Digital Commons Network^™

Understanding The Hygiene Hypothesis And Its Mechanisms, Yaakov Tropper

The Science Journal of the Lander College of Arts and Sciences

The hygiene hypothesis provides an explanation for the sharp increase in atopy over the past several decades by proposing that it is inversely related to the lack of infectious diseases in our society. Although atopy, as well as other hypersensitivity reactions, do have a genetic basis; studies clearly show that environmental and socioeconomic factors play a large role in determining which people will develop allergies. Proposed mechanisms leading to this disorder include an imbalance in the Th1/Th2 complex in the immune system, and a deficiency in Regulatory T cells which controls excessive T cell activity.

A Closer Look: Deep South Has The Highest Hiv-Related Death Rates In The United States, Susan S. Reif, Donna Safley, Carolyn Mcallaster

Faculty Scholarship

No abstract provided.

Opportunities To Improve Postpartum Care For Mothers And Infants: Design Of Context-Specific Packages Of Postpartum Interventions In Rural Districts In Four Sub-Saharan African Countries, Els Duysburgh, Birgit Kerstens, Seni Kouanda, Charles Paulin Kaboré, Danielle Belemsaga Yugbare, Peter Gichangi, Gibson Masache, Beatrice Crahay, Gilda Gondola Sitefane, Nafissa Bique Osman, Severiano Foia, Henrique Barros, Sofia Castro Lopes, Susan Mann, Bejoy Nambiar, Tim Colbourn, Marleen Temmerman

Obstetrics and Gynaecology, East Africa

Background: Postpartum maternal and infant mortality is high in sub-Saharan Africa and improving postpartum care as a strategy to enhance maternal and infant health has been neglected. We describe the design and selection of suitable, context-specific interventions that have the potential to improve postpartum care.

Methods: The study is implemented in rural districts in Burkina Faso, Kenya, Malawi and Mozambique. We used the four steps ‘systems thinking’ approach to design and select interventions: 1) we conducted a stakeholder analysis to identify and convene stakeholders; 2) we organised stakeholders causal analysis workshops in which the local postpartum situation and challenges and …

Mechanisms Of Mitochondrial Dysfunction In Sepsis-Induced Kidney Injury, Joshua Andrew Smith

MUSC Theses and Dissertations

Mitochondrial dysfunction is a well-characterized pathophysiological feature of acute kidney injury (AKI). Our laboratory has previously implicated suppression of mitochondrial biogenesis, the process by which cells generate new and functional mitochondria, as an important contributor to development of mitochondrial dysfunction in multiple experimental models of AKI. However, relatively little is known about the molecular mechanisms responsible for disruption of biogenesis in renal cells. The primary goals of this project were to define signaling pathways mediating acute suppression of renal cortical mitochondrial biogenesis and to characterize changes in glycolytic metabolism that might support both cellular and organ function following sepsis-induced AKI. …

The Balanced Counseling Strategy Plus: A Toolkit For Family Planning Service Providers Working In High Hiv/Sti Prevalence Settings (With Zika Information), Population Council

Reproductive Health

The Balanced Counseling Strategy Plus (BCS+) toolkit, developed and tested in Kenya and South Africa, provides information and materials that healthcare providers need to offer complete, high-quality family planning counseling to clients living in areas with high rates of HIV and STIs. Content is in accordance with the 2015 WHO Medical Eligibility Criteria. The BCS+ provides evidence on clinical indications for the provision of family planning methods, counseling cards, instructions for providers, and guidance for supplemental counseling and services that family planning clients may need. This publication is the English language version with Zika information of the user's guide, trainer's …

Uchunguzi (Journal Watch/Montre De Journal) June 2015, Benjamin Wachira

Internal Medicine, East Africa

Uchunguzi means investigation in Swahili and provides a summary of some of the most recent international literature as presented in other leading journals, but with an emphasis on what is relevant to our continent.

