Medicine and Health Sciences Commons^™

Correcting Glucose-6-Phosphate Dehydrogenase Deficiency With A Small-Molecule Activator, Sunhee Hwang, Karen Mruk, Simin Rahighi, Andrew G. Raub, Che-Hong Chen, Lisa E. Dorn, Naoki Horikoshi, Soichi Wakatsuki, James K. Chen, Daria Mochly-Rosen

Pharmacy Faculty Articles and Research

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, one of the most common human genetic enzymopathies, is caused by over 160 different point mutations and contributes to the severity of many acute and chronic diseases associated with oxidative stress, including hemolytic anemia and bilirubin-induced neurological damage particularly in newborns. As no medications are available to treat G6PD deficiency, here we seek to identify a small molecule that corrects it. Crystallographic study and mutagenesis analysis identify the structural and functional defect of one common mutant (Canton, R459L). Using high-throughput screening, we subsequently identify AG1, a small molecule that increases the activity of the wild-type, the …

Eye Tissue Regeneration: Seam As A Cure For Prevalent Eye Disease, Molly Bute

Biology: Student Scholarship & Creative Works

SEAM (Self-formed ectodermal autonomous multizone) is a form of eye tissue regeneration discovered by Japanese scientists in 2016. This tissue regeneration encompasses tissues from all areas of the human eye. The SEAM forms tissues using stem cells, induced pluripotent stem cells were used in the first study, and produces four concentric zones. The SEAM that has been created was shown to cure corneal blindness in animal models, and has the potential to cure a multitude of human eye diseases in the future.

Germline Sdhb And Sdhd Mutations In Pheochromocytoma And Paraganglioma Patients, Yiqiang Huang, Lin-Ang Wang, Qiubo Xie, Jian Pang, Luofu Wang, Yuting Yi, Jun Zhang, Yao Zhang, Rongrong Chen, Weihua Lan, Dianzheng Zhang, Jun Jiang

PCOM Scholarly Works

Pheochromocytoma and paragangliomas (PCC/PGL) are neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and sympathetic/parasympathetic ganglia, respectively. Of clinical relevance regarding diagnosis is the highly variable presentation of symptoms in PCC/PGL patients. To date, the clear-cut correlations between the genotypes and phenotypes of PCC/PGL have not been entirely established. In this study, we reviewed the medical records of PCC/PGL patients with pertinent clinical, laboratory and genetic information. Next-generation sequencing (NGS) performed on patient samples revealed specific germline mutations in the SDHB (succinate dehydrogenase complex iron-sulfur subunit B) and SDHD（succinate dehydrogenase complex subunit D) genes and these mutations …

Expanding Indications Of Endovascular Aortic Aneurysm Repair, Zia Ur Rehman

Section of Cardiothoracic Surgery

No abstract provided.

Expanding Indications Of Endovascular Aortic Aneurysm Repair, Zia Ur Rehman

Section of Cardiothoracic Surgery

No abstract provided.

Expanding Indications Of Endovascular Aortic Aneurysm Repair, Zia Ur Rehman

Section of Cardiothoracic Surgery

No abstract provided.

Internalized Hiv Stigma, Art Initiation And Hiv-1 Rna Suppression In South Africa: Exploring Avoidant Coping As A Longitudinal Mediator, Valerie A. Earnshaw, Laura M. Bogart, Jean-Philippe Laurenceau, Brian T. Chan, Brendan G. Maughan-Brown, Janan Dietrich, Ingrid Courtney, Gugu Tshabalala, Catherine Orrell, Glenda E. Gray, David Bangsberg, Ingrid T. Katz

OHSU-PSU School of Public Health Faculty Publications and Presentations

Introduction: Cross‐sectional evidence suggests that internalized HIV stigma is associated with lower likelihoods of antiretroviral therapy (ART) initiation and HIV‐1 RNA suppression among people living with HIV (PLWH). This study examined these associations with longitudinal data spanning the first nine months following HIV diagnosis and explored whether avoidant coping mediates these associations.

Methods: Longitudinal data were collected from 398 South African PLWH recruited from testing centres in 2014 to 2015. Self‐report data, including internalized stigma and avoidant coping (denying and distracting oneself from stressors), were collected one week and three months following HIV diagnosis. ART initiation at six months and …

Pediatric Cancers: Development And Treatment Methods, Makayla M. Walker

Student Publications

Pediatric cancers are cancers that develop in kids and adolescents ages 0-19. Pediatric cancers usually develop in three ways: through inherited gene mutations, parental exposure to toxins, and acquired gene mutations. While cancer can affect children and adults alike, treatment becomes more difficult for children due to their physical predevelopment stages. Therefore, it is important to discuss all methods of treatment when dealing with a particular pediatric cancer in order to choose the most effective method.

