Medicine and Health Sciences Commons^™

Illuminating The Dark Side-Vitamin D Status In Different Localities Of Karachi, Romaina Iqbal, Lena Jafri, Ali Haroon, Aysha Habib Khan

Department of Pathology and Laboratory Medicine

This study was conducted to determine the association between place of residence (grouped into neighbourhoods), and 25-hydroxy D (25[OH]D) levels of individuals of Karachi. Addresses of 4788 individuals tested for 25[OH]D at the clinical laboratory of the Aga Khan University (AKU), Karachi, from January 2007 to June 2008 were reviewed. The neighbourhoods were categorized into ten, based on locality attributes. A high overall prevalence (74%) of vitamin D deficiency (VDD) was observed. There was a significant difference (p-value < 0.01) between mean log 25[OH]D levels amongst neighbourhoods grouped according to distinct housing structure attributes and localities. A high frequency of VDD in all the studied localities of an urban city warrant dietary vitamin D supplementation and food fortification.

Bioengineering The Expression Of Active Recombinant Human Cathepsin G, Enteropeptidase, Neutrophil Elastase, And C-Reactive Protein In Yeast, Eliot T. Smith

Electronic Theses and Dissertations

The yeasts Pichia pastoris and Kluyveromyces lactis were used to express several recombinant human proteins for further biochemical characterization. Two substitution variants of recombinant human enteropeptidase light chain (rhEPL) were engineered to modify the extended substrate specificity of this serine protease. Both were secreted as active enzymes in excess of 1.7 mg/L in P. pastoris fermentation broth. The substitution variant rhEPL R96Q showed significantly reduced specificities for the preferred substrate sequences DDDDK and DDDDR; however, the rhEPL Y174R variant displayed improved specificities for these substrate sequences relative to all other reported variants of this enzyme. The neutrophil serine proteases human …

Regulating Rsma Expression In Pseudomonas Aeruginosa, Sean D. Stacey

Electronic Theses and Dissertations

Pseudomonas aeruginosa, a Gram-negative bacillus, commonly infects immunocompromised individuals and uses a variety of virulence factors to persist in these hosts. The posttranscriptional regulator, RsmA, plays a role in the expression of many virulence factors in P. aeruginosa. RsmA up regulates virulence factors used in colonizing hosts. However, regulation of rsmA is not well elucidated. Transposon mutagenesis was performed on P. aeruginosa containing a transcriptional rsmA-lacZ fusion to answer this question. Mutants were screened via β-galactosidase assay and transposon insertions identified via arbitrary PCR. A probable MFS transporter, we named mtpX, was one significant transposon mutant identified. …

Evaluating The Utility Of Clinical Criteria For The Identification Of Lynch Syndrome Among Endometrial Cancer Patients, Amanda S. Bruegl

Dissertations and Theses (Open Access)

Background: Lynch Syndrome (LS) is a familial cancer syndrome with a high prevalence of colorectal and endometrial carcinomas among affected family members. Clinical criteria, developed from information obtained from familial colorectal cancer registries, have been generated to identify individuals at elevated risk for having LS. In 2007, the Society of Gynecologic Oncology (SGO) codified criteria to assist in identifying women presenting with gynecologic cancers at elevated risk for having LS. These criteria have not been validated in a population-based setting.

Materials and Methods: We retrospectively identified 412, unselected endometrial cancer cases. Clinical and pathologic information were obtained from the electronic …

T-Cell Treatments For Solid And Hematological Tumors, Drew C. Deniger

Dissertations and Theses (Open Access)

Cell-based therapies have demonstrated potency and efficacy as cancer treatment modalities. T cells can be dichotomized by their T cell receptor (TCR) complexes where alpha/beta T cells (95% of T cells) and gamma/delta T cells (+T cells proliferated to clinically significant numbers and ROR1⁺ tumor cells were effectively targeted and killed by both ROR1-specific CAR⁺ T cell populations, although ROR1RCD137 were superior to ROR1RCD28 in clearance of leukemia xenografts in vivo. The second specific aim focused on generating bi-specific CD19-specific CAR⁺ gamma/delta T cells with polyclonal TCRgamma/delta repertoire on CD19⁺ artificial antigen presenting cells (aAPC). …

Early Echocardiographic Changes After Percutaneous Implantation Of The Edwards Sapien Transcatheter Heart Valve In The Pulmonary Position., Shahryar M. Chowdhury, Ziyad M. Hijazi, John Rhodes, Saibal Kar, Raj Makkar, Michael Mullen, Qi-Ling Cao, Lydia King, Jodi Akin, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To evaluate echocardiographic changes after SAPIEN valve implantation in the pulmonary position.