Adipocyte-Induced Inflammation In Prostate Tumor Progression In Bone: Role Of Cxcr2 And Osteopontin, Aimalie Lynnette Hardaway

Wayne State University Dissertations

Abstract

Prostate cancer (PCa) is the second leading cause of cancer-related deaths among men. Evidence suggests that age and obesity, conditions associated with adipocyte accumulation in the bone marrow, are linked to increased risk of developing PCa and progressing to metastatic disease. Studies presented in this dissertation were based on the hypothesis that metastatic progression in bone is a result of a cooperative effort between bone marrow adipocytes, macrophages, osteoclasts, and PCa cells. We specifically focused on two adipocyte-supplied chemokines, CXCL1 and CXCL2, and bone marrow macrophage-secreted osteopontin as key drivers of pro-inflammatory environment in the bone marrow and important …

Characterization Of Cd8+ T Cell Differentiation Following Sivδnef Vaccination By Transcription Factor Expression Profiling, James M. Billingsley, Premeela A. Rajakumar, Michelle A. Connole, Nadine C. Salisch, Sama Adnan, Yury V. Kuzmichev, Henoch S. Hong, R. Keith Reeves, Hyung-Joo Kang, Wenjun Li, Qingsheng Li, Ashley T. Haase, R. Paul Johnson

Nebraska Center for Virology: Faculty Publications

The onset of protective immunity against pathogenic SIV challenge in SIVΔnef-vaccinated macaques is delayed for 15-20 weeks, a process that is related to qualitative changes in CD8⁺ T cell responses induced by SIVΔnef. As a novel approach to characterize cell differentiation following vaccination, we used multi-target qPCR to measure transcription factor expression in naïve and memory subsets of CD8+⁺ T cells, and in SIV-specific CD8⁺ T cells obtained from SIVΔnef-vaccinated or wild type SIVmac239-infected macaques. Unsupervised clustering of expression profiles organized naïve and memory CD8⁺ T cells into groups concordant with cell surface phenotype. Transcription factor …

Escherichia Coli Surface Display Of Single-Chain Antibody Vrc01 Against Hiv-1 Infection, Lin-Xu Wang, Michael Mellon, Dane Bowder, Meghan Quinn, Danielle Shea, Charles Wood, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

Human immunodeficiency virus type 1 (HIV-1) transmission and infection occur mainly via the mucosal surfaces. The commensal bacteria residing in these surfaces can potentially be employed as a vehicle for delivering inhibitors to prevent HIV-1 infection. In this study, we have employed a bacteria-based strategy to display a broadly neutralizing antibody VRC01, which could potentially be used to prevent HIV-1 infection. The VRC01 antibody mimics CD4-binding to gp120 and has broadly neutralization activities against HIV-1. We have designed a construct that can express the fusion peptide of the scFv-VRC01 antibody together with the autotransporter β-barrel domain of IgAP gene from …

Evidence For Placental Hpv Infection In Both Hiv Positive And Negative Women, Chrispin Chisanga, Dawn Eggert, Charles D. Mitchell, Charles Wood, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

Human papillomaviruses (HPVs) have previously been reported to infect epithelial trophoblast cells of the placenta. To investigate this possibility, 200 placental samples from Zambian women were separated into HIV+ and HIV− groups and tested for HPV by redundant primer PCR, using GP5+/GP6+ and CPI/CPII primer sets. Three HPV genotypes (HPV6, 16 and 90) were detected in placental samples. Whereas, 20 different HPV genotypes were detected in vaginal sampling of the same patients, suggesting that compartment specific sub-populations of HPV may exist. The incidence of HPV16 in placental samples was almost 2-fold greater in HIV+ women compared to HIV− (p = …

The Hippo/Yap Pathway Interacts With Egfr Signaling And Hpv Oncoproteins To Regulate Cervical Cancer Progression, Chunbo He, Dagan Mao, Guohua Hua, Xiangmin Lv, Xingcheng Chen, Peter C. Angeletti, Jixin Dong, Steven W. Remmenga, Kerry J. Rodabaugh, Jin Zhou, Paul F. Lambert, Peixin Yang, John S. Davis, Cheng Wang

