses Rodriguez, Chella David, Veena Taneja, Joseph Murray 2017 University of Iowa

Human Gut-Derived Commensal Bacteria Suppress Cns Inflammatory And Demyelinating Disease, Ashutosh K Mangalam, Shailesh K Shahi, David Luckey, Melissa Karau, Eric Marietta, Ningling Luo, Rok Seon Choung, Josephine Ju, Ramakrishna Sompallae, Katherine Gibson-Corley, Robin Patel, Moses Rodriguez, Chella David, Veena Taneja, Joseph Murray

Department of Pathology Publications

The human gut is colonized by a large number of microorganisms (∼1013 bacteria) that support various physiologic functions. A perturbation in the healthy gut microbiome might lead to the development of inflammatory diseases, such as multiple sclerosis (MS). Therefore, gut commensals might provide promising therapeutic options for treating MS and other diseases. We report the identification of human gut-derived commensal bacteria, Prevotella histicola, which can suppress experimental autoimmune encephalomyelitis (EAE) in a human leukocyte antigen (HLA) class II transgenic mouse model. P. histicola suppresses disease through the modulation of systemic immune responses. P. histicola challenge led to a decrease in ...


Extrafollicular Activities: Perspectives On Hiv Infection, Germinal Centerindependent Maturation Pathways, And Kshv-Mediated Lymphoproliferation, Jennifer Totonchy 2017 Chapman University

Extrafollicular Activities: Perspectives On Hiv Infection, Germinal Centerindependent Maturation Pathways, And Kshv-Mediated Lymphoproliferation, Jennifer Totonchy

Pharmacy Faculty Articles and Research

Early events in the pathogenesis of KSHV-associated lymphoproliferations in the context of HIV disease remain poorly understood. Recent research indicates that latent HIV infection causes persistent immune dysfunction in B cell follicles. Simultaneously, lack of T cell immune surveillance in the lymph nodes dysregulates the biology of EBV. In sum, these defects bias B lymphocyte maturation away from traditional T cell-dependent germinal center-mediated pathways and towards extrafollicular pathways. Recent advances in B lymphocyte immunology suggest that extrafollicular maturation pathways for antibody secreting cells are more flexible and robust than previously believed. These responses are now understood to be both durable ...


Effect Of Ultrasonication On The Physicochemical Properties Of Sorghum Kafirin And Evaluation Of Its Anti-Inflammatory Properties In Vitro, Andrew Cullen Sullivan 2017 University of Tennessee, Knoxville

Effect Of Ultrasonication On The Physicochemical Properties Of Sorghum Kafirin And Evaluation Of Its Anti-Inflammatory Properties In Vitro, Andrew Cullen Sullivan

Masters Theses

Sorghum is one of the hardiest, most drought resistent cereal grains known to exist, providing the bulk of nutritional content for many semi-arid regions and developing countries throughout Africa and southwestern Asia. It contains dense nutritional value, but due to inhibition factors within the grain, much of these nutrients are indigestible. Access to these nutrients, which have shown to contain high contents of bioactive molecules linked to the decrease of prevalence of chronic disease, must then be facilitated before consumption. In sorghum, these molecules could include complex carbohydrates, proteins and polyphenols. The overall objective of this study was to determine ...


Risk For Cardiovascular Disease In Blacks With Hiv/Aids In America: A Systematic Review And Meta-Analysis, Calvin Odhiambo, Jessica Davis, Bernard Omolo 2017 University of South Carolina Upstate

Risk For Cardiovascular Disease In Blacks With Hiv/Aids In America: A Systematic Review And Meta-Analysis, Calvin Odhiambo, Jessica Davis, Bernard Omolo

Journal of Health Disparities Research and Practice

Cardiovascular disease (CVD) related to HIV infection is becoming a major public health concern in the United Stated. Epidemiologic studies show that prolonged use of Highly Active Antiretroviral Therapy, HIV/AIDS itself, and a combination of traditional vascular risk factors increase the risk for CVD among people with HIV/AIDS. However, little is known about any racial disparities in the risk for CVD in the HIV/AIDS population. We conducted a systematic review and meta-analysis of literature on HIV/AIDS and CVD (June 1, 2010-July 31, 2014) through MEDLINE to examine whether and how HIV-positive African Americans are disproportionately affected ...