BACKGROUND: The feasibility of the SAPIEN transcatheter pulmonary valve (TPV) has recently been demonstrated. We evaluated changes in pulmonary valve function and the right ventricle after SAPIEN TPV placement.

METHODS: We evaluated echocardiograms at baseline, discharge, 1 and 6 months after TPV placement in 33 patients from 4 centers. Pulmonary insufficiency severity was graded 0-4. TPV peak and mean gradients were measured. Right ventricular (RV) size and function were quantified using routine measures derived from color, spectral, and tissue Doppler indices and two-dimensional echocardiography.

RESULTS: At baseline, …

Macromolecular Complexes Of Cystic Fibrosis Transmembrane Conductance Regulator Alter Fluid Transport In Inflammatory Bowel Disorders, Kavisha Arora

Theses and Dissertations (ETD)

Macromolecular complexes of cystic fibrosis transmembrane conductance regulator (CFTR) comprise of network of proteins that can regulate cAMP-/cGMP-activated CFTR chloride channel function. We report the physical and functional coupling of CFTR with nitric oxide (NO) producing enzyme-inducible nitric oxide synthase (iNOS) at the apical plasma membrane in inflammatory bowel disease (IBD). The complex formation requires the scaffolding protein Na+ /H+ exchanger regulatory factor 2 (NHERF2). We demonstrate that iNOS is overexpressed at or near the apical plasma membrane of gut epithelial cells in IBD and, through the stimulation of the NO-cGMP pathway, generates compartmentalized cGMP underneath the plasma membrane. This …

An Insight Into The Microbial Diversity And Expression Of Cysteine Protease Inhibitors (Cystatin) In Rickettsia Parkeri Infected Amblyomma Maculatum, Khemraj Budachetri

Master's Theses

Amblyomma maculatum (Gulf Coast tick) is an emerging tick species of public health significance in United States. It is a competent vector of Rickettsia parkeri, an etiological agent of a human rickettsiosis. In this study, we investigated the spotted fever group of rickettsial diversity in A. maculatum based on rickettsial ompA gene PCR. Our results showed A. maculatum harbors R. parkeri, R. amblyommii, and R. endosymbiont of A. maculatum. While only R. parkeri was detected in female salivary glands which suggest its ability to traffic from midgut to salivary glands via hemocoel. The presence of R. parkeri was further …

Severe Combined Immune Deficiency Syndrome, Ali Faisal Saleem, Ranish Deedar Ali Khawaja, Abdul Sattar Shaikh, Syed Asad Ali, Anita Kaniz Mehdi Zaidi

Department of Paediatrics and Child Health

Objective: To determine the clinico-demographic features and laboratory parameters of children with severe combined immunodeficiency (SCID).

Study Design: Case series.

Place and Duration of Study: Department of Paediatrics and Child Health, the Aga Khan University, Karachi, from July 2006 to July 2011.

Methodology: Thirteen infants who were discharged with a diagnosis of SCID were inducted in the study. Their clinicodemographic features and laboratory parameters were determined. Descriptive statistics has been used for computing frequency and percentage.

Results: The median age at diagnosis was five months; 5 infants presented within 3 months of life. Three-fourth (77%) were males. Most of the …

Characterization Of Host Immune Responses To Eimeria Adenoeides Infection In Turkey Poults, Ujvala Deepthi Gadde

Graduate Theses and Dissertations

Coccidiosis is a common enteric disease of turkeys that is caused by protozoan parasites belonging to the genus Eimeria. There are about seven species of Eimeria that affect turkeys and of these E. adenoeides is the most pathogenic and commonly recognized. Infection with Eimeria is known to induce a long lasting protective immunity in chickens, but nothing is known regarding the acquisition of immunity to Eimeria in turkeys. The experiments reported here were aimed at investigating the biological and cellular immune response to E. adenoeides in turkey poults under different conditions of exposure. In experiment 1 (Chapter II), 20 …

