Anatomy Commons^™

The Implications Of Ferroptosis In Antibiotic Resistance, Marysol Hohl

Senior Honors Theses

Bacterial infections in the United States are becoming increasingly resistant to existing antibiotic treatments. Due to projected increases in resistance and the recent decrease in novel antibacterials, experts have determined that the United States is in the “post-antibiotic era.” The scientific community has failed to resolve resistance despite the continual discovery of new antibiotic compounds. In the past decade, a novel form of cell death called ferroptosis has been implicated in antibiotic treatment by employing the use of nanotechnology. This literature review will describe the problem of bacterial resistance and demonstrate how current research is pioneering a new age of …

Case Report: Cavitary Pneumonia In A 28 Year Old Male, Dan Zaayenga, Katelyn Courtney

Rowan-Virtua Research Day

Cavitary pneumonia can be caused by several different mechanisms. Such causes include suppurative necrosis (pyogenic lung abscess), caseous necrosis (tuberculosis), ischemic necrosis (pulmonary infarction) cystic dilatation of lung structures (ball value obstruction and Pneumocystis pneumonia) as well as malignant processes. Causes are subject to both environmental factors and host susceptibility. The most common cause of infectious process is tuberculosis with its propensity to cause extensive caseous necrosis. The potential for secondary infection after an individual develops a cavitary pneumonia is also great as it provides a shelter for various pathogens the flourish in an environment otherwise usually well-guarded by host …

Biorisk Management, Laboratory Acquired Infections And Clinical Containment, Kashif Ali, Furqan Kabir, Esmeralda Meyer

Department of Paediatrics and Child Health

No abstract provided.

Emergence Of A Multidrug-Resistant And Virulent Streptococcus Pneumoniae Lineage Mediates Serotype Replacement After Pcv13: An International Whole-Genome Sequencing Study, Stephanie W. Lo, Kate Mellor, Robert Cohen, Alba Redin Alonso, Sophie Belman, Narender Kumar, Paulina A. Hawkins, Rebecca A. Gladstone, Sadia Shakoor, Muhammad Imran Nisar

Department of Pathology and Laboratory Medicine

Background: Serotype 24F is one of the emerging pneumococcal serotypes after the introduction of pneumococcal conjugate vaccine (PCV). We aimed to identify lineages driving the increase of serotype 24F in France and place these findings into a global context.
Methods: Whole-genome sequencing was performed on a collection of serotype 24F pneumococci from asymptomatic colonisation (n=229) and invasive disease (n=190) isolates among individuals younger than 18 years in France, from 2003 to 2018. To provide a global context, we included an additional collection of 24F isolates in the Global Pneumococcal Sequencing (GPS) project database for analysis. A Global Pneumococcal Sequence Cluster …

Multiplex Pcr Assay To Detect High Risk Lineages Of Salmonella Typhi And Paratyphi A, Fahad Khokhar, Derek Pickard, Zoe Dyson, Junaid Iqbal, Agila Pragasam, Jobin Jacob John, Balaji Veeraraghavan, Farah Qamar, Gordon Dougan, Hilary Macqueen

Department of Paediatrics and Child Health

Enteric fever infections remain a significant public health issue, with up to 20 million infections per year. Increasing rates of antibiotic resistant strains have rendered many first-line antibiotics potentially ineffective. Genotype 4.3.1 (H58) is the main circulating lineage of S. Typhi in many South Asian countries and is associated with high levels of antibiotic resistance. The emergence and spread of extensively drug resistant (XDR) typhoid strains has increased the need for a rapid molecular test to identify and track these high-risk lineages for surveillance and vaccine prioritisation. Current methods require samples to be cultured for several days, followed by DNA …

Real-World Third Covid-19 Vaccine Dosing And Antibody Response In Patients With Hematologic Malignancies, Michael A. Thompson, Sigrun Hallmeyer, Veronica E. Fitzpatrick, Yunqi Liao, Michael P. Mullane, Stephen C. Medlin, Kenneth Copeland, James L. Weese

Journal of Patient-Centered Research and Reviews

Purpose: This study sought to describe the changes in immune response to a third dose of either Pfizer’s or Moderna’s COVID-19 mRNA vaccine (3V) among patients with hematologic malignancies, as well as associated characteristics

Methods: This retrospective cohort study analyzed pre-3V and post-3V data on 493 patients diagnosed with hematologic malignancies across a large Midwestern health system between August 28, 2021, and November 1, 2021. For antibody testing, S1 spike antigen of the SARS-CoV-2 virus titer was used to determine serostatus.