Germinal Centre Frequency Is Decreased In Pancreatic Lymph Nodes From Individuals With Recent-Onset Type 1 Diabetes, Abby Willcox, Sarah J. Richardson, Lucy S. K. Walker, Sally C. Kent, Noel G. Morgan, Kathleen M. Gillespie 2017 University of Bristol

Germinal Centre Frequency Is Decreased In Pancreatic Lymph Nodes From Individuals With Recent-Onset Type 1 Diabetes, Abby Willcox, Sarah J. Richardson, Lucy S. K. Walker, Sally C. Kent, Noel G. Morgan, Kathleen M. Gillespie

Open Access Articles

AIMS/HYPOTHESIS: Pancreatic lymph nodes (PLNs) are critical sites for the initial interaction between islet autoantigens and autoreactive lymphocytes, but the histology of PLNs in tissue from individuals with type 1 diabetes has not been analysed in detail. The aim of this study was to examine PLN tissue sections from healthy donors compared with those at risk of, or with recent-onset and longer-duration type 1 diabetes.

METHODS: Immunofluorescence staining was used to examine PLN sections from the following donor groups: non-diabetic (n=15), non-diabetic islet autoantibody-positive (n=5), recent-onset ( < /=1.5 years duration) type 1 diabetes (n=13), and longer-duration type 1 diabetes (n=15). Staining for CD3, CD20 and Ki67 was used to detect primary and secondary (germinal centre-containing) follicles and CD21 and CD35 to detect follicular dendritic cell networks.

RESULTS: The frequency of secondary follicles was lower in the recent-onset ...


Possible Type 1 Diabetes Risk Prediction: Using Ultrasound Imaging To Assess Pancreas Inflammation In The Inducible Autoimmune Diabetes Bbdr Model, Frederick R. Roberts, Clinton Hupple, Elaine Norowski, Nicole C. Walsh, Natalia Przewozniak, Ken-Edwin Aryee, Filia M. Van Dessel, Agata Jurczyk, David M. Harlan, Dale L. Greiner, Rita Bortell, Chaoxing Yang 2017 FuJiFilm VisualSonics

Possible Type 1 Diabetes Risk Prediction: Using Ultrasound Imaging To Assess Pancreas Inflammation In The Inducible Autoimmune Diabetes Bbdr Model, Frederick R. Roberts, Clinton Hupple, Elaine Norowski, Nicole C. Walsh, Natalia Przewozniak, Ken-Edwin Aryee, Filia M. Van Dessel, Agata Jurczyk, David M. Harlan, Dale L. Greiner, Rita Bortell, Chaoxing Yang

Open Access Articles

BACKGROUND/AIMS: Studies of human cadaveric pancreas specimens indicate that pancreas inflammation plays an important role in type 1 diabetes pathogenesis. Due to the inaccessibility of pancreas in living patients, imaging technology to visualize pancreas inflammation is much in need. In this study, we investigated the feasibility of utilizing ultrasound imaging to assess pancreas inflammation longitudinally in living rats during the progression leading to type 1 diabetes onset.

METHODS: The virus-inducible BBDR type 1 diabetes rat model was used to systematically investigate pancreas changes that occur prior to and during development of autoimmunity. The nearly 100% diabetes incidence upon virus ...


Immune Checkpoint Inhibition And The Prevalence Of Autoimmune Disorders Among Patients With Lung And Renal Cancer, Sherif M. El-Refai 2017 University of Kentucky

Immune Checkpoint Inhibition And The Prevalence Of Autoimmune Disorders Among Patients With Lung And Renal Cancer, Sherif M. El-Refai

Pharmaceutical Sciences Faculty Publications

PURPOSE: Immune checkpoint inhibition reactivates the immune response against cancer cells in multiple tissue types and has been shown to induce durable responses. However, for patients with autoimmune disorders, their conditions can worsen with this reactivation. We sought to identify, among patients with lung and renal cancer, how many harbor a comorbid autoimmune condition and may be at risk of worsening their condition while on immune checkpoint inhibitors such as nivolumab and pembrolizumab.

METHODS: An administrative health care claims database, Truven MarketScan, was used to identify patients diagnosed with lung and renal cancer from 2010 to 2013. We assessed patients ...


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