System Design And Motion Artifact Removal Algorithm Implementation For Ambulatory Women Ecg Measurement System:E-Bra System, Hyeokjun Kwon

Graduate Theses and Dissertations

Cardio Vascular Disease (CVD) leads to sudden cardiac death due to irregular phenomenon of the cardiac signal by the abnormal case of blood vessel and cardiac structure. For last three decades, there is an enhanced interest in research for cardiac diseases.. As a result, the death rate by cardiac disease in men has been falling gradually compared with relatively increasing the death rate for women due to CVD. The main reason for this phenomenon is due to the lack of seriousness to female CVD and different symptoms of female CVD compared with the symptoms of male CVD. Usually, because the …

Comparison Of Potential Salmonella Portals Of Entry And Tissue Distribution Following Challenge Of Poultry, Gopala Krishna Kallapura Sheshagiri

Graduate Theses and Dissertations

The following studies evaluated our hypothesis that transmission by the fecal-respiratory route may be a viable portal of entry for Salmonella and could explain some clinical impressions of relatively low-dose infectivity under field conditions in relation to the requisite high oral challenge dose that is typically required for infection of poultry through the oral route in laboratory studies. Initial field reports indicating tracheal sampling to be a sensitive tool for monitoring Salmonella infection in commercial flocks, suggested that tracheal contamination could be a good indicator of Salmonella infection under commercial conditions. Further, a usual assumption regarding airborne Salmonella reaching the …

Ron Knockdown And Ron Monoclonal Antibody Imc-Ron8 Sensitize Pancreatic Cancer To Histone Deacetylase Inhibitors (Hdaci)., Yi Zou, Gillian M. Howell, Lisa E. Humphrey, J. Wang, Michael G. Brattain

Journal Articles: Eppley Institute

Recepteur d'origine nantais (Ron) is overexpressed in a panel of pancreatic cancer cells and tissue samples from pancreatic cancer patients. Ron can be activated by its ligand macrophage stimulating protein (MSP), thereby activating oncogenic signaling pathways. Crosstalk between Ron and EGFR, c-Met, or IGF-1R may provide a mechanism underlying drug resistance. Thus, targeting Ron may represent a novel therapeutic strategy. IMC-RON8 is the first Ron monoclonal antibody (mAb) entering clinical trial for targeting Ron overexpression. Our studies show IMC-RON8 downmodulated Ron expression in pancreatic cancer cells and significantly blocked MSP-stimulated Ron activation, downstream Akt and ERK phosphorylation, and survivin mRNA …

Going With The Flow Of Time, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Research Brief: "Weight Change Following U.S. Military Service", Institute For Veterans And Military Families At Syracuse University

Institute for Veterans and Military Families

This brief is about weight change among veterans before, during, and after discharge from the military. In policy and practice, physicians should discuss strategies to prevent unhealthy weight gain with veteran patients; the VA should better tailor its MOVE! weight management program to younger veterans. Suggestions for future research include looking at the reasons behind weight gain in discharged servicemembers, analyzing the strategies used by members of the Reserve/National Guard to limit weight gain, and using more samples of younger veterans to generalize results.

Humanitarianism And The Anthropology Of Hunger, Kate Klein

Undergraduate Theses—Unrestricted

While the early view of hunger as the product of a world population too large to sustain has largely been eliminated, and the mainstream international community has come to accept that food insecurity results from issues of distribution rather than an insufficient global food supply, the emphasis on biotechnology in agriculture, humanitarianism in international aid, and social justice in international human rights law in the contemporary era has contributed to other barriers that prevent hunger alleviation.

In this thesis, I argue that these previous contemporary developments have had the capacity to hide hunger. My analysis of technology and humanitarian aid …

The Association Between A Medical History Of Depression And Gestational Diabetes In A Large Multi-Ethnic Cohort In The United States, Katherine Bowers, S. Katherine Laughon, Sungduk Kim, Sunni L. Mumford, Jennifer Brite, Michele Kiely, Cuilin Zhang

Publications and Research

Background: Both major depression and gestational diabetes mellitus (GDM) are prevalent among women of reproductive age. Our objective was to determine whether a medical history of depression is related to subsequent development of GDM.