Results: Among 493 participants, 274 (55.6%) were seropositive both pre- and post-3V (+/+) while 115 (23.3%) seroconverted to positive …

Burden, Clinical Characteristics, Risk Factors, And Seasonality Of Adenovirus 40/41 Diarrhea In Children In Eight Low-Resource Settings, Godfrey Guga, Sarah Elwood, Caroline Kimathi, Gagandeep Kang, Margaret N. Kosek, Aldo A M Lima, Pascal O. Bessong, Amidou Samie, Najeeha Talat Iqbal, Zulfiqar Ahmed Bhutta

Department of Biological & Biomedical Sciences

Background: The application of molecular diagnostics has identified enteric group adenovirus serotypes 40 and 41 as important causes of diarrhea in children. However, many aspects of the epidemiology of adenovirus 40/41 diarrhea have not been described.
Methods: We used data from the 8-site Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project birth cohort study to describe site- and age-specific incidence, risk factors, clinical characteristics, and seasonality.
Results: The incidence of adenovirus 40/41 diarrhea was substantially higher by quantitative polymerase chain reaction than enzyme immunoassay and peaked at ∼30 episodes …

Outcomes Of Covid-19 Infection In Patients With Hematological Malignancies- A Multicenter Analysis From Pakistan, Adeeba Zaki, Salman Muhammad Soomar, Danish Hasan Khan, Hasan Shaharyar Sheikh, Raheel Iftikhar, Ayaz Mir, Zeba Aziz, Khadija Bano, Hafsa Naseer, Qamar Un-Nisa Chaudhry

Section of Haematology/Oncology

Purpose: COVID-19 infection resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began to spread across the globe in early 2020. Patients with hematologic malignancies are supposed to have an increased risk of mortality from coronavirus disease of 2019 (COVID-19) infection. From Pakistan, we report the analysis of the outcome and interaction between patient demographics and tumor subtype and COVID-19 infection and hematological malignancy.
Patients and methods: This multicenter, retrospective study included adult patients with a history of histologically proven hematological malignancies who were tested positive for COVID-19 via PCR presented at the oncology department of 5 tertiary care hospitals …

Anakinra Treatment Efficacy In Reduction Of Inflammatory Biomarkers In Covid-19 Patients: A Meta-Analysis, Zunaira Naveed, Musharraf Sarwar, Zahid Ali, Danish Saeed, Khadija Choudhry, Azza Sarfraz, Zouina Sarfraz, Miguel Felix, Ivan Cherrez-Ojeda

Department of Paediatrics and Child Health

Introduction: Anakinra is being empirically considered for the treatment of COVID-19 patients. The aim is to assess the efficacy of anakinra treatment on inflammatory marker reduction, including c-reactive protein (CRP) concentrations, serum ferritin, and serum d-dimer levels.
Methods: Adhering to PRISMA 2020 statement guidelines, a systematic search was conducted across the following databases from December 2019 until January 10, 2022: PubMed/MEDLINE, Cochrane Central, Web of Science, Scopus, and EMBASE. The following keywords were employed: Anakinra, COVID*, SARS-CoV-2, inflammatory, CRP, D-dimer, Ferritin, hematological, laboratory, clinical, trials. The findings were collated and presented in a tabulated manner, and statistically analyzed using Review …

Characterisation Of Drug-Resistant Mycobacterium Tuberculosis Mutations And Transmission In Pakistan, Gary Napier, Anwar Sheed Khan, Abdul Jabbar, Muhammad Tahir Khan, Sajid Ali, Muhammad Qasim, Noor Mohammad, Rumina Hasan, Zahra Hasan, Susana Campino

Department of Pathology and Laboratory Medicine

Tuberculosis, caused by Mycobacterium tuberculosis, is a high-burden disease in Pakistan, with multi-drug (MDR) and extensive-drug (XDR) resistance, complicating infection control. Whole genome sequencing (WGS) of M. tuberculosis is being used to infer lineages (strain-types), drug resistance mutations, and transmission patterns-all informing infection control and clinical decision making. Here we analyse WGS data on 535 M. tuberculosis isolates sourced across Pakistan between years 2003 and 2020, to understand the circulating strain-types and mutations related to 12 anti-TB drugs, as well as identify transmission clusters. Most isolates belonged to lineage 3 (n = 397; 74.2%) strain-types, and were MDR (n = …

