Medicine and Health Sciences Commons^™

Bronchopulmonary Dysplasia: Pathophysiology And The Effects Of The Microbiome, Anjali Jacob

Senior Honors Theses

Bronchopulmonary dysplasia (BPD) is a chronic neonatal lung disease that occurs in over 50% of premature infants. BPD is characterized by damage to the alveoli and bronchioles and improper vasculature formation. It is primarily caused by overexposure to oxygen through mechanical ventilation, but there are other risk factors that make infants more susceptible to BPD. Microbial composition impacts risk for developing BPD, and research is ongoing about the effects of the microbiome on BPD pathogenesis; this information is also valuable for preventative treatment. This paper reviews the normal function of the lungs, pathogenesis of BPD and how it affects normal …

Interplay Between Acetylation And Ubiquitination Of Imitation Switch Chromatin Remodeler Isw1 Confers Multidrug Resistance In Cryptococcus Neoformans, Yang Meng, Yue Ni, Zhuoran Li, Tianhang Jiang, Tianshu Sun, Yanjian Li, Xindi Gao, Hailong Li, Chenhao Suo, Chao Li, Sheng Yang, Tian Lan, Guojian Liao, Tongbao Liu, Ping Wang, Chen Ding

School of Medicine Faculty Publications

Cryptococcus neoformans poses a threat to human health, but anticryptococcal therapy is hampered by the emergence of drug resistance, whose underlying mechanisms remain poorly understood. Herein, we discovered that Isw1, an imitation switch chromatin remodeling ATPase, functions as a master modulator of genes responsible for in vivo and in vitro multidrug resistance in C. neoformans. Cells with the disrupted ISW1 gene exhibited profound resistance to multiple antifungal drugs. Mass spectrometry analysis revealed that Isw1 is both acetylated and ubiquitinated, suggesting that an interplay between these two modification events exists to govern Isw1 function. Mutagenesis studies of acetylation and ubiquitination sites …

Allergic Bronchopulmonary Aspergillosis: Radiological And Microbiological Profile Of Patients Presented In An Outpatient Pulmonary Clinic In A Developing Country, Nousheen Iqbal, Muhammad Irfan, Mustafa Bin Ali Zubairi, Maaha Ayub, Safia Awan, Kauser Jabeen, Ali Bin Sarwar Zubairi

Section of Pulmonary & Critical Care

There is limited data available about allergic bronchopulmonary aspergillosis (ABPA) in Pakistan. The aim of the study was to describe the radiological and microbiological profile of ABPA patients presenting to the outpatient pulmonary clinic of a tertiary care hospital in Karachi, Pakistan. A retrospective study was conducted on ABPA patients who presented to the pulmonary outpatient clinic at Aga Khan University Hospital, Karachi, Pakistan, from January 2017 to December 2019. Data was collected on microbiology and radiology features on predesigned proforma. A total of 7759 asthmatic patients presented at the outpatient pulmonology clinic during the study period. Of the 245 …

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 …

Correlation Of Acetylcholinesterase Activity And Bone Biochemical Markers In Premature And Full-Term Neonates, Khaled Mohammed Elsayed, Abd Elaziz Abd Elrahman Alnokaly, Mohammed Abd El-Malik Hassan, Mabrouk Mahmoud Abo Elenin

Al-Azhar International Medical Journal

Background: Prematurity lowers body weight and bone mineral density in nearly 30% of preterm newborns. Premature newborns are not screened for metabolic bone disease, hence bone biochemical markers should be investigated. Acetylcholinesterase mediates bone remodeling in recent investigations. Bone biochemical indicators and acetylcholinesterase (AChE) levels in preterm newborns may be linked. Objective: The aim of our study is to evaluate the probable correlation of AChE levels with multiple bone biomarkers in full-term and premature neonates. Subjects and Methods: This study was designed as a case control study. We examined 80 newborns (40 preterm with gestational age less than 37 weeks, …

Uterine Artery Doppler Indices As Determinant Of Success In Intra Cytoplasmic Sperm Injection, Abd-Elqawy Hendawy Shams, Fahd Abd Elall El Omda, Noha Mohamed Sabry