A Brief Report Of Immunohistochemical Markers To Identify Aggressive Hepatoblastoma., Vivekanand Singh, Michelle Manalang, Meenal Singh, Udayan Apte

Manuscripts, Articles, Book Chapters and Other Papers

Hepatoblastoma (HB) is the most common malignant liver tumor in children. Although survival of patients has improved significantly over the last 2 decades, a significant number of patients do not respond to standard chemotherapy. We conducted a pilot study to understand if there was immunophenotypic difference between tumors that respond well to chemotherapy versus that do not. We selected 10 cases of HB from children presenting at our hospital. All patients had initial tissue diagnosis, underwent chemotherapy followed by surgical resection. The cases were divided into 2 groups: aggressive group with 5 cases (all of which had a poor response …

Regeneration Of Neurotransmission Transcriptome In A Model Of Epileptic Encephalopathy After Antiinflammatory Treatment, Dumitru Iacobas, Libor Velisek

NYMC Faculty Publications

Inflammation is an established etiopathogenesis factor of infantile spasms (IS), a therapy-resistant epileptic syndrome of infancy. We investigated the IS-associated transcriptomic alterations of neurotransmission in rat hypothalamic arcuate nucleus, how they are corrected by antiinflamatory treatments and whether there are sex differences. IS was triggered by repeated intraperitoneal administration of N-methyl-D-aspartic acid following anti-inflammatory treatment (adreno-cortico-tropic-hormone (ACTH) or PMX53) or normal saline vehicle to prenatally exposed to betamethasone young rats. We found that treatments with both ACTH and PMX53 resulted in substantial recovery of the genomic fabrics of all types of synaptic transmission altered by IS. While ACTH represents the …

Ion-Sensitive Field-Effect Transistors With Micropillared Gates For Measuring Cell Ion Exchange At Molecular Levels, Mohammad G. Abdallah, Rayan Khan, Christian Garcia, Young-Tae Kim, Samir M. Iqbal

Electrical and Computer Engineering Faculty Publications

The detection of small concentrations of cancer cells before cancer takes over the primary organ completely, or metastasizes to other areas of the body is important for early screening of cancer. One approach to address cancer early screening is through cell ion exchange bioelectricity, which characterizes voltage potential in non-neuronal cells to regulate shape changing, proliferation, differentiation, migration, and cancer formation. Herein, novel ion-sensitive field-effective transistor (ISFET) modality is shown to measure cell behavior during the change of cell properties at molecular levels. ISFETs produce low resistance signals and consume low power. The small size of ISFETs enables miniature diagnosis …

Unpacking Generation Hd1, The Roche Phase 3 Huntington's Disease Clinical Trial, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Mrsa In The United States, Sweden, And Syria, Derek J. Lillestolen

Montview Journal of Research & Scholarship

Methicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic pathogen that is resistant to many broad and narrow-spectrum antibiotics commonly used in the treatment of S. aureus. There has been much fanfare about MRSA, receiving nicknames like “superbug” because of its varying degrees of resistance to the most common broad and narrow-spectrum antibiotics such as penicillin, oxacillin, methicillin and amoxicillin (2). The reality, however, is that MRSA is still susceptible to certain antibiotics and can be treated effectively. This study displays the factors which help and hurt MRSA treatments. There is shown a strong link between the prescription of broad-spectrum antibiotics …

Epidemiology Of Diabetic Foot Infection In The Metro-Detroit Area With A Focus On Independent Predictors For Pathogens Resistant To Recommended Empiric Antimicrobial Therapy, Oryan Henig, Jason M. Pogue, Raymond Cha, Paul E. Kilgore, Umar Hayat, Mahmoud Ja'ara, Raza Muhamad Ali, Salman Mahboob, Rahul Pansare, Kathryn Deeds, Bushra Joarder, Hyndavi Kandala, Sorabh Dhar, Keith S. Kaye

Department of Pharmacy Practice

Background. The polymicrobial nature of diabetic foot infection (DFI) and the emergence of antimicrobial resistance have complicated DFI treatment. Current treatment guidelines for deep DFI recommend coverage of methicillin-resistant Staphylococcus aureus (MRSA) and susceptible Enterobacteriaceae. This study aimed to describe the epidemiology of DFI and to identify predictors for DFI associated with multidrug-resistant organisms (MDROs) and pathogens resistant to recommended treatment (PRRT).