Protocol For A Cluster Randomised Controlled Trial Of Secondary Distribution Of Hepatitis C Self-Testing Within The Context Of A House-To-House Hepatitis C Micro-Elimination Programme In Karachi, Pakistan, Sonjelle Shilton, Dania Ali, Alyia Hasnain, Adeel Abid, Jessica Markby, Muhammad S. Jamil, Niklas Luhmann, Pamela Nabeta, Stefano Ongarello, Saeed Hamid

Medical College Documents

Background: Globally, just 21% of the estimated 58 million people living with hepatitis C virus (HCV) know their status. Thus, there is considerable need to scale-up HCV testing if the World Health Organization (WHO) 2030 hepatitis elimination goals are to be achieved. HCV self-testing may assist with this; however, there are currently no data on the real-world impact of HCV self-testing. With an estimated 5% of the general population living with HCV, Pakistan has the second highest HCV burden in the world. This study aims to evaluate the acceptability and impact of home delivery of HCV self-testing for secondary distribution …

Post-Intensive Care Syndrome Prevention And Detection In Covid-19 Patients, Bethany Sloane Melega

Student Scholar Showcase

COVID-19 has impacts on patient health beyond the hospital. The trauma that patients, and families of patients, can experience during an admission to an intensive care unit (ICU) can last long after discharge from the ICU and the hospital in general. The psychological and physical impacts of ICU hospitalization can cause patients to experience Post Intensive Care Syndrome (PICS). PICS is the culmination of symptoms that persist after a critical illness that involve all aspects of a patient’s physical and mental well-being and can significantly affect family life and increase recovery time. Due to the strict personal-protective equipment (PPE) usage …

A Streptococcus Pneumoniae Lineage Usually Associated With Pneumococcal Conjugate Vaccine (Pcv) Serotypes Is The Most Common Cause Of Serotype 35b Invasive Disease In South Africa, Following Routine Use Of Pcv, Kedibone M. Ndlangisa, Mignon Du Plessis, Stephani Lo, Linda De Gouveia, Chrispin Chaguza, Martin Antonio, Brenda Kwambana-Adams, Jennifer Cornick, Dean B. Everett, Sadia Shakoor

Department of Pathology and Laboratory Medicine

Pneumococcal serotype 35B is an important non-conjugate vaccine (non-PCV) serotype. Its continued emergence, post-PCV7 in the USA, was associated with expansion of a pre-existing 35B clone (clonal complex [CC] 558) along with post-PCV13 emergence of a non-35B clone previously associated with PCV serotypes (CC156). This study describes lineages circulating among 35B isolates in South Africa before and after PCV introduction. We also compared 35B isolates belonging to a predominant 35B lineage in South Africa (GPSC5), with isolates belonging to the same lineage in other parts of the world. Serotype 35B isolates that caused invasive pneumococcal disease in South Africa in …

Development And Validation Of Standard And Real Patient Gallstone Library Using Fourier Transform Infra-Red Spectroscopy, Lena Jafri, Muhammad Abbas Abid, Humera Asif, Syed Bilal Hashmi, Hafsa Majid, Farooq Ghani, Sibtain Ahmed, Imran Siddiqui, Aysha Habib

Department of Pathology and Laboratory Medicine

Background: Analysis of the constituents of gallstones using various spectroscopic techniques assists in identification of the pathogenesis of gallstones. In the current study, using Fourier Transform Infra-Red (FTIR) Spectroscopy, a Gallstone Standard Library (GSL) and a Gallstone Real Patients' Library (GRPL) were developed and validated for gallstone composition analysis.
Methods: The study was conducted at the Department of Pathology & Laboratory Medicine, Aga Khan University, Pakistan. Pure standards (cholesterol, calcium carbonate, bilirubin and bile salts) and gallstone specimens were analyzed using FTIR Nicolet iS-5 Spectrometer from Thermo Fisher Scientific, USA. Thermo Scientific™ QCheck™ algorithm, embedded within the OMNIC™ software, was …