Al-Azhar International Medical Journal

Background: In-Vitro Fertilization (IVF). Patients with infertility are usually advised to have intracytoplasmic sperm injections (ICSI). Doppler ultrasound, which uses high frequency transvaginal probes and coloured pictures, is one of the most frequently used methods in this field. One of the parameters supplied by an ultrasonographic test for determining the success of IVF includes endometrial thickness, endometrial pattern, endometrial volume, and endometrial blood flow. Aim: To detect implantation window using uterine artery indices in ICSI cycles. Subject and Methods: This study will be concluded at the assisted reproductive techniques unit of AlAzhar University on 100 patients. Results: Regarding BMI, there …

Reporting Of Mycetoma Cases From Skin And Soft Tissue Biopsies Over A Period Of Ten Years: A Single Center Report And Literature Review From Pakistan, Mohammad Zeeshan, Saira Fatima, Joveria Farooqi, Kauser Jabeen, Arsalan Ahmed, Afreen Haq, Muhammad Omer Arif, Afia Zafar

Department of Pathology and Laboratory Medicine

Background: Mycetoma is an important neglected tropical disease associated with debilitation, disfigurement and death if not diagnosed and treated adequately. In Pakistan, mycetoma cases have frequently been diagnosed in histopathology and microbiology laboratories. However, there is scarcity of published data from this country. Therefore, the objectives of this study were to evaluate the frequency and type of mycetoma reported in skin and soft tissue biopsies from a single center over 10 years and review of published literature from Pakistan.
Method: This descriptive observational retrospective study was conducted at the Aga Khan University Hospital laboratory, Karachi, Pakistan. Laboratory data from 2009-2018 …

Evaluation Of Stratified Antibiograms For Use In Laboratory And Antimicrobial Stewardship, Linsey Donner

Theses & Dissertations

Antibiograms are critical for choosing empiric antimicrobial therapy. Cumulative antibiograms, which aggregate susceptibility data, can mask differences within specific patient subsets or clinical syndromes. This dissertation was done to determine if antibiotic susceptibilities showed substantial differences when comparing stratified antibiograms to cumulative antibiograms.

Antibiotic susceptibility data was retrospectively obtained from Nebraska Medicine January 1, 2017 – December 31, 2019 for Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis. The University of Nebraska Medical Center’s web antibiogram clinical decision support tool was used to export the data. Bacteria-antibiotic susceptibility rates of stratified antibiograms …

Comparison Of Antimicrobial Efficacy Of Calcipex And Metapex In Endodontic Treatment Of Chronic Apical Periodontitis: A Randomised Controlled Trial Study Protocol, Momina Motiwala, Saqib Habib, Rabia Ghafoor, Seema Irfan

Section of Dental-Oral Maxillofacial Surgery

Introduction: Various intracanal medicaments have been used in cases of chronic apical periodontitis for appropriate disinfection of the root canal system to eliminate microbes especially from the inaccessible areas. Calcium hydroxide is the most common intracanal medicament available in various forms, but its effectiveness with or without iodoform using microbial culture is unknown. Therefore, our aim is to compare the antimicrobial efficacy of Calcipex and Metapex in endodontic treatment of teeth presenting with chronic apical periodontitis by assessing the bacterial load reduction.
Method and analysis: 60 single rooted teeth of patients with diagnosis of chronic apical periodontitis will be selected …

The Role Of Interspecies Recombination In The Evolution Of Antibiotic-Resistant Pneumococci, Joshua C. D'Aeth, Mark Pg Van Der Linden, Lesley Mcgee, Herminia De Lencastre, Paul Turner, Jae-Hoon Song, Stephanie W. Lo, Rebecca A. Gladstone, Gps Consortium, Sadia Shakoor