Methods: The Consortium on Safe Labor was a US retrospective cohort study of 228 562 births between 2002 and 2008. Exclusion criteria for the present analysis included multiple gestation pregnancies (n = 5059), pre-existing diabetes (n = 12 771), deliveries(n = 395), site GDM prevalence (

Results: The final analytic population included 121 260 women contributing 128 295 pregnancies, of which 5606 were affected by GDM. …

Spatially Explicit Modeling Of Schistosomiasis Risk In Eastern China Based On A Synthesis Of Epidemiological, Environmental, And Intermediate Host Genetic Data, Matthias Schrader, Torsten Hauffe, Zhijie Zhang, George M. Davis, Fred Jopp, Justin V. Remais, Thomas Wilke

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Schistosomiasis japonica is a major parasitic disease threatening millions of people in China. Though overall prevalence was greatly reduced during the second half of the past century, continued persistence in some areas and cases of re-emergence in others remain major concerns. As many regions in China are approaching disease elimination, obtaining quantitative data on Schistosoma japonicum parasites is increasingly difficult. This study examines the distribution of schistosomiasis in eastern China, taking advantage of the fact that the single intermediate host serves as a major transmission bottleneck. Epidemiological, population-genetic and high-resolution ecological data are combined to construct a predictive model capable …

Redefining Myocardial Infarction: What Is New In The Esc/Accf/Aha/Whf Third Universal Definition Of Myocardial Infarction?, Hani Jneid, Mahboob Alam, Salim S. Virani, Biykem Bozkurt

Office of the Provost

Myocardial infarction (MI) is a major cause of mortality and morbidity worldwide. Each year, an estimated 785,000 persons will have a new MI in the United States alone, and approximately every minute an American will succumb to one.1 In addition, MI has major psychological and legal implications for patients and the society and is an important outcome measure in research studies. The prevalence of MI provides useful data regarding the burden of coronary artery disease and offers insight into health care planning, policy, and resource allocation. The importance of accurately and reproducibly defining MI is therefore self-evident. The Third Universal …

Varied Presentation Of Celiac Disease In Pakistani Adults, Zaigham Abbas, Sajjad Raza, Javed Yakoob, Shahab Abid, Saeed Hamid, Hasnain Shah, Wasim Jafri

Section of Gastroenterology

he objective of this retrospective study was to evaluate presentation of celiac disease in adults. It included 77 patients, 41 (53.2%) males with median age 26 years and median body mass index of 18 (16 â�� 22) kg/m2. Typical presentation with gastrointestinal symptoms was seen in 76.6%. Atypical presentation with extra intestinal complaints in 7.8% and silent presentation in 15.6%. Major symptoms were diarrhea in 64.9%, weight loss 36.4%, abdominal pain 35.1%, vomiting 32.5%, pallor 24.7%, and weakness 13%. Iron deficiency was documented in 20.8%, B12 deficiency in 9.1%, folic acid deficiency in 6.5% and vitamin D deficiency in 10.4%. …

Changing Trends Of Hepatitis B Seromarkers Amongst Pakistani Population: A Laboratory-Based Review, Afia Zafar, Erum Khan, Muhammad Shoaib Khan, Bushra Moiz, Wasim Jafri

Section of Gastroenterology

Objective:

To study the changing trends of hepatitis B markers tested at Aga Khan University Hospital clinical laboratory according to the internationally recognised classification of hepatitis B profile.

Methods:

The retrospective study involved analysis of laboratory records of hepatitis B profiles of all patients collected from January 2001 to December 2008 at the Aga Khan University Hospital\'s clinical laboratory. Patients with complete profile tested were categorised according to the Centre for Diseases Control classification of hepatitis B profile. SPSS 16 was used for statistical analysis. R

Results:

A total of 185,825 patients had serological markers for hepatitis B tested. Mean-age …

Moderate Alcohol Use And Cardiovascular Disease From Mendelian Randomization, Shiu Lun Au Yeung, Chaoqiang Jiang, Kar Keung Cheng, Benjamin J. Cowling, Bin Liu, Weisen Zhang, Tai Hing Lam, Gabriel M. Leung, Mary Schooling

Publications and Research

Background
Observational studies show moderate alcohol use negatively associated with ischemic heart disease (IHD) and cardiovascular disease (CVD). However, healthier attributes among moderate users compared to never users may confound the apparent association. A potentially less biased way to examine the association is Mendelian randomization, using alcohol metabolizing genes which influence alcohol use.

