Digital Commons Network^™

Use Of Coronary Techniques In Celiac And Hepatic Artery Stenting In Post-Hepatic Transplant Patients, Harpreet Parmar, Ryan Beard, Mark W. Mewissen, Armaan Shaikh, Tanvir Bajwa

Journal of Patient-Centered Research and Reviews

Hepatic artery stenosis (HAS) remains a rare but serious complication after liver transplantation. While invasive surgical techniques were needed for HAS treatment in the past, recently endovascular techniques, including hepatic artery stenting, have been proven to be a safe and effective treatment. The present work focused on a review of the recent literature regarding HAS as well as recent cases demonstrating the various presentations of HAS and the variety of approaches to endovascular intervention. Our single-center experience has shown endovascular treatment of HAS to be safe and effective, including the two specific cases discussed here. While further research is needed, …

Novel Oral Anticoagulants For Stroke Prophylaxis And Venous Thromboembolism Prevention And Treatment, Laith G. Alsayegh

Journal of Patient-Centered Research and Reviews

Novel oral anticoagulants (NOACs) are becoming popular management options for stroke prophylaxis in nonvalvular atrial fibrillation as well as deep vein thrombosis and pulmonary embolism treatment and prophylaxis. NOACs have similar efficacy to warfarin along with noninferior safety profiles. Patient comorbidities, size, renal and hepatic function, and concomitant drug regimen play a role in which NOAC a physician may choose.

Fruit And Vegetable Consumption And Cardiovascular Risk Factors In Older Chinese: The Guangzhou Biobank Cohort Study, Yangbo Sun, Chao Qiang Jiang, Kar Keung Cheng, Wei Sen Zhang, Gabriel M. Leung, Tai Hing Lam, Mary Schooling

Publications and Research

Objective
To examine the adjusted associations of fruit consumption and vegetable consumption with the Framingham score and its components in the non-Western setting of Southern China, considering health status.

Method
Linear regression was used to assess the cross-sectional associations of fruit and vegetable consumption with the Framingham score and its components, among 19,518 older Chinese (50 years) from the Guangzhou Biobank Cohort Study in Southern China (2003– 2006), and whether these differed by health status.

Results
The association of fruit consumption with the Framingham score varied by health status (P-value

Conclusion
This large study from a non-western setting found that …

Investigation Of Stilbenoids As Potential Therapeutic Agents For Rotavirus Gastroenteritis, Judith M. Ball, Fabricio Medina-Bolivar, Katelyn D. Defrates, Emily Hambleton, Megan E. Hurlburt, Lingling Fang, Tianhong Yang, Luis Nopo-Olazabal, Richard L. Atwill, Pooj Ghai, Rebecca D. Parr

Faculty Publications

Rotavirus (RV) infections cause severe diarrhea in infants and young children worldwide. Vaccines are available but cost prohibitive for many countries and only reduce severe symptoms. Vaccinated infants continue to shed infectious particles, and studies show decreased efficacy of the RV vaccines in tropical and subtropical countries where they are needed most. Continuing surveillance for new RV strains, assessment of vaccine efficacy, and development of cost effective antiviral drugs remain an important aspect of RV studies. This study was to determine the efficacy of antioxidant and anti-inflammatory stilbenoids to inhibit RV replication. Peanut (A. hypogaea) hairy root cultures were induced …

Muc16-Mediated Activation Of Mtor And C-Myc Reprograms Pancreatic Cancer Metabolism., Surendra K. Shukla, Venugopal Gunda, Jaime Abrego, Dhanya Haridas, Anusha Mishra, Joshua J. Souchek, Nina V. Chaika, Fang Yu, Aaron R. Sasson, A Lazenby, Surinder K. Batra, Pankaj K. Singh

Journal Articles: Eppley Institute

MUC16, a transmembrane mucin, facilitates pancreatic adenocarcinoma progression and metastasis. In the current studies, we observed that MUC16 knockdown pancreatic cancer cells exhibit reduced glucose uptake and lactate secretion along with reduced migration and invasion potential, which can be restored by supplementing the culture media with lactate, an end product of aerobic glycolysis. MUC16 knockdown leads to inhibition of mTOR activity and reduced expression of its downstream target c-MYC, a key player in cellular growth, proliferation and metabolism. Ectopic expression of c-MYC in MUC16 knockdown pancreatic cancer cells restores the altered cellular physiology. Our LC-MS/MS based metabolomics studies indicate global …

