Medicine and Health Sciences Commons^™

Classification Models Of Idiopathic Pulmonary Fibrosis Patients, Mohammed Alqawba, Luis R. Rodriguez, Norou Diawara, Rebecca T. Beuschel, Maryann Kaler, Amisha V. Barochia, Stewart J. Levine, Steven D. Nathan, Geraldine Grant

Mathematics & Statistics Faculty Publications

Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal interstitial lung disease with no current cure. Progression of IPF is difficult to predict as the clinical course can be highly variable and range from a rapidly deteriorating state to a relatively stable state, or may be characterized by a slow progressive decline. Therefore, the need for an accurate diagnosis and improved tools for monitoring and managing IPF is of paramount importance, all for understanding the mitochondrial structure and the function played in the IPF. Mitochondrial DNA copy number (MtDCN) has been correlated with mortality in IPF patients and is a …

Acute Lymphoblastic Leukemia Presenting Initially As Spinal Cord Compression: When Chemotherapy Alone Is Enough, Albert Jang, Kallie N Kram, Scott N Berger, Mahmoud R Gaballa, Lee B Lu, David R Dunaway, Courtney N Miller-Chism

Faculty, Staff and Students Publications

Spinal cord compression (SCC) is a rare initial presentation and complication of acute lymphoblastic leukemia (ALL) with nearly all reported cases occurring in the pediatric population. We report a 38-year-old previously healthy man who presented with acute on chronic lower back pain, gait instability, urinary retention, and severe thrombocytopenia. Radiologic examination revealed two soft tissue masses of the thoracic spine associated with compression fractures causing spinal canal narrowing and cord compression. Bone marrow biopsy confirmed the diagnosis of ALL. Immediate initiation of high-dose corticosteroids and systemic chemotherapy resolved the patient's symptoms without radiation therapy or surgical intervention. After two courses …

Spironolactone In Pulmonary Arterial Hypertension: Results Of A Cross-Over Study, Zeenat Safdar, Adaani Frost, Arya Basant, Anita Deswal, E O'Brian Smith, Mark Entman

Faculty, Staff and Students Publications

The renin–angiotensin–aldosterone system is implicated in the pathophysiology of pulmonary arterial hypertension. We undertook this study to determine the effects of spironolactone, a mineralocorticoid receptor blocker, on collagen metabolism in pulmonary arterial hypertension patients. After obtaining institutional review board approval and informed consent, 42 pulmonary arterial hypertension patients were prospectively enrolled and 35 patients completed the 16-week randomized double-blinded crossover clinical trial. Subjects received 50 mg spironolactone or placebo and at the end of week 8, treatment arm was switched. Circulating levels of collagen biomarkers, brain natriuretic peptide, and aldosterone levels were measured, and six-minute walk distance, liver function tests, …

Metaproteomic Analysis Of Human Gut Microbiome In Digestive And Metabolic Diseases, Sheng Pan, Ru Chen

Faculty, Staff and Students Publications

Metaproteomics, as a subfield of proteomics, has quickly emerged as a pivotal tool for global characterization of a microbiome system at a functional level. It has been increasingly applied in studying human digestive and metabolic diseases, and provides information-rich data to identify the dysbiosis of human gut microbiome related to healthy or disease states to elucidate the molecular events underlying host-microbiota interplays. While significant technical challenges still exist, this emerging technology has been demonstrated to provide essential information in interrogating functional changes in the human gut microbiome, complementary to metagenomics and metatranscriptomics. This chapter overviews the overall metaproteomic work flow …

Extracellular Mitochondria Released From Traumatized Brains Induced Platelet Procoagulant Activity, Zilong Zhao, Yuan Zhou, Tristan Hilton, Fanjian Li, Cha Han, Li Liu, Hengjie Yuan, Ying Li, Xin Xu, Xiaoping Wu, Fangyi Zhang, Perumal Thiagarajan, Andrew Cap, Fu-Dong Shi, Jianning Zhang, Jing-Fei Dong

Faculty, Staff and Students Publications

Coagulopathy often develops soon after acute traumatic brain injury and its cause remains poorly understood. We have shown that injured brains release cellular microvesicles that disrupt the endothelial barrier and induce consumptive coagulopathy. Morphologically intact extracellular mitochondria accounted for 55.2% of these microvesicles, leading to the hypothesis that these extracellular mitochondria are metabolically active and serve as a source of oxidative stress that activates platelets and renders them procoagulant. In testing this hypothesis experimentally, we found that the extracellular mitochondria purified from brain trauma mice and those released from brains subjected to freeze-thaw injury remained metabolically active and produced reactive …