Nebraska Center for Virology: Faculty Publications

The Hippo signaling pathway controls organ size and tumorigenesis

through a kinase cascade that inactivates Yes-associated

protein (YAP). Here, we show that YAP plays a central role in

controlling the progression of cervical cancer. Our results suggest

that YAP expression is associated with a poor prognosis for cervical

cancer. TGF-α and amphiregulin (AREG), via EGFR, inhibit the Hippo

signaling pathway and activate YAP to induce cervical cancer cell

proliferation and migration. Activated YAP allows for up-regulation

of TGF-α, AREG, and EGFR, forming a positive signaling loop to

drive cervical cancer cell proliferation. HPV E6 protein, a major

etiological molecule of …

Kaposi’S Sarcoma At The University Teaching Hospital, Lusaka, Zambia In The Antiretroviral Therapy Era, Owen Ngalamika, Veenu Minhas, Charles Wood

Nebraska Center for Virology: Faculty Publications

With great interest, we read the recent publication “Kaposi’s sarcoma in HIV-infected patients in South Africa: Multicohort study in the antiretroviral therapy era” by Bohlius et al. We congratulate the authors for their contribution to this field. In this study the authors observed a decrease in incidence of Kaposi’s sarcoma (KS) in patients treated with anti-retroviral therapy (ART) when compared to patients who are not on ART. These results are encouraging because of the ongoing HIV epidemic in sub-Saharan Africa where KS is still one of the most prevalent cancers. Also, it is a relevant topic to study in …

Activation And Degradation Of Open Reading Frame 45 By The Replication And Transcription Activator Of Kaposi's Sarcoma-Associated Herpesvirus, Ying Wang, Kai Yu, Xiuzhi Pei, Tiancheng Zhang, Yuying Guo, Charles Wood, Jinzhong Wang

Nebraska Center for Virology: Faculty Publications

The open reading frame 45 (ORF45) of the Kaposi's sarcoma-associated herpesvirus (KSHV) is an immediate-early phosphorylated tegument protein critical for viral escape from host immune surveillance. Its expression is upregulated by the viral replication and transcription activator (RTA), a key protein that controls the switch from latency to lytic replication. We report here that ORF45 expression was not only upregulated by RTA, but ORF45 could also be degraded by RTA in a proteasome-dependent manner. The ORF45 was activated by RTA via activation of the ORF45 promoter, and the promoter region from nt 69 271 to nt 69 026 was involved. …

Single-Dose Cpg Immunization Protects Against A Heterosubtypic Challenge And Generates Antigen-Specific Memory T Cells, Alexander J. Vogel, Deborah M. Brown

Nebraska Center for Virology: Faculty Publications

Despite extensive research, influenza A virus (IAV) remains a major cause of morbidity, mortality, and healthcare expenditure. Emerging pandemics from highly pathogenic IAV strains, such as H5N1 and pandemic H1N1, highlight the need for universal, crossprotective vaccines. Current vaccine formulations generate strain-specific neutralizing antibodies primarily against the outer coat proteins, hemagglutinin and neuraminidase. In contrast to these highly mutable proteins, internal proteins of IAV are more conserved and are a favorable target for developing vaccines that induce strong T cell responses in addition to humoral immunity. Here, we found that intranasal administration with a single dose of CpG and inactivated …

Long-Acting Parenteral Combination Antiretroviral Loaded Nano-Drug Delivery System To Treat Chronic Hiv-1 Infection: A Humanized Mouse Model Study, Subhra Mandal, Guobin Kang, Pavan Kumar Prathipati, Wenjin Fan, Qingsheng Li, Christopher J. Destache

Nebraska Center for Virology: Faculty Publications

Human immunodeficiency virus (HIV) patients are often diagnosed in the chronic stage of HIV/AIDS. Combination antiretroviral therapy (cART) has improved quality of life for HIV-infected patients. Present study describes a novel long-acting parenteral formulation of combination antiretroviral (cARV) loaded nano-drugs for treating chronic HIV-1 (cHIV) in a humanized-BLT (hu-BLT) mice model. The cARV (elvitegravir + tenofovir alafenamide + emtricitabine; EVG + TAF + FTC) drugs (mimicking marketed Genvoy® one-pill for HIV-treatment) were encapsulated in poly (lactic-co-glycolic acid) nanoparticles (NPs). To establish cHIV, hu-BLT mice were intravaginally challenged with HIV-1 and maintained for 15 weeks. Plasma viral load (pVL) was monitored …