Methods. Adult patients admitted to Detroit Medical Center from January 2012 to December 2015 with DFI and positive cultures were included. Demographics, comorbidities, microbiological history, sepsis severity, and antimicrobial use within 3 months before DFI were obtained …

Hand Issues On Scleroderma Patients, Ana Font Hernandez

Publications and Research

Based on the design of a 3D-printed spoon prototype, we surveyed scleroderma patients about the device's value. 75% of patients mentioned having problems on their hands due to scleroderma. 85% of patients said their hand form changed because of the disease. Answers to the frequency or speed of the changes provide inconclusive results. The 3D printing technology has the potential to solve specific issues scleroderma patients face in their daily lives. Nevertheless, further research is needed to fully understand how hands shape change over time.

Editorial: Ion Channel Trafficking And Cardiac Arrhythmias, Marcel A. G. Van Der Heyden, Brian P. Delisle, Hugues Abriel

Physiology Faculty Publications

No abstract provided.

Griffithsin Carrageenan Fast Dissolving Inserts Prevent Shiv Hsv-2 And Hpv Infections In Vivo, Nina Derby, Manjari Lal, Meropi Aravatinou, Larisa Kizima, Patrick Barnable, Axia Rodriguez, Manshun Lai, Asa Wesenberg, Shweta Ugaonkar, Keith Levendosky, Olga Mizenina, Kyle Kleinbeck, Jeffrey D. Lifson, M. Melissa Peet, Zachary Lloyd, Michael Benson, Walid Heneine, Barry R. O'Keefe, Melissa Robbiani, Elena Martinelli, Brooke Grasperge, James Blanchard, Agegnehu Gettie, Natalia Teleshova, José Fernández-Romero, Thomas M. Zydowsky

Publications and Research

Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) strategies with proven in vivo efficacy rely on antiretroviral drugs, creating the potential for drug resistance and complicated treatment options in individuals who become infected. Moreover, ondemand products are currently missing from the PrEP development portfolio. Griffithsin (GRFT) is a non-antiretroviral HIV entry inhibitor derived from red algae with an excellent safety profile and potent activity in vitro. When combined with carrageenan (CG), GRFT has strong activity against herpes simplex virus-2 (HSV-2) and human papillomavirus (HPV) in vitro and in vivo. Here, we report that GRFT/CG in a freeze-dried fast dissolving insert (FDI) …

The Chapman Bone Algorithm: A Diagnostic Alternative For The Evaluation Of Osteoporosis, Elise Levesque, Anton Ketterer, Wajiha Memon, Cameron James, Noah Barrett, Cyril Rakovski, Frank Frisch

Mathematics, Physics, and Computer Science Faculty Articles and Research

Osteoporosis is the most common metabolic bone disease and goes largely undiagnosed throughout the world, due to the inaccessibility of DXA machines. Multivariate analyses of serum bone turnover markers were evaluated in 226 Orange County, California, residents with the intent to determine if serum osteocalcin and serum pyridinoline cross-links could be used to detect the onset of osteoporosis as effectively as a DXA scan. Descriptive analyses of the demographic and lab characteristics of the participants were performed through frequency, means and standard deviation estimations. We implemented logistic regression modeling to find the best classification algorithm for osteoporosis. All calculations and …

De-Airing Method Of An Axial Flow Left Ventricular Assist Device Influences Post-Operative Lactate Dehydrogenase Levels: A Possible Explanation For Some Episodes Of Pump Thrombosis, Daizo Tanaka, Saif Rizvi, Andrew Boyle, Md, John W..C. Entwistle

The VAD Journal

Background

Pump thrombosis (PT) is a relatively uncommon but serious complication of a left ventricular assist device (LVAD). We believe that de-airing of the HeartMate II (HMII) with the pump turned on and a clamp across the outflow graft may lead to early thrombus formation due to heat generation on the bearings.