Changes In Vessel Properties During Early Progression Of Murine Abdominal Aortic Aneurysms From In Vivo Ultrasound, Luis R. Avila Murati, Evan H. Phillips, Craig J. Goergen

The Summer Undergraduate Research Fellowship (SURF) Symposium

Abdominal aortic aneurysms (AAA) are a common and frequently fatal disease characterized by the weakening and dilation of the aorta. The larger the aneurysm, the higher the chances are of rupturing and life-threatening hemorrhage. The aim of this study is to apply the angiotensin II (AngII) model of AAAs in male apolipoprotein-E-deficient mice (apoE^-/- C57Bl/6J), in order to analyze, quantify, and understand the pathologies and characteristics associated with early AAA development. To date, many studies focusing on the evaluation of AAA characteristics have been performed ex vivo. Therefore, we focused on in vivo assessment, through the use of …

Microrna-587 Antagonizes 5-Fu-Induced Apoptosis And Confers Drug Resistance By Regulating Ppp2r1b Expression In Colorectal Cancer., Yinbo Zhang, Geoffrey Talmon, Jing Wang

Journal Articles: Eppley Institute

Drug resistance is one of the major hurdles for cancer treatment. However, the underlying mechanisms are still largely unknown and therapeutic options remain limited. In this study, we show that microRNA (miR)-587 confers resistance to 5-fluorouracil (5-FU)-induced apoptosis in vitro and reduces the potency of 5-FU in the inhibition of tumor growth in a mouse xenograft model in vivo. Further studies indicate that miR-587 modulates drug resistance through downregulation of expression of PPP2R1B, a regulatory subunit of the PP2A complex, which negatively regulates AKT activation. Knockdown of PPP2R1B expression increases AKT phosphorylation, which leads to elevated XIAP expression and enhanced …

End Stage Renal Disease: Seroprevalence Of Hepatitises B And C Along With Associated Aetiology And Risk Factors In Children, Syed Raza Shah, Muhammad Shahzeb Khan, Muhamad Tanveer Alam, Adnan Salim, Mehwish Hussain, Areeba Altaf

Section of Neurosurgery

Background: End Stage Renal Disease (ESRD) normally requires dialysis or transplantation for survival. Since ESRD patients are on long term dialysis, infections such as Hepatitis B (HBV) and Hepatitis C (HCV) are commonly reported.
Methods: This was a retrospective study carried out at a government hospital during a 12-month period from January 2013 to December 2013. The data was collected using a predesigned pro forma to note the etiology, gender, age, and HBsAg and anti-HCV test result of each patient.
Results: 444 children suffering from ESRD were included in our analysis. The mean age of sample was 12.7 ± 4.1 …

The Right Tool For The Job: Detection Of Soil-Transmitted Helminths In Areas Co-Endemic For Other Helminths, Maria V. Periago, Renata C. Diniz, Simone A. Pinto, Anna Yakovleva, Rodrigo Correa-Oliveira, David J. Diemert, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Due to the recent increased use of the McMaster (MM) fecal egg counting method for assessing benzimidazole drug efficacy for treating soil-transmitted helminth (STH) infections, the aim of the current study was to determine the operational value of including the MM method alongside the Kato-Katz (KK) fecal thick smear to increase the diagnostic sensitivity when STHs are co-endemic with trematode helminths (e.g., Schistosoma mansoni).