Primary Care Providers’ Knowledge And Experience With Pediatric Acute Watery Diarrhea And Hemolytic Uremic Syndrome, Krista Marie Cassel

DNP Projects

The purpose of this capstone is to investigate the potential for hemolytic uremic syndrome (HUS) risk reduction in children through the evaluation of current evidence as well as pediatric primary care providers' knowledge and experience with children at risk for HUS. The goals of this capstone are to 1) evaluate the current literature to determine best practice for prevention of HUS, 2) assess primary care provider knowledge of HUS and experience with children with acute watery, and 3) develop a guideline for the initial management and referral of these children at risk for HUS.

An Evaluation To The Adherence Of A Sepsis Protocol At A Central Kentucky Community Hospital, Somer K. Robinson

DNP Projects

Background: Sepsis is defined as a “systemic response to an active infectious process in the host” and “represents the systemic inflammatory response to the presence of infection” (American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference, 1992, p.865). In 2008, an estimated 727,000 patients were hospitalized with a diagnosis of sepsis, an increase from 326,000 in 2000, or a 55% increase in prevalence over the eight-year period (Hall, Williams, DeFrances, & Golosinskiy, 2011). Early identification of sepsis with early and effective management strategies has been shown to improve patient outcomes and decrease mortality and prevent organ dysfunction (Levy …

Case 213: Primary Spenic Angiosarcoma, John J. Krol, Vera V. Krol, Adrian Dawkins, Halemane S. Ganesh

Radiology Faculty Publications

A 75-year-old woman with a medical history of gastroesophageal reflux disease and type II diabetes presented to the hospital with a 3-month history of gradually worsening headaches, vague upper abdominal pain, and lower back pain. The patient denied fevers, night sweats, contact with sick individuals, occupational exposure to infection, bleeding, immunodeficiency, intravenous drug use, alcohol or tobacco abuse, history of malignancy, family history of genetic disorders, and international travel. Physical examination revealed a skin-colored mass protruding from the right side of her forehead, but there were no other notable abnormalities. Her diabetes was managed with diet, and the only prescription …

The Perceptions Of The Preparedness Of Medical Graduates To Take On Internship Responsibilities In Low Resource Hospitals In Kenya, Patricia Muthaura, Tashmin Khamis

Obstetrics and Gynaecology, East Africa

The Aga Khan University is developing an Undergraduate Medical Education (UGME) curriculum for implementation in East Africa in 2016, which aims to serve the health needs of the populations there. Pilot focus group discussions of recent interns were conducted at the Aga Khan University Hospital, Nairobi to find out: (1) If Kenyan medical students are adequately prepared for their roles as interns in low resource hospitals upon graduation from medical schools; (2) The likely clinical conditions that interns will face in low resource hospitals in Kenya; and (3) How might the UGME curriculum best prepare interns for their roles in …

Restraint Stress Alters Pro-Inflammatory Cytokine Expression And Increases Superoxide Dismutase In The Rat Hypothalamus And Hippocampus, Kristina Isabel Barron

Open Access Theses & Dissertations

The impact of restraint stress on changes in cytokine expression and oxidative stress markers in hippocampal (Hipp) and hypothalamic (Hyp) regions of the brain, were assessed in a rat model. In addition, immune and inflammatory variables were assessed in peripheral blood. Male Wistar rats were acutely (30 min) or repeatedly (30 min/d for 14 consecutive days) exposed to a restraint stress, or maintained as non-stressed controls. At the time of sacrifice, whole blood and brain tissues enriched in Hyp or Hipp regions were collected; blood was collected with EDTA as an anticoagulant and centrifuged to yield plasma. All tissue samples …

Serine Palmitoyltransferase And Giardial Encystation, Monica Delgado

Open Access Theses & Dissertations

Giardia lamblia is a flagellated protozoan parasite responsible for chronic diarrheal disease in humans and animals. Giardia has minimal lipid synThesis machinery and the majority of its lipids are obtained from the small intestine of humans where the trophozoites colonize. Recent results from our laboratory indicate that sphingolipids (SLs) are also important for Giardia and they regulate encystation and cyst production. Only five SL genes are present in this parasite and they are differentially regulated during encystation. In my studies, I found that giardial serine palmitoyltransferase (gSPT) activity is upregulated in encysting cells, suggesting it might play an important role …