Department of Pathology and Laboratory Medicine

Multidrug-resistant Streptococcus pneumoniae emerge through the modification of core genome loci by interspecies homologous recombinations, and acquisition of gene cassettes. Both occurred in the otherwise contrasting histories of the antibiotic-resistant S. pneumoniae lineages PMEN3 and PMEN9. A single PMEN3 clade spread globally, evading vaccine-induced immunity through frequent serotype switching, whereas locally circulating PMEN9 clades independently gained resistance. Both lineages repeatedly integrated Tn916-type and Tn1207.1-type elements, conferring tetracycline and macrolide resistance, respectively, through homologous recombination importing sequences originating in other species. A species-wide dataset found over 100 instances of such interspecific acquisitions of resistance cassettes and flanking …

Case Of Enterococcus Cecorum Human Bacteremia, United States, Alexander D. Lake, Ryan Fields, Francia Guerrero, Yousef Almuzaini, Koravangala Sundaresh, Joseph Staffetti

HCA Healthcare Journal of Medicine

Enterococcus cecorum rarely serves as a human pathogen, and only 6 cases of this microbe inoculating humans have been documented. We present an elderly female with a marked vascular history presenting with epigastric pain and diarrhea, followed by shaking chills. Laboratory findings revealed leukocytosis, with imaging showing diffuse colonic thickening. She had a bout of bloody diarrhea, raising the likelihood of ischemic colitis with her vascular history. To our surprise, both sets of blood cultures drawn on admission grew Enterococcus cecorum. This case is unique as it is the first documented case of E. cecorum human infection in the …

Etiology, Clinical, Radiological, And Microbiological Profile Of Patients With Non-Cystic Fibrosis Bronchiectasis At A Tertiary Care Hospital Of Pakistan, Nadia Sharif, Mirza Saifullah Baig, Sana Sharif, Muhammad Irfan

Section of Pulmonary & Critical Care

Objectives: To identify the etiology of non-cystic fibrosis bronchiectasis (NCFB), to assess the clinical presentation, radiological findings, and microbiological profile of patients presenting with a diagnosis of bronchiectasis in a tertiary care center of Pakistan.
Methods: This was a prospective observational cohort study where patients with a diagnosis of bronchiectasis proven by high-resolution computed tomography (HRCT) were evaluated for etiology, clinical characteristics, microbiology, radiology, spirometric profile, and in-hospital outcomes.
Results: During the study period, 196 patients were diagnosed with NCFB. The majority of the patients were men 76.5% (n = 150) and 83.6% (n = 163) of the total patients …

Practical Guidance For Clinical Microbiology Laboratories: Viruses Causing Acute Respiratory Tract Infections, C. L. Charlton, E. Babady, C. C. Ginocchio, T. F. Hatchette, R. C. Jerris, Y. Li, M. Loeffelholz, Y. S. Mccarter, M. B. Miller, S. J. Drews, +4 Additional Authors

Journal Articles

No abstract provided.

Quantitative Human Immunodeficiency Virus (Hiv)-1 Antibodies Correlate With Plasma Hiv-1 Rna And Cell-Associated Dna Levels In Children On Antiretroviral Therapy, M. Mcmanus, J. Henderson, A. Gautam, R. Brody, E. R. Weiss, D. Persaud, E. Mick, K. Luzuriaga, V. Bonagura, I. Febo, +22 Additional Authors

Journal Articles

No abstract provided.

Examination Of Fluconazole-Induced Alopecia In An Animal Model And Human Cohort, G. R. Thompson, C. R. Krois, V. K. Affolter, A. D. Everett, E. K. Varjonen, V. R. Sharon, A. Singapuri, M. Dennis, I. Mchardy, S. D. White, +6 Additional Authors

Journal Articles

No abstract provided.