The Who Global Tuberculosis 2021 Report - Not So Good News And Turning The Tide Back To End Tb, Chakaya Jeremiah, Eskild Petersen, Rebecca Nantanda, Brenda N. Mungai, Giovanni Battista Migliori, Farhana Amanullah, Patrick Lungu, Francine Ntoumi, Nagalingeswaran Kumarasamy

Department of Paediatrics and Child Health

Objective: To review the data presented in the 2021 WHO global TB report and discuss the current constraints in the global response.
Introduction and methods: The WHO global TB reports, consolidate TB data from countries and provide up to date assessment of the global TB epidemic. We reviewed the data presented in the 2021 report.
Results: We noted that the 2021 WHO global TB report presents a rather grim picture on the trajectory of the global epidemic of TB including a stagnation in the annual decline in TB incidence, a decline in TB notifications and an increase in estimated TB …

Lymphoma With Tuberculous Granulomas, Jyoti Mohan Lal, Anila Rashid

Department of Pathology and Laboratory Medicine

Chronic granulomatous inflammation is a common finding in lymphoproliferative disorders (LPDs), but it is important to exclude coexisting mycobacterium tuberculosis (MTB) especially in patients from areas of high endemicity. This case emphasizes the relevance of performing MTB culture on bone marrow exhibiting LPD and concomitant granulomas

Characterization Of Age-Associated Gut Microbial Dysbiosis And Plasma Metabolite Alterations In People Living With Hiv (Plwh)., R. Sighal, Smita Ghare, Vaughn Bryant, Sabina Gautam, Chanakya Charan Tirumala, Andrea Reyes-Vega, Craig J. Mcclain, Ronald Cohen, Varand Govind, R L. Cook, Shirish Barve

Faculty Scholarship

Background: HIV-1 infection and aging are independently associated with gut microbial dysbiosis and neurocognitive impairment. However, the interactive effects of HIV-infection and aging on the development of specific pathogenic features of gut microbial dysbiosis and consequent metabolic abnormalities associated with neurocognitive dysfunction remain largely undetermined and were examined in the present study

Comprehensive Echocardiographic Findings In Critically Ill Covid-19 Patients With Or Without Prior Cardiac Disease, Renuka Jain, Pedro D. Salinas, Stacie Kroboth, Abigail Kaminski, Sarah Roemer, Ana Cristina Perez Moreno, Bijoy K Khandheria

Journal of Patient-Centered Research and Reviews

Purpose: Coronavirus disease 2019 (COVID-19) presents with a spectrum of disease severity, the most serious cases requiring intensive care. Echocardiography is a front-line tool in evaluating cardiovascular complications of COVID-19 in the intensive care unit (ICU); we analyzed transthoracic echocardiograms obtained from this patient population with state-of-the-art ultrasound technology.

Methods: All patients with COVID-19 requiring ICU admission on whom a transthoracic echocardiogram was obtained were included in the study. Focused transthoracic protocols were performed by experienced sonographers. Echocardiographic variables, including speckle-tracking echocardiography, were collected and analyzed. Clinical information was obtained from the electronic medical record. Patients were followed until discharge. …

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

Aurora Gastroenterology Faculty

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 …

Central Nervous System Histoplasmosis: Multicenter Retrospective Study On Clinical Features, Diagnostic Approach And Outcome Of Treatment, Joseph Wheat, Thein Myint, Ying Guo, Phebe Kemmer, Chadi A. Hage, Colin Terry, Marwan M. Azar, James Riddell, Peter Ender, Sharon Chen, Kareem Shehab, Kerry Cleveland, Eden Esguerra, James Johnson, Patty Wright, Vanja Douglas, Pascalis Vergidis, Winnie Ooi, John Baddley, David Bamberger, Raed N. Khairy, Holenarasipur R. Vikram, Elizabeth Jenny-Avital, Geetha Sivasubramanian, Karen Bowlware, Barbara Pahud, Juan Sarria, Townson Tsai, Maha Assi, Satish Mocherla

Internal Medicine Faculty Publications

Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with disseminated histoplasmosis. Most experience has been derived from small single center case series, or case report literature reviews. Therefore, a larger study of central nervous system (CNS) histoplasmosis is needed in order to guide the approach to diagnosis, and treatment.

A convenience sample of 77 patients with histoplasmosis infection of the CNS was evaluated. Data was collected that focused on recognition of infection, diagnostic techniques, and outcomes of treatment.