Abdominal Lymphonodular Cryptococcosis In An Immunocompetent Child, Mehjabeen Zaidi, Sonia Qureshi, Sadia Shakoor, Saira Fatima, Fatima Mir

Department of Paediatrics and Child Health

We describe our experience with an apparently immunocompetent child presenting with pyrexia of unknown origin without focal signs. Investigations revealed lymphadenopathy at lung hila, mesentery, and porta hepatis. The child had received at least two months of empiric antituberculous therapy (ATT) before she came to us. A CT-guided biopsy revealed granulomatous inflammation. PAS stain showed yeasts which stained blue with Alcian blue, suggesting C. neoformans.

Impact Of Withholding Breastfeeding At The Time Of Vaccination On The Immunogenicity Of Oral Rotavirus Vaccine--A Randomized Trial, Asad Ali, Abdul Momin Kazi, Margaret M. Cortese, Jessica A. Fleming, Sungsil Moon, Umesh D. Parashar, Baoming Jiang, Monica M. Mcneal, Duncan Steele, Zulfiqar Bhutta

Department of Paediatrics and Child Health

Background: Breast milk contains anti-rotavirus IgA antibodies and other innate immune factors that inhibit rotavirus replication in vitro. These factors could diminish the immunogenicity of oral rotavirus vaccines, particularly if breastfeeding occurs close to the time of vaccine administration.
Methods: Between April 2011 and November 2012, we conducted an open label, randomized trial to compare the immunogenicity of Rotarix (RV1) in infants whose breastfeeding was withheld one hour before through one hour after vaccination with that in infants breastfed at the time of vaccination. The trial was conducted in the peri-urban area of Ibrahim Hyderi in Karachi, Pakistan. Both groups …

Frequency And Mortality Associated With Hyperglycemia In Critically Ill Children, Sabeen Abid Khan, Mohsina Noor Ibrahim, Anwarul Haque

Department of Paediatrics and Child Health

Objective: To determine the frequency of hyperglycemia in critically ill children admitted in PICU of a tertiary care hospital of Karachi and to compare the mortality of critically ill children with and without hyperglycemia.

Study Design: Cross-sectional study.

Place and Duration of Study: Paediatrics Intensive Care Unit (PICU) of National Institute of Child Health (NICH), Karachi, from November 2011 to April 2012.

Methodology: One hundred fifty critically ill children admitted to PICU were included. Patients who had fasting blood sugar levels more than 126 mg/dl within 48 hours of admission were included in the hyperglycemic group. The normoglycemic and hyperglycemic …

Utilization Of Anc And Pnc Services In Nepal : A Multivariate Analysis Based On Nepal Demographic Health Survey 2001 And 2006, Gehendra Mahara, Collins Asweto, Kai Cao, Ali M. Alzain, Andrea Sebastian, Jill Barr, Xiuhua Guo, Wei Wang

Research outputs 2014 to 2021

Background: Maternal Mortality is a public health problem in Nepal, which was highest in 1990 among the South Asian countries. Associated factors of maternal mortality are various; among them maternal health sevices such as antenatal (ANC) and postnatal care (PNC) services are the main. Methods: A multivariate secondary data analysis out based on Nepal Demographic Health Surveys 2001 and 2006. Logistic regression models was performed to compare the utilization of the ANC and PNC services, with background characteristics of women aged between 15 to 49 years old. Results: A total of 8913 reproductive aged groups (15-49) women were taken f …

Developing Local Guidelines For Management Of Sepsis In Adults: Sepsis Guidelines For Pakistan (Sgp), Madiha Hashmi, Fazal Hameed Khan, Sarwar Zubairi, S. Tipu Sultan, Saeeda Haider, Sadqa Aftab, Javed Husain, Anwar Ul Haq, Zahid Akhtar Rao, Amin Khuwaja, Syed Farjad Sultan, Zunairah Rais, Roohina Baloch, Naseem Salahuddin, Aslam Khan, Faisal Sultan, Kamran Chima, Amjad Ali, Gohar Ali