Methods
We used instrumental variable analysis with aldehyde dehydrogenase 2 (ALDH2) genotypes (AA/GA/GG) as instrumental variables for alcohol use to examine the association of alcohol use (10 g ethanol/day) with CVD risk factors (blood pressure, lipids and glucose) and morbidity (self-reported IHD and CVD) among men in …

The Longitudinal Course Of Attention Deficit/Hyperactivity Disorder In Velo-Cardio-Facial Syndrome, Kevin M. Antshel, Kaitlin Hendricks, Robert J. Shprintzen, Wanda Fremont, Anne Marie Higgins, Stephen V. Faraone, Wendy R. Kates

Communication Disorders Faculty Publications

OBJECTIVE: To evaluate predictors of persistence of attention deficit/hyperactivity disorder (ADHD) in a large sample of children with velo-cardio-facial syndrome (VCFS) with and without ADHD followed prospectively into adolescence. STUDY DESIGN: Children with VCFS with (n = 37) and without (n = 35) ADHD who were on average 11 years old at the baseline assessment and 15 years old at the follow-up assessment were comprehensively assessed with structured diagnostic interviews and assessments of behavioral, cognitive, social, school, and family functioning. Control participants both with and without ADHD were also followed prospectively. RESULTS: In adolescence, 65% of children with VCFS continued …

Effectiveness Of Pentavalent And Monovalent Rotavirus Vaccines In Concurrent Use Among Us Children <5 Years Of Age, 2009-2011, Daniel C. Payne, Julie A. Boom, Mary Allen Staat, Kathryn M. Edwards, Peter G. Szilagyi, Eileen J. Klein, Rangaraj Selvarangan, Parvin H. Azimi, Christopher J. Harrison, Mary Moffatt, Samantha H. Johnston, Leila C. Sahni, Carol J, Baker, Marcia A. Rench, Stephanie Donauer, Monica Mcneal, James Chappell, Geoffrey A. Weinberg, Azadeh Tasslimi, Jacqueline E. Tate, Mary Wikswo, Aaron T. Curns, Iddrisu Sulemana, Slavica Mijatovic-Rustempasic, Mathew D. Esona, Michael D. Bowen, Jon R. Gentsch, Umesh D. Parashar

Manuscripts, Articles, Book Chapters and Other Papers

Background We assessed vaccine effectiveness (VE) for RotaTeq (RV5; 3 doses) and Rotarix (RV1; 2 doses) at reducing rotavirus acute gastroenteritis (AGE) inpatient and emergency department (ED) visits in US children.

Methods We enrolled children vaccine, age, ethnicity, genotype, and clinical setting.

Results RV5-specific analyses included 359 rotavirus cases and 1811 rotavirus-negative AGE controls. RV1-specific analyses included 60 rotavirus cases and 155 rotavirus-negative AGE controls. RV5 and RV1 were 84% (95% confidence interval [CI], 78%-88%) and 70% (95% CI, 39%-86%) effective, respectively, against rotavirus-associated ED visits and hospitalizations combined. By clinical setting, RV5 VE against ED and inpatient rotavirus-associated visits …

Effect Of A Lateral Wedge Insole Over A One Week Period In A Healthy Population, Sarah E. Sudheimer

Human Movement Studies & Special Education Theses & Dissertations

Medial knee osteoarthritis is a disease that is projected to affect approximately 45% of the U.S. population and is associated with significant morbidity, chronic pain, and limited activity. Laterally wedged insoles are used as an intervention to laterally shift the mechanical axis of the limb and decrease the external knee adduction moment, possibly indicating a shift in load distribution to the lateral compartment of the knee. The aim of this study was to examine the acute effects of a laterally wedged insole in those with valgus and normally aligned knees and to determine prolonged effects after the insole was worn …

In Vitro Selection Of Chloroquine Tolerant Plasmodium Falciparum Parasites, Daniel A. Daley