Intestinal Microbiota And Weight-Gain In Preterm Neonates, Silvia Arboleya, Pablo Martinez-Camblor, Gonzalo Solís, Marta Suárez

Dartmouth Scholarship

The involvement of the gut microbiota on weight-gain and its relationship with childhood undernutrition and growth has been reported. Thus, the gut microbiota constitutes a potential therapeutic target for preventing growth impairment. However, our knowledge in this area is limited. In this study we aimed at evaluating the relationship among early microbiota, growth, and development in preterm infants. To this end we assessed the levels of specific microorganisms by qPCR, and those of short chain fatty acids by mean of gas-chromatography, in feces from 63 preterm newborns and determined their weight-gain during the first months. The statistical analyses performed indicate …

Diagnostic Methods To Determine Microbiology Of Postpartum Endometritis In South Asia: Laboratory Methods Protocol Used In The Postpartum Sepsis Study: A Prospective Cohort Study, Sadia Shakoor, Megan E. Reller, Amnesty Lefevre, Aneeta Hotwani, Shahida M. Qureshi, Farheen Yousuf, Mohammad Shahidul Islam, Nicholas Connor, Iftekhar Rafiqullah, Fatima Mir

Department of Paediatrics and Child Health

Background: The South Asian region has the second highest risk of maternal death in the world. To prevent maternal deaths due to sepsis and to decrease the maternal mortality ratio as per the World Health Organization Millenium Development Goals, a better understanding of the etiology of endometritis and related sepsis is required. We describe microbiological laboratory methods used in the maternal Postpartum Sepsis Study, which was conducted in Bangladesh and Pakistan, two populous countries in South Asia.
Methods/Design: Postpartum maternal fever in the community was evaluated by a physician and blood and urine were collected for routine analysis and culture. …

A Multiscale Mapping Assessment Of Lake Champlain Cyanobacterial Harmful Algal Blooms, Nathan Torbick, Megan Corbiere, Yu-Pin Lin

Dartmouth Scholarship

Lake Champlain has bays undergoing chronic cyanobacterial harmful algal blooms that pose a public health threat. Monitoring and assessment tools need to be developed to support risk decision making and to gain a thorough understanding of bloom scales and intensities. In this research application, Landsat 8 Operational Land Imager (OLI), Rapid Eye, and Proba Compact High Resolution Imaging Spectrometer (CHRIS) images were obtained while a corresponding field campaign collected in situ measurements of water quality. Models including empirical band ratio regressions were applied to map chlorophylla and phycocyanin concentrations; all sensors performed well with R² and root-mean-square error (RMSE) ranging …

A Self-Lysis Pathway That Enhances The Virulence Of A Pathogenic Bacterium, Kirsty A. Mcfarland, Emily L. Dolben, Michele Leroux, Tracy K. Kambara, Kathryn Ramsey, Robin Kirkpatrick, Joseph Mougous, Deborah Hogan, Simon Dove

Dartmouth Scholarship

In mammalian cells, programmed cell death (PCD) plays important roles in development, in the removal of damaged cells, and in fighting bacterial infections. Although widespread among multicellular organisms, there are relatively few documented instances of PCD in bacteria. Here we describe a potential PCD pathway in Pseudomonas aeruginosa that enhances the ability of the bacterium to cause disease in a lung infection model. Activation of the system can occur in a subset of cells in response to DNA damage through cleavage of an essential transcription regulator we call AlpR. Cleavage of AlpR triggers a cell lysis program through de-repression of …

Draft Genome Sequences Of Six Different Staphylococcus Epidermidis Clones, Isolated Individually From Preterm Neonates Presenting With Sepsis At Edinburgh's Royal Infirmary, Paul Walsh, M. Bekaert, J. Carroll, T. Manning, B. Kelly, A. O'Driscoll, X. Lu, C. Smith, P. Dickinson, K. Templeton, P. Ghazal, Roy D. Sleator

Department of Biological Sciences Publications

Herein, we report the draft genome sequences of six individual Staphylococcus epidermidis clones, cultivated from blood taken from different preterm neonatal sepsis patients at the Royal Infirmary, Edinburgh, Scotland, United Kingdom.