Methods

Patients who underwent HMII implantation from November 2012 to February 2016 were retrospectively reviewed. Patients were separated into two groups depending on the timing of removing the clamp from the outflow graft. Patients in Group 1 underwent de-airing by turning on the pump with the vascular clamp …

Routine, Opt-Out Hiv Testing In A Rural Emergency Department, Ciarra Jm Dortche

9th Annual Rural HIV Research & Training Conference (2014-2019) (Archived)

There are approximately 1,800 people living with HIV in eastern North Carolina and are unaware of their infection. A decade ago, the Centers for Disease Control and Prevention (CDC) issued revised recommendations to routinely test for HIV in various settings, including emergency departments. We used those guidelines to test adults, treat those unaware of their infection, and re-link others to care.

Astrocyte Activation And The Calcineurin/Nfat Pathway In Cerebrovascular Disease, Susan D. Kraner, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Calcineurin (CN) is a Ca²⁺/calmodulin-dependent protein phosphatase with high abundance in nervous tissue. Though enriched in neurons, CN can become strongly induced in subsets of activated astrocytes under different pathological conditions where it interacts extensively with the nuclear factor of activated T cells (NFATs). Recent work has shown that regions of small vessel damage are associated with the upregulation of a proteolized, highly active form of CN in nearby astrocytes, suggesting a link between the CN/NFAT pathway and chronic cerebrovascular disease. In this Mini Review article, we discuss CN/NFAT signaling properties in the context of vascular disease and …

Justice Served Fresh: Associations Between Food Insecurity, Community Gardening, And Property Value, Micajah Daniels, Courtney Coughenour Ph.D

McNair Poster Presentations

Numerous stakeholders in Nevada have used a variety of efforts to combat the growth of food insecurity facing Nevadans. The purpose of this research project is to understand the association between food insecurity, community gardens, and property value. Following the wealth of scholarship on these topics and data collected from community garden agencies in Southern Nevada, the research questions for this project include: (1) Where are community gardens located in SNV? (2) What efforts community gardens agencies are doing to address food insecurity (most interested in their efforts using community gardens)? (3) What are the perceptions of supports and barriers …

Roche Phase 3 Clinical Trial For Huntington’S Disease Gene-Slicing Drug To Enroll Volunteers In Early 2019, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Myocyte [Na+]I Dysregulation In Heart Failure And Diabetic Cardiomyopathy, Sanda Despa

Pharmacology and Nutritional Sciences Faculty Publications

By controlling the function of various sarcolemmal and mitochondrial ion transporters, intracellular Na⁺ concentration ([Na⁺]_i) regulates Ca²⁺ cycling, electrical activity, the matching of energy supply and demand, and oxidative stress in cardiac myocytes. Thus, maintenance of myocyte Na⁺ homeostasis is vital for preserving the electrical and contractile activity of the heart. [Na⁺]_i is set by the balance between the passive Na⁺ entry through numerous pathways and the pumping of Na⁺ out of the cell by the Na⁺/K⁺-ATPase. This equilibrium is perturbed in heart failure, …

In Vivo Brainstem Imaging In Alzheimer’S Disease: Potential For Biomarker Development, David J. Braun, Linda J. Van Eldik

Neuroscience Faculty Publications

The dearth of effective treatments for Alzheimer’s disease (AD) is one of the largest public health issues worldwide, costing hundreds of billions of dollars per year. From a therapeutic standpoint, research efforts to date have met with strikingly little clinical success. One major issue is that trials begin after substantial pathological change has occurred, and it is increasingly clear that the most effective treatment regimens will need to be administered earlier in the disease process. In order to identify individuals within the long preclinical phase of AD who are likely to progress to dementia, improvements are required in biomarker development. …

Brain Endothelial Erythrophagocytosis And Hemoglobin Transmigration Across Brain Endothelium: Implications For Pathogenesis Of Cerebral Microbleeds, Rudy Chang, Juan Castillo, Alexander C. Zambon, Tatiana B. Krasieva, Mark J. Fisher, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Peripheral endothelial cells are capable of erythrophagocytosis, but data on brain endothelial erythrophagocytosis are limited. We studied the relationship between brain endothelial erythrophagocytosis and cerebral microhemorrhage, the pathological substrate of MRI-demonstrable cerebral microbleeds. To demonstrate the erythrophagocytic capability of the brain endothelium, we studied the interactions between brain endothelial cells and red blood cells exposed to oxidative stress in vitro, and developed a new in vitro cerebral microbleeds model to study the subsequent passage of hemoglobin across the brain endothelial monolayer. Using multiple approaches, our results show marked brain endothelial erythrophagocytosis of red blood cells exposed to oxidative stress compared …