Department of Anaesthesia

Background: The purpose of developing ‘Sepsis Guidelines for Pakistan’ (SGP) is to provide clinicians practicing in local hospitals with a framework to aid timely recognition and management of adult patients in sepsis by adopting evidence-based recommendations of Surviving Sepsis Campaign (SSC) tailored to available resources. These recommendations are not meant to replace the SSC Guidelines.
Methodology: SGP is an initiative of Pakistan Society of Critical Care Medicine (PSCCM). Four key decision points to be addressed in the guidelines were identified by a thirteen member multidisciplinary committee i.e., grading the hospitals in the country, recognition of sepsis and associated organ dysfunction, …

Saccharomyces Boulardii And Bismuth Subsalicylate As Low-Cost Interventions To Reduce The Duration And Severity Of Cholera, Johnathan Sheele, Jessica Cartowski, Angela Dart, Arjun Poddar, Shikha Gupta, Ajay Gupta

Computer Science Faculty Publications

We conducted a randomised single-blinded clinical trial of 100 cholera patients in Port-au-Prince, Haiti to determine if the probiotic Saccharomyces cerevisiae var. boulardii and the anti-diarrhoeal drug bismuth subsalicylate (BS) were able to reduce the duration and severity of cholera. Subjects received either: S. boulardii 250 mg, S. boulardii 250 mg capsule plus BS 524 mg tablet, BS 524 mg, or two placebo capsules every 6 hours alongside standard treatment for cholera. The length of hospitalisation plus the number and volume of emesis, stool and urine were recorded every 6 hours until the study subject was discharged (n=83), left against …

Mcl1 Enhances The Survival Of Cd8+ Memory T Cells After Viral Infection, Jingang Gui, Zhuting Hu, Ching-Yi Tsai, Tian Ma, Yan Song, Amanda Morales, Li-Hao Huang, Ethan Dmitrovsky, Ruth Craig, Edward Usherwood

Dartmouth Scholarship

Viral infection results in the generation of massive numbers of activated effector CD8+ T cells that recognize viral components. Most of these are short-lived effector T cells (SLECs) that die after clearance of the virus. However, a small proportion of this population survives and forms antigen-specific memory precursor effector cells (MPECs), which ultimately develop into memory cells. These can participate in a recall response upon reexposure to antigen even at protracted times postinfection. Here, antiapoptotic myeloid cell leukemia 1 (MCL1) was found to prolong survival upon T cell stimulation, and mice expressing human MCL1 as a transgene exhibited a skewing …

A Coding Variant In Tmc8 (Ever2) Is Associated With High Risk Hpv Infection And Head And Neck Cancer Risk, Caihua Liang, Karl T. Kelsey, Michael D. Mcclean, Brock C. Christensen, Carmen J. Marsit

Dartmouth Scholarship

HPV infection is a causal agent in many epithelial cancers, yet our understanding of genetic susceptibility to HPV infection and resultant cancer risk is limited. Epidermodysplasia Verruciformis is a rare condition of extreme susceptibility to cutaneous HPV infection primarily attributable to mutations in TMC6 and TMC8. Genetic variation in the TMC6/TMC8 region has been linked to beta-type HPV infection and squamous cell carcinoma of the skin, cervical cancer, HPV persistence and progression to cervical cancer. Here, we have tested the hypothesis that the common TMC8 SNP rs7208422 is associated with high-risk HPV infection and risk of head and neck …

Best Practices For Improving Flow And Care Of Pediatric Patients In The Emergency Department., Isabel Barata, Kathleen M. Brown, Laura Fitzmaurice, Elizabeth Stone Griffin, Sally K. Snow, American College Of Emergency Physicians Pediatric Emergency Medicine Committee, Emergency Nurses Association Pediatric Committee, Gregory P. Conners, American Academy Of Pediatrics Committee On Pediatric Emergency Medicine

Manuscripts, Articles, Book Chapters and Other Papers

This report provides a summary of best practices for improving flow, reducing waiting times, and improving the quality of care of pediatric patients in the emergency department.