Methods

A cross-sectional study was conducted in school-aged children aged 4-18 years in the northeastern region of the State of Minas Gerais (Brazil), where Necator americanus, Ascaris lumbricoides, Trichuris trichiura, and S …

Lack Of Artemisinin Resistance In Plasmodium Falciparum In Uganda Based On Parasitological And Molecular Assays, Roland A. Cooper, Melissa D. Conrad, Quentin D. Watson, Stephanie J. Huezo, Harriet Ninsiima, Patrick Tumwebaze, Samuel L. Nsobya, Philip J. Rosenthal

Collected Faculty Scholarship

We evaluated markers of artemisinin resistance in Plasmodium falciparum isolated in Kampala in 2014. By standard in vitro assays, all isolates were highly sensitive to dihydroartemisinin (DHA). By the ring-stage survival assay, after a 6-h DHA pulse, parasitemia was undetectable in 40 of 43 cultures at 72 h. Two of 53 isolates had nonsynonymous K13-propeller gene polymorphisms but did not have the mutations associated with resistance in Asia. Thus, we did not see evidence for artemisinin resistance in Uganda.

Screening For G6pd Deficiency Among Neonates With Neonatal Jaundice Admitted To Tertiary Care Center: A Need In Disguise, Kishwer Kumar, Arjumand Sohaila, Shiyam Sunder Tikmani, Iqtidar Ahmed Khan, Anila Zafar

Department of Paediatrics and Child Health

This study was conducted to determine the association of Glucose-6-Phosphate Dehydrogenase (G-6-PD) deficiency among neonates admitted with jaundice at the neonatal intensive care unit, well baby nursery and neonatal step down nursery of the Aga Khan University Hospital, Karachi, Pakistan, from January to June 2010. A total of 205 neonates following the selection criteria were included. All selected neonates have their venous blood drawn, saved in EDTA bottle and sent to laboratory of The Aga Khan University Hospital (AKUH). The laboratory results of whether G-6-PD deficiency was present or not was recorded in the proforma. G-6-PD was deficient in 19 …

Acute Myocardial Infarction And Myocardial Ischemia-Reperfusion Injury: A Comparison, Satwat Hashmi, Suhail Al-Salam

Department of Biological & Biomedical Sciences

Myocardial infarction (MI) denotes the death of cardiac myocytes due to extended ischemia. Myocardial reperfusion is the restoration of coronary blood flow after a period of coronary occlusion. Reperfusion has the potential to salvage ischemic myocardium but paradoxically can cause injury, a phenomenon called as 'reperfusion injury' (IR). Standard histologic, immunohistochemical and Elisa techniques were used to study the histopathologic, oxidative, apoptotic and inflammatory changes in MI and IR. The IL-6 levels in the LV of the MI group were significantly raised as compared to the IR group (P=0.0008). Plasma IL-6 was also significantly increased in the MI group as …

Transcatheter Aortic Valve Replacement: A Physician-Patient's Story, Herbert L Fred

The Texas Heart Institute Journal

No abstract provided.

Prevalence Of A Chytrid Pathogen (Batrachochytrium Dendrobatidis) In Eastern Hellbender Salamanders In New York And Pennsylvania, Linxuan Wu

Biology Theses

Amphibian populations are currently declining globally. There are many possible causes for these declines, among which an emerging infectious disease, chytridiomycosis, has been implicated. Chytridiomycosis in the U.S.A. is mainly caused by the Batrachochytrium dendrobatidis. In this study, I used qPCR assays to detect the existence of this pathogen in the Eastern Hellbender (Cryptobranchus alleganiensis alleganiensis) populations in the Allegheny and Susquehanna River drainages of New York and Pennsylvania. Chytrid is most often tested by using skin swabs, but in this study, tail clips, dorsal skin, blood and eggs were tested as well. Batrachochytrium dendrobatidis was detected …

The Search For High-Impact Diagnostic And Management Tools For Low-And Middle-Income Countries: A Self-Powered Low-Cost Blood Pressure Measurement Device Powered By A Solid-State Vibration Energy Harvester, Onur Bilgen, John G. Kenerson, Muge Akpinar-Elci, Rebecca Hattery, Lisbet M. Hanson

Mechanical & Aerospace Engineering Faculty Publications

The World Health Organization has established recommendations for blood pressure measurement devices for use in low-resource venues, setting the triple A expectations of Accuracy, Affordability, and Availability. Because of issues related to training and assessment of proficiency, the pendulum has swung away from manual blood pressure devices and auscultatory techniques towards automatic oscillometric devices. As a result of power challenges in the developing world, there has also been a push towards semiautomatic devices that are not dependent on external power sources or batteries. Beyond solar solutions, disruptive technology related to solid-state vibrational energy harvesting may be the next iterative solution …