Genetic Determinants Of Telomere Length In African American Youth, Andrew M. Zeiger, Marquitta J. White, Celeste Eng, Sam S. Oh, Jonathan Witonsky, Pagé C. Goddard, Maria G. Contreras, Jennifer R. Elhawary, Donglei Hu, Angel C. Y. Mak, Eunice Y. Lee, Kevin L. Keys, Lesly-Anne Samedy, Oona Risse Adams, Joaquín Magaña, Scott Huntsman, Sandra Salazar, Adam Davis, Kelley Meade, Emerita Brigino-Buenaventura, Michael A. Lenoir, Harold J. Farber, Kirsten Bibbins-Domingo, Luisa N. Borrell, Esteban G. Burchard

Publications and Research

Telomere length (TL) is associated with numerous disease states and is affected by genetic and environmental factors. However, TL has been mostly studied in adult populations of European or Asian ancestry. These studies have identified 34 TL-associated genetic variants recently used as genetic proxies for TL. The generalizability of these associations to pediatric populations and racially diverse populations, specifically of African ancestry, remains unclear. Furthermore, six novel variants associated with TL in a population of European children have been identified but not validated. We measured TL from whole blood samples of 492 healthy African American youth (children and adolescents between …

Interfering With Dna Decondensation As A Strategy Against Mycobacteria, Enzo M. Scutigliani, Edwin R. Scholl, Anita E. Grootemaat, Sadhana Khanal, Jakub A. Kochan, Przemek M. Krawczyk, Eric A. Reits, Atefeh Garzan, Huy X. Ngo, Keith D. Green, Sylvie Garneau-Tsodikova, Jan M. Ruijter, Henk A. Van Veen, Nicole N. Van Der Wel

Pharmaceutical Sciences Faculty Publications

Tuberculosis is once again a major global threat, leading to more than 1 million deaths each year. Treatment options for tuberculosis patients are limited, expensive and characterized by severe side effects, especially in the case of multidrug-resistant forms. Uncovering novel vulnerabilities of the pathogen is crucial to generate new therapeutic strategies. Using high resolution microscopy techniques, we discovered one such vulnerability of Mycobacterium tuberculosis. We demonstrate that the DNA of M. tuberculosis can condense under stressful conditions such as starvation and antibiotic treatment. The DNA condensation is reversible and specific for viable bacteria. Based on these observations, we hypothesized …

Compound Heterozygosity For A Whole Gene Deletion And P.R124c Mutation In Cyp21a2 Causing Nonclassic Congenital Adrenal Hyperplasia, Hamza Nasir, Syed Ibaad Ali, N Haque, Stefan K. Grebe, Salman Kirmani

Section of Diabetes, Endocrinology and Metabolism

We present a family with 2 members who received long-term steroid treatment for presumed classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, until molecular testing revealed nonclassic CAH, not necessarily requiring treatment. A 17-year-old male presented to our clinic on glucocorticoid and mineralocorticoid treatment for classic CAH. He was diagnosed at 4 years of age based on mild-moderate elevations of 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH), but without evidence of precocious adrenarche/puberty. Due to his diagnosis, his clinically asymptomatic 3-year-old sister was tested and also found to have elevated ACTH and 17-OHP levels and was started on glucocorticoids for …

Men’S Health In Industries: Plastic Plant Pollution And Prevalence Of Pre-Diabetes And Type 2 Diabetes Mellitus, Sultan Ayoub Meo, Faris Jamal Almutairi, Majed Mohammed Alasbali, Turki Badr Alqahtani, Saad Saeed Almutairi, Rakan Abdulaziz Albuhayjan, Fawziah Al Rouq, Naseer Ahmed

Department of Biological & Biomedical Sciences

Plastic production is prominently increasing and its pollution is an emerging environmental global health concern. This study aimed to investigate the occurrence of pre-diabetes and type 2 diabetes mellitus (T2DM) among nonsmoking plastic industry workers. Three hundred and forty volunteers male plastic industry workers were interviewed after medical history and examination; finally, 278 nonsmoking plastic industry workers were selected. The mean age for the participants was 38.03 ± 10.86 years and body mass index was 25.52 ± 3.15 (kg/m)². The plastic industry workers had been exposed to plastic plant pollution for 8 hr daily, 6 days in a …