Biological Sciences Theses & Dissertations

Malaria is among the most devastating human diseases, and a majority of lethal cases are caused by the protozoan parasite, Plasmodiumfalciparum. The emergence of multi-drug resistant P.falciparum is a major obstacle to malaria control and is highlighted by the abandonment of chloroquine (CQ) as a first-line treatment of P.falciparum infections worldwide. Chloroquine resistance (CQR) is associated primarily with mutations in the transmembrane digestive vacuole protein, PfCRT. However, CQR P.falciparum parasites harboring the same mutant pfcrt allele vary in their CQ response, suggesting the CQ response is multigenic in nature. No gene outside of pfcrt is completely associated with CQR. Thus, …

The Protumorigenic Role Of Caspase-8 In Neuroblastoma, Devin Drew Twitchell

Theses and Dissertations (ETD)

Neuroblastoma (NB), the most common extracranial solid tumor in children, accounts for 15% of cancer-related deaths in pediatric patients. Caspase-8 (casp8), a proapoptotic protein, is silenced in approximately, 50-70% of neuroblastoma patient samples. Loss of casp8 has been suggested to increase NB metastasis and correlated, in some studies, with advanced-stage NB. Furthermore, decreased casp8 expression may facilitate neuroblastoma tumorigenesis by protecting cells from cell death mediated by either integrins or chemotherapeutics. Paradoxically, casp8 expression is maintained in 30-50% of NB patient samples giving rise to the possibility that casp8 may provide selective advantages for NB tumorigenesis. Caspase-8 is shown to …

Id4 Deficiency Attenuates Prostate Development And Promotes Pin-Like Lesions By Regulating Androgen Receptor Activity And Expression Of Nkx3.1 And Pten, Pankaj Sharma, Ashley Knowell, Swathi Chinaranagari, Shravan Komaragiri, Peri Nagappan, Divya Patel, Mathew C. Havrda, Jaideep Chaudhary

Dartmouth Scholarship

Background: Inhibitor of differentiation 4 (Id4), a member of the helix-loop-helix family of transcriptional regulators has emerged as a tumor suppressor in prostate cancer. Id4 is expressed in the normal prostate where its expression is also regulated by androgens. In this study we investigated the effect of loss of Id4 (Id4-/-) on adult prostate morphology. Methods: Histological analysis was performed on prostates from 6-8 weeks old Id4-/-, Id4+/- and Id4+/+ mice. Expression of Id1, Sox9, Myc, androgen receptor, Akt, p-Akt, Pten and Nkx3.1 was investigated by immunohistochemistry. Androgen receptor binding on NKX3.1 promoter was studied by chromatin immuno-precipitation. Id4 was …

A Simple And Computationally Efficient Approach To Multifactor Dimensionality Reduction Analysis Of Gene-Gene Interactions For Quantitative Traits, Jiang Gui, Jason H. Moore, Scott M. Williams, Peter Andrews, Hillege, Hans L. Hillege, Hans L., Pim Van Der Harst, Gerjan| Navis, Wiek H. Van Gilst, Folkert W. Asselbergs, Diane| Gilbert-Diamond

Dartmouth Scholarship

We present an extension of the two-class multifactor dimensionality reduction (MDR) algorithm that enables detection and characterization of epistatic SNP-SNP interactions in the context of a quantitative trait. The proposed Quantitative MDR (QMDR) method handles continuous data by modifying MDR’s constructive induction algorithm to use a T-test. QMDR replaces the balanced accuracy metric with a T-test statistic as the score to determine the best interaction model. We used a simulation to identify the empirical distribution of QMDR’s testing score. We then applied QMDR to genetic data from the ongoing prospective Prevention of Renal and Vascular End-Stage Disease (PREVEND) study.

The Obesity Epidemic, Lenka Kollar, Evienne Epifano, Molly Mckneight, Jeff Miskovich, Heather Moore

Student Papers in Public Policy

The incidence of chronic, noncommunicable diseases, such as heart disease, is increasing at an alarming rate on the global scale. The growing prevalence of overweight and obesity have led to an upsurge in cases of diabetes and other obesity-related diseases. About 18 million people die every year from heart disease, of which diabetes and obesity are major predisposing factors. Worldwide, more than 1.1 billion adults are overweight, 312 million of which are obese. The number of children that are overweight or obese is also growing (Hossain, Parvez et al.). Obesity, and the associated diseases, has become a worldwide epidemic and …