Ankyrin-B And Mtor Complex 1 In The Regulation Of Electrical Activities In The Heart, Henry C. Wu, Henry C. Wu

Dissertations and Theses (Open Access)

The mammalian target of rapamycin complex 1 (mTORC1) activity is paramount in the regulation of electrical activities in the brain and the heart. In the brain, the tumor suppressor gene TSC2 encodes the protein product tuberin that interacts with hamartin to form a heterodimer Tuberous Sclerosis Complex (TSC) that regulates mTORC1. When TSC2 is disrupted, mTORC1 activity becomes dysregulated resulting in abnormal electrical activities in the brain manifesting in the form of epileptic seizures. In the heart, mTORC1 activity is triggered by a sustained increase in hemodynamic pressure causing the heart to electrically remodel. A likely candidate serving as the …

Yap1 Expression Predicts Sensitivity To Dual Akt/P70s6k Inhibition In Ovarian And Uterine Malignancies, Rebecca A. Previs

Dissertations and Theses (Open Access)

Purpose: The PI3K/AKT/P70S6K pathway is an attractive therapeutic target in ovarian and uterine malignancies due to its high rate of dysregulation and key roles in tumor growth. Here, we examined the biological effects of MSC2363318A, which is a novel inhibitor of AKT1, AKT3, and P70S6K.

Experimental Design: Orthotopic murine models of ovarian and uterine cancer were utilized to study the effect of MSC2363318A on survival and regression. Moreover, in vitro experiments (MTT, Western blot analysis, plasmid transfection, and reverse phase protein array [RPPA]) were carried out to characterize underlying mechanisms and potential biomarkers of response.

Results: MSC2363318A decreased tumor growth …

Health-Related Quality Of Life In Children With Cancer, Tha'er Ghandi Almomani

Theses and Dissertations (ETD)

Health-related quality of life is an important phenomenon to measure in children undergoing treatment for cancer. However, the effects of different treatment modalities and cancer related factors over the duration of treatment have not been explored. To assess the effects of different child-, cancer-, and treatment-related factors, we analyzed a large sample of children undergoing curative treatment for 5 different childhood cancer diagnoses. These diagnostic groups were Hodgkin Lymphoma (HL), Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML), Osteosarcoma (OS), and Melanoma. We analyzed a sample of 710 patients across the five diagnostic groups over four time-points in treatment. These …

Adverse Effects Of Asparaginase In Pediatric Patients With Acute Lymphoblastic Leukemia, Chengcheng Liu

Theses and Dissertations (ETD)

Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer. Asparaginase is a critical treatment component for ALL. However, its use is complicated by adverse effects, such as hypersensitivity, osteonecrosis and pancreatitis.

Hypersensitivity to asparaginase typically requires discontinuation of current formulation and substitution with other formulations, but the differential diagnosis can be challenging, and the diagnostic utility of antibody tests is unclear. We comprehensively analyzed anti-Elspar (native E.coli asparaginase) IgG antibodies in 410 pediatric patients treated on an asparaginaseintensive front-line clinical trial. Of 169 patients (41.2%) who exhibited clinical allergy, 147 (87.0%) were positive for anti-Elspar antibody. Of …

Scarnas Regulate Splicing And Vertebrate Heart Development., Prakash Patil, Nataliya Kibiryeva, Tamayo Uechi, Jennifer A. Marshall, James E. O'Brien, Michael Artman, Naoya Kenmochi, Douglas C. Bittel

Manuscripts, Articles, Book Chapters and Other Papers

Alternative splicing (AS) plays an important role in regulating mammalian heart development, but a link between misregulated splicing and congenital heart defects (CHDs) has not been shown. We reported that more than 50% of genes associated with heart development were alternatively spliced in the right ventricle (RV) of infants with tetralogy of Fallot (TOF). Moreover, there was a significant decrease in the level of 12 small cajal body-specific RNAs (scaRNAs) that direct the biochemical modification of specific nucleotides in spliceosomal RNAs. We sought to determine if scaRNA levels influence patterns of AS and heart development. We used primary cells derived …