Twenty nine percent of patients were not immunosuppressed. Histoplasma antigen, or anti-Histoplasma antibodies were detected in the …

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 …

Chat Expression In Chlamydia Muridarum-Infected Female Murine Genital Tract, Hallie Sartain

Undergraduate Honors Theses

Chlamydia trachomatis is the most prevalent agent of bacterial sexually transmitted infections in the world. However, a profuse number of cases are unreported, as the infection is often asymptomatic. Sequelae such as pelvic inflammatory disease, an increased risk of cervical cancer, premature birth, and perinatal infections in pregnant women can occur. Inflammation occurs in the body in response to infection or injury. Although inflammation can lead to some unwanted secondary effects, such as pain, it serves to return the body to homeostasis by restoring injured tissues and eliminating pathogens. One recently identified connection between the central nervous system and the …

Human Metapneumovirus Induces Reorganization Of The Actin Cytoskeleton For Direct Cell-To-Cell Spread, Farah El Najjar, Nicolás Cifuentes-Muñoz, Jing Chen, Haining Zhu, Ursula J. Buchholz, Carole L. Moncman, Rebecca Ellis Dutch

Molecular and Cellular Biochemistry Faculty Publications

Paramyxovirus spread generally involves assembly of individual viral particles which then infect target cells. We show that infection of human bronchial airway cells with human metapneumovirus (HMPV), a recently identified paramyxovirus which causes significant respiratory disease, results in formation of intercellular extensions and extensive networks of branched cell-associated filaments. Formation of these structures is dependent on actin, but not microtubule, polymerization. Interestingly, using a co-culture assay we show that conditions which block regular infection by HMPV particles, including addition of neutralizing antibodies or removal of cell surface heparan sulfate, did not prevent viral spread from infected to new target cells. …

The Role Of Glutaminase And Extracellular Vesicles In Macrophages And Microglia, Beiqing Wu

Theses & Dissertations

Glutamate serves as a crucial excitatory neurotransmitter that is essential for the proper functioning of the brain. However, excess levels of glutamate are neurotoxic and contribute to the pathogenesis of various neurodegenerative diseases, inducing HIV-1 associated neurocognitive disorders (HAND). Glutaminase 1 (GLS1) is an important mitochondrial enzyme responsible for producing glutamate from glutamine. GLS1 is upregulated during HAND and released from mitochondria to cytosol and extracellular space. However, why and how GLS1 is released remains unknown. In chapter II, we demonstrated that extracellular vesicles (EVs) carry GLS1 as cargos from cytosol to extracellular space during HIV infection and innate immune …

Coculture Of Staphylococcus Aureus With Pseudomonas Aeruginosa Drives S. Aureus Towards Fermentative Metabolism And Reduced Viability In A Cystic Fibrosis Model, Laura M. Filkins, Jyoti A. Graber, Daniel G. Olson, Emily L. Dolben, Lee Lynd, Sabin Bhuju, George A. O'Toole

Dartmouth Scholarship

The airways of patients with cystic fibrosis are colonized with diverse bacterial communities that change dynamically during pediatric years and early adulthood. Staphylococcus aureus is the most prevalent pathogen during early childhood, but during late teens and early adulthood, a shift in microbial composition occurs leading to Pseudomonas aeruginosa community predominance in ∼50% of adults. We developed a robust dual-bacterial in vitro coculture system of P. aeruginosa and S. aureus on monolayers of human bronchial epithelial cells homozygous for the ΔF508 cystic fibrosis transmembrane conductance regulator (CFTR) mutation to better model the mechanisms of this interaction. We show that P. …

The Role Of Il-27 In Susceptibility To Post-Influenza Staphylococcus Aureus Pneumonia, Keven M. Robinson, Benjamin Lee, Erich V Scheller, Sivanarayana Mandalapu, Richard I. Enelow

Dartmouth Scholarship

Influenza is a common respiratory virus and Staphylococcus aureus frequently causes secondary pneumonia during influenza infection, leading to increased morbidity and mortality. Influenza has been found to attenuate subsequent Type 17 immunity, enhancing susceptibility to secondary bacterial infections. IL-27 is known to inhibit Type 17 immunity, suggesting a potential critical role for IL-27 in viral and bacterial co-infection.