Lisinopril-Induced Angioedema In A Patient With Plasma Prekallikrein Deficiency, Swapan K Dasgupta, Stefanie Rivera, Perumal Thiagarajan

Faculty, Staff and Students Publications

Angiotensin-converting enzyme (ACE) inhibitors are extensively prescribed to treat patients with hypertension, congestive heart failure, and diabetic nephropathy. A small fraction of these patients (approximately 0.7%) develop angioedema, manifested by swelling of the lips and oropharynx. Angioedema of oropharynx is a medical emergency that can lead to asphyxiation and death. The angioedema is due to bradykinin generated from high molecular weight kininogen by kallikrein, which is derived from plasma prekallikrein by action of the factor XIIa, factor Xia, or prolylcarboxypeptidase. Bradykinin induces vasodilation and increased vascular permeability. ACE is the major degrading enzyme of bradykinin in the intravascular department. ACE …

Hypogonadism, Type-2 Diabetes Mellitus, And Bone Health: A Narrative Review, Vittoria Russo, Rui Chen, Reina Armamento-Villareal

Faculty, Staff and Students Publications

One of the complications from chronic hyperglycemia and insulin resistance due to type 2 diabetes mellitus (T2DM) on the hypothalamic-pituitary-gonadal axis in men is the high prevalence of hypogonadotropic hypogonadism (HH). Both T2DM and hypogonadism are associated with impaired bone health and increased fracture risk but whether the combination results in even worse bone disease than either one alone is not well-studied. It is possible that having both conditions predisposes men to an even greater risk for fracture than either one alone. Given the common occurrence of HH or hypogonadism in general in T2DM, a significant number of men could …

Sirt3 Promotes Lipophagy And Chaperon-Mediated Autophagy To Protect Hepatocytes Against Lipotoxicity, Tian Zhang, Jingxin Liu, Shengnan Shen, Qiang Tong, Xiaojun Ma, Ligen Lin

Faculty, Staff and Students Publications

Lipophagy is a lysosomal lipolytic pathway that complements the actions of cytosolic neutral lipases. Chaperon-mediated autophagy (CMA) triggers lipid droplets (LDs) breakdown, to initiate lipolysis via either cytosolic lipases or macroautophagy. SIRT3, a mitochondrial NAD+-dependent deacetylase, regulates the acetylation status and activity of many substrates involving in energy metabolism. However, the role of SIRT3 in regulating lipophagy is controversial. The current study showed that SIRT3 expression was decreased and the macroautophagy flux was blocked in the primary hepatocytes from high-fat diet fed mice and P/O (palmitic acid and oleic acid mixture) treated AML12 mouse hepatocytes, compared with the corresponding controls. …

Vaccines And Ip Preparedness In The Coronavirus Outbreak, Ana Santos Rutschman

All Faculty Scholarship

The COVID-19 pandemic has shed renewed light on the importance of research and development (R&D) on biopharmaceutical products needed to prevent or lessen the burden posed by outbreaks of infectious diseases. Among these, the need for new vaccines has become of paramount importance. While a race to develop different types of vaccines unfolds at unusual speed, there are still significant shortcomings in the ecosystem that leads to the production and dissemination of vaccines targeting infectious diseases like COVID-19.

Reply To Lipworth Et Al., Angela M. Moran, Sanjay Ramakrishnan, Catherine A. Borg, Clare M. Connolly, Simon Couillard, Christine M. Mwasuku, Ian D. Pavord, Timothy S.C. Hinks, Lauri Lehtimӓki

Research outputs 2014 to 2021

We thank Dr. Lipworth and colleagues for their interest in our work published recently in the Journal (1). They rightly point out that the biology of asthma attacks is more complex than blood eosinophils alone and that corticosteroids have a wide range of other potentially relevant antiinflammatory effects. However, local treatment with inhaled corticosteroids (ICS) is usually the mainstay of patients with frequent eosinophilic exacerbations, and therefore in the great majority of patients, the key question is what oral corticosteroids (OCS) add to ICS in an acute attack (2) and whether this effect is seen with benralizumab. We suggest that …

The Impact Of Singing On Pulmonary Function And Quality Of Life In Patients With Muscular Dystrophy, Mia Simonette

Theses