Impact Of Insulin Resistance On Neointimal Tissue Proliferation After 2nd-Generation Drug-Eluting Stent Implantation, Takaaki Komatsu, Isao Yaguchi, Sachiko Komatsu, Shiro Nakahara, Sayuki Kobayashi, Yoshihiko Sakai, Isao Taguchi

The Texas Heart Institute Journal

Percutaneous coronary intervention is established as an effective treatment for patients with ischemic heart disease; in particular, drug-eluting stent implantation is known to suppress in-stent restenosis. Diabetes mellitus is an independent risk factor for restenosis, so reducing insulin resistance is being studied as a new treatment approach. In this prospective study, we sought to clarify the factors associated with in-stent restenosis after percutaneous coronary intervention, and we evaluated the homeostasis model assessment of insulin resistance (HOMA-IR) index as a predictor of restenosis.

We enrolled 136 consecutive patients who underwent elective percutaneous coronary intervention at our hospital from February 2010 through …

Successful Use Of Therapeutic Hypothermia In A Pregnant Patient, Kevin N Oguayo, Ola O Oyetayo, David Stewart, Steven M Costa, Richard O Jones

The Texas Heart Institute Journal

Out-of-hospital cardiac arrest is a leading cause of death in the United States. Pregnant women are not immune to cardiac arrest, and the treatment of such patients can be difficult. Pregnancy is a relative contraindication to the use of therapeutic hypothermia after cardiac arrest.

A 20-year-old woman who was 18 weeks pregnant had an out-of-hospital cardiac arrest. Upon her arrival at the emergency department, she was resuscitated and her circulation returned spontaneously, but her score on the Glasgow Coma Scale was 3. After adequate family discussion of the risks and benefits of therapeutic hypothermia, a decision was made to initiate …

Primary Prevention Of Sudden Cardiac Death In Adults With Transposition Of The Great Arteries: A Review Of Implantable Cardioverter-Defibrillator Placement, Sandeep S Sodhi, Ari M Cedars

The Texas Heart Institute Journal

Transposition of the great arteries encompasses a set of structural congenital cardiac lesions that has in common ventriculoarterial discordance. Primarily because of advances in medical and surgical care, an increasing number of children born with this anomaly are surviving into adulthood. Depending upon the subtype of lesion or the particular corrective surgery that the patient might have undergone, this group of adult congenital heart disease patients constitutes a relatively new population with unique medical sequelae. Among the more common and difficult to manage are cardiac arrhythmias and other sequelae that can lead to sudden cardiac death. To date, the question …

Ultrasound Biomicroscopic Imaging For Interleukin-1 Receptor Antagonist-Inhibiting Atherosclerosis And Markers Of Inflammation In Atherosclerotic Development In Apolipoprotein-E Knockout Mice, Rong-Juan Li, Yan Sun, Qin Wang, Jiao Yang, Ya Yang, Li Song, Zheng Wang, Xiang-Hong Luo, Rui-Juan Su

The Texas Heart Institute Journal

We sought to validate the hypothesis that the development of atherosclerosis can be suppressed by the interleukin-1 receptor antagonist (IL-1Ra) in murine models of atherosclerosis in vivo, noninvasively seen by means of high-resolution ultrasound biomicroscopy, and we studied changes in inflammatory markers such as IL-1 and C-reactive protein (CRP) plasma levels in these models of atherosclerosis.

We divided IL-1Ra+/−/apolipoprotein-E (apoE)−/− and IL-1Ra+/+/apoE−/− mice into 2 age groups, used as atherosclerotic models. The control groups were age-matched IL-1Ra+/+/apoE+/+ mice. Plaque thickness was measured in the ascending aorta in short-axis images by means of ultrasound and histology. Plasma levels of IL-1 and …

Modified Maze Procedure For Atrial Fibrillation As An Adjunct To Elective Cardiac Surgery: Predictors Of Mid-Term Recurrence And Echocardiographic Follow-Up, Claudia Loardi, Francesco Alamanni, Fabrizio Veglia, Claudia Galli, Alessandro Parolari, Marco Zanobini

The Texas Heart Institute Journal

The radiofrequency maze procedure achieves sinus rhythm in 45%–95% of patients treated for atrial fibrillation. This retrospective study evaluates mid-term results of the radiofrequency maze—performed concomitant to elective cardiac surgery—to determine sinus-rhythm predictive factors, and describes the evolution of patients' echocardiographic variables.