Cyclooxygenase-2, Prostaglandin E2, And Prostanoid Receptor Ep2 In Fluid Flow Shear Stress-Mediated Injury In The Solitary Kidney., Tarak Srivastava, Uri S. Alon, Patricia A. Cudmore, Belal Tarakji, Alexander Kats, Robert E. Garola, R Scott Duncan, Ellen T. Mccarthy, Ram Sharma, Mark L. Johnson, Lynda F. Bonewald, Ashraf El-Meanawy, Virginia J. Savin, Mukut Sharma

Manuscripts, Articles, Book Chapters and Other Papers

Hyperfiltration subjects podocytes to increased tensile stress and fluid flow shear stress (FFSS). We showed a 1.5- to 2.0-fold increase in FFSS in uninephrectomized animals and altered podocyte actin cytoskeleton and increased synthesis of prostaglandin E2 (PGE2) following in vitro application of FFSS. We hypothesized that increased FFSS mediates cellular changes through specific receptors of PGE2. Presently, we studied the effect of FFSS on cultured podocytes and decapsulated isolated glomeruli in vitro, and on solitary kidney in uninephrectomized sv129 mice. In cultured podocytes, FFSS resulted in increased gene and protein expression of cyclooxygenase (COX)-2 but not COX-1, prostanoid receptor EP2 …

Infective Endocarditis In The U.S., 1998–2009: A Nationwide Study, David H. Bor, Steffie Woolhandler, Rachel Nardin, David Brusch, David U. Himmelstein

Publications and Research

Background
Previous studies based on local case series estimated the annual incidence of endocarditis in the U.S. at about 4 per 100,000 population. Small-scale studies elsewhere have reported similar incidence rates. However, no nationally-representative population-based studies have verified these estimates.

Methods and Findings
Using the 1998–2009 Nationwide Inpatient Sample, which provides diagnoses from about 8 million U.S. hospitalizations annually, we examined endocarditis hospitalizations, bacteriology, co-morbidities, outcomes and costs. Hospital admissions for endocarditis rose from 25,511 in 1998 to 38, 976 in 2009 (12.7 per 100,000 population in 2009). The age-adjusted endocarditis admission rate increased 2.4% annually. The proportion of patients …

Lps And Pan-Induced Podocyte Injury In An In Vitro Model Of Minimal Change Disease: Changes In Tlr Profile., Tarak Srivastava, Mukut Sharma, Kok-Hooi Yew, Ram Sharma, R Scott Duncan, Moin A. Saleem, Ellen T. Mccarthy, Alexander Kats, Patricia A. Cudmore, Uri S. Alon, Christopher J. Harrison

Manuscripts, Articles, Book Chapters and Other Papers

Minimal change disease (MCD), the most common idiopathic nephrotic syndrome in children, is characterized by proteinuria and loss of glomerular visceral epithelial cell (podocyte) ultrastructure. Lipopolysaccharide (LPS) and puromycin aminonucleoside (PAN) are used to study podocyte injury in models of MCD in vivo and in vitro. We hypothesized that LPS and PAN influence components of the innate immune system in podocytes such as the Toll-Like Receptor (TLRs), TLR adapter molecules, and associated cytokines. Our results show that cultured human podocytes constitutively express TLRs 1-6 and TLR-10, but not TLRs 7-9. LPS (25 μg/ml) or PAN (60 μg/ml) caused comparable derangement …

A Double Blind Community-Based Randomized Trial Of Amoxicillin Versus Placebo For Fast Breathing Pneumonia In Children Aged 2-59 Months In Karachi, Pakistan (Retapp), Fyezah Jehan, Muhammad Imran Nisar, Salima Kerai, Nick Brown, Benazir Balouch, Zulfiqar Hyder, Gwen Ambler, Amy Sarah Ginsburg, Anita K. M. Zaidi

Department of Paediatrics and Child Health

Background: Fast breathing pneumonia is characterized by tachypnoea in the absence of danger signs and is mostly viral in etiology. Current guidelines recommend antibiotic therapy for all children with fast breathing pneumonia in resource limited settings, presuming that most pneumonia is bacterial. High quality clinical trial evidence to challenge or support the continued use of antibiotics, as recommended by the World Health Organization is lacking.

Methods/Design: This is a randomized double blinded placebo-controlled non-inferiority trial using parallel assignment with 1:1 allocation ratio, to be conducted in low income squatter settlements of urban Karachi, Pakistan. Children 2-59 months old with fast …