Site-Specific Mutation Of The Sensor Kinase Gras In Staphylococcus Aureus Alters The Adaptive Response To Distinct Cationic Antimicrobial Peptides, Ambrose L. Cheung, Arnold S. Bayer, Michael R. Yeaman, Yan Q. Xiong, Alan J. Waring, Guido Memmi, Niles Donegan

Dartmouth Scholarship

The Staphylococcus aureus two-component regulatory system, GraRS, is involved in resistance to killing by distinct host defense cationic antimicrobial peptides (HD-CAPs). It is believed to regulate downstream target genes such as mprF and dltABCD to modify the S. aureus surface charge. However, the detailed mechanism(s) by which the histidine kinase, GraS, senses specific HD-CAPs is not well defined. Here, we studied a well-characterized clinical methicillin-resistant S. aureus (MRSA) strain (MW2), its isogenic graS deletion mutant (ΔgraS strain), a nonameric extracellular loop mutant (ΔEL strain), and four residue-specific ΔEL mutants (D37A, P39A, P39S, and D35G D37G D41G strains). The ΔgraS and …

Acidosis Potentiates The Host Proinflammatory Interleukin-1Β Response To Pseudomonas Aeruginosa Infection, I. M. Torres, Y. R. Patankar, Tamer B. Shabaneh, E. Dolben, Deborah Hogan, David Leib, Brent L. Berwin

Dartmouth Scholarship

Infection by Pseudomonas aeruginosa, and bacteria in general, frequently promotes acidification of the local microenvironment, and this is reinforced by pulmonary exertion and exacerbation. However, the consequence of an acidic environment on the host inflammatory response to P. aeruginosa infection is poorly understood. Here we report that the pivotal cellular and host proinflammatory interleukin-1β (IL-1β) response, which enables host clearance of the infection but can produce collateral inflammatory damage, is increased in response to P. aeruginosa infection within an acidic environment. Synergistic mechanisms that promote increased IL-1β release in response to P. aeruginosa infection in an acidic environment are …

Human And Helicobacter Pylori Coevolution Shapes The Risk Of Gastric Disease, Nuri Kodaman, Alvaro Pazos, Barbara G. Schneider, M. Blanca Piazuelo, Robertino Mera, Rafal S. Sobota

Dartmouth Scholarship

Helicobacter pylori is the principal cause of gastric cancer, the second leading cause of cancer mortality worldwide. However, H. pylori prevalence generally does not predict cancer incidence. To determine whether coevolution between host and pathogen influences disease risk, we examined the association between the severity of gastric lesions and patterns of genomic variation in matched human and H. pylori samples. Patients were recruited from two geographically distinct Colombian populations with significantly different incidences of gastric cancer, but virtually identical prevalence of H. pylori infection. All H. pylori isolates contained the genetic signatures of multiple ancestries, with an ancestral African cluster …

Epoxide-Mediated Cifr Repression Of Cif Gene Expression Utilizes Two Binding Sites In Pseudomonas Aeruginosa, Alicia E. Ballok, Christopher D. Bahl, Emily L. Dolben, Allia K. Lindsay, Jessica D. St. Laurent, Deborah Hogan, Dean Madden, George A. O'Toole

Dartmouth Scholarship

Pseudomonas aeruginosa secretes an epoxide hydrolase virulence factor that reduces the apical membrane expression of ABC transporters such as the cystic fibrosis transmembrane conductance regulator (CFTR). This virulence factor, named CFTR inhibitory factor (Cif), is regulated by a TetR-family, epoxide-responsive repressor known as CifR via direct binding and repression. We identified two sites of CifR binding in the intergenic space between cifR and morB, the first gene in the operon containing the cif gene. We have mapped these binding sites and found they are 27 bp in length, and they overlap the -10 and +1 sites of both the cifR …

Two Boundaries Separate Borrelia Burgdorferi Populations In North America, Gabriele Margos, Jean I. Tsao, Santiago Castillo-Ramirez, Yvette A. Girard, Anne G. Hoen

Dartmouth Scholarship

Understanding the spread of infectious diseases is crucial for implementing effective control measures. For this, it is important to obtain information on the contemporary population structure of a disease agent and to infer the evolutionary processes that may have shaped it. Here, we investigate on a continental scale the population structure of Borrelia burgdorferi, the causative agent of Lyme borreliosis (LB), a tick-borne disease, in North America. We test the hypothesis that the observed d population structure is congruent with recent population expansions and that these were preceded by bottlenecks mostly likely caused by the near extirpation in the 1900s …

Eat, Drink And Be Wary, Robert Lannigan

Pathology Presentations

The diversity of foods available and the way we produce, process and distribute them can have consequences in terms of infectious illnesses. This talk by Dr. Robert Lannigan, professor in Western’s Schulich School of Medicine & Dentistry, explores some of these concerns.