From 2003 through 2011, 247 patients (mean age, 64 ± 9.5 yr) with structural heart disease (79.3% mitral disease) and atrial fibrillation underwent a concomitant radiofrequency modified maze procedure. Patients were monitored by 24-hour Holter at 3, 6, 12, and 24 months, then annually. Eighty-four mitral-valve patients underwent regular echocardiographic follow-up. Univariate and multivariate analysis for risk factors …

Numerical Chromosomal Instability Mediates Susceptibility To Radiation Treatment, Samuel F. Bakhoum, Lilian Kabeche, Matthew D. Wood, Christopher D. Laucius

Dartmouth Scholarship

The exquisite sensitivity of mitotic cancer cells to ionizing radiation (IR) underlies an important rationale for the widely used fractionated radiation therapy. However, the mechanism for this cell cycle-dependent vulnerability is unknown. Here we show that treatment with IR leads to mitotic chromosome segregation errors in vivo and long-lasting aneuploidy in tumour-derived cell lines. These mitotic errors generate an abundance of micronuclei that predispose chromosomes to subsequent catastrophic pulverization thereby independently amplifying radiation-induced genome damage. Experimentally suppressing whole-chromosome missegregation reduces downstream chromosomal defects and significantly increases the viability of irradiated mitotic cells. Further, orthotopically transplanted human glioblastoma tumours in which …

Amikacin Concentrations Predictive Of Ototoxicity In Multidrug-Resistant Tuberculosis Patients, Chawangwa Modongo, Jotam G. Pasipanodya, Nicola M. Zetola, Scott M. Williams

Dartmouth Scholarship

Aminoglycosides, such as amikacin, are used to treat multidrug-resistant tuberculosis. However, ototoxicity is a common problem and is monitored using peak and trough amikacin concentrations based on World Health Organization recommendations. Our objective was to identify clinical factors predictive of ototoxicity using an agnostic machine learning method. We used classification and regression tree (CART) analyses to identify clinical factors, including amikacin concentration t

hresholds that pre- dicted audiometry-confirmed ototoxicity among 28 multidrug-resistant pulmonary tuberculosis patients in Botswana. Amika- cin concentrations were measured for all patients. The quantitative relationship between predictive factors and the probability of ototoxicity were then identified using …

Addressing Therapeutic Options For Ebola Virus Infection In Current And Future Outbreaks, Azizul Haque, Didier Hober, Joel Blondiaux

Dartmouth Scholarship

Ebola virus can cause severe hemorrhagic disease with high fatality rates. Currently, no specific therapeutic agent or vaccine has been approved for treatment and prevention of Ebola virus infection of humans. Although the number of Ebola cases has fallen in the last few weeks, multiple outbreaks of Ebola virus infection and the likelihood of future exposure highlight the need for development and rapid evaluation of pre- and postexposure treatments. Here, we briefly review the existing and future options for anti-Ebola therapy, based on the data coming from rare clinical reports, studies on animals, and results from in vitro models. We …

Isis Pharmaceuticals Launches Historic Clinical Trial To Silence Huntington's Disease Gene, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Macrolide-Resistant Mycoplasma Pneumoniae, United States, Xiaotian Zheng, Stella Lee, Rangaraj Selvarangan, Xuan Qin, Yi Wei Tang, Jeffrey Stiles, Tao Hong, Kathleen Todd, Amy E. Ratliff, Donna M. Crabb, Li Xiao, T. Prescott Atkinson, Ken B. Waites

Manuscripts, Articles, Book Chapters and Other Papers

© 2015, Centers for Disease Control and Prevention (CDC). All rights reserved.

Macrolide-resistant Mycoplasma pneumoniae (MRMP) is highly prevalent in Asia and is now being reported from Europe. Few data on MRMP are available in the United States. Using genotypic and phenotypic methods, we detected high-level MRMP in 13.2% of 91 M. pneumoniae–positive specimens from 6 US locations.