Long-Term Immunity To Lethal Acute Or Chronic Type Ii Toxoplasma Gondii Infection Is Effectively Induced In Genetically Susceptible C57bl/6 Mice By Immunization With An Attenuated Type I Vaccine Strain, Jason P. Gigley, Barbara A. Fox, David J. Bzik

Dartmouth Scholarship

C57BL/6 (B6) mice are genetically highly susceptible to chronic type II Toxoplasma gondii infections that invariably cause lethal toxoplasmic encephalitis. We examined the ability of an attenuated type I vaccine strain to elicit long-term immunity to lethal acute or chronic type II infections in susceptible B6 mice. Mice immunized with the type I cps1-1 vaccine strain were not susceptible to a lethal (100-cyst) challenge with the type II strain ME49. Immunized mice challenged with 10 ME49 cysts exhibited significant reductions in brain cyst and parasite burdens compared to naive mice, regardless of the route of challenge infection. Remarkably, cps1-1 strain-immunized …

Uncoupling Scavenger Receptor A-Mediated Phagocytosis Of Bacteria From Endotoxic Shock Resistance, Eyal Amiel, Julie L. Acker, Ryan M. Collins, Brent Berwin

Dartmouth Scholarship

Unresolved infection by gram-negative bacteria can result in the potentially lethal condition known as endotoxic shock, whereby uncontrolled inflammation can lead to multiple organ failure and death of the infected host. Previous results have demonstrated that animals deficient in class A scavenger receptor (SRA), a trafficking receptor for bacteria and bacterium-derived molecules, are more susceptible to endotoxic shock. This has been proposed to be a result of impaired SRA-dependent phagocytic clearance of bacteria resulting in stronger proinflammatory stimuli. In this report, we test the hypothesis that there is an obligate reciprocal relationship between SRA-mediated phagocytosis of bacteria and susceptibility to …

Flagellum-Mediated Biofilm Defense Mechanisms Of Pseudomonas Aeruginosa Against Host-Derived Lactoferrin, Jeff G. Leid, Mathias Kerr, Candice Selgado, Chelsa Johnson, Gabriel Moreno, Alyssa Smith, Mark E. Shirtliff, Georg A. O'Toole, Emily K. Cope

Dartmouth Scholarship

Chronic infection with the gram-negative organism Pseudomonas aeruginosa is a leading cause of morbidity and mortality in human patients, despite high doses of antibiotics used to treat the various diseases this organism causes. These infections are chronic because P. aeruginosa readily forms biofilms, which are inherently resistant to antibiotics as well as the host's immune system. Our laboratory has been investigating specific mutations in P. aeruginosa that regulate biofilm bacterial susceptibility to the host. To continue our investigation of the role of genetics in bacterial biofilm host resistance, we examined P. aeruginosa biofilms that lack the flgK gene. This mutant …

Long-Distance Delivery Of Bacterial Virulence Factors By Pseudomonas Aeruginosa Outer Membrane Vesicles, Jennifer M. Bomberger, Daniel P. Maceachran, Bonita A. Coutermarsh, Siying Ye, George A. O'Toole, Bruce A. Stanton, Frederick M. Ausubel

Dartmouth Scholarship

Bacteria use a variety of secreted virulence factors to manipulate host cells, thereby causing significant morbidity and mortality. We report a mechanism for the long-distance delivery of multiple bacterial virulence factors, simultaneously and directly into the host cell cytoplasm, thus obviating the need for direct interaction of the pathogen with the host cell to cause cytotoxicity. We show that outer membrane–derived vesicles (OMV) secreted by the opportunistic human pathogen Pseudomonas aeruginosa deliver multiple virulence factors, including β-lactamase, alkaline phosphatase, hemolytic phospholipase C, and Cif, directly into the host cytoplasm via fusion of OMV with lipid rafts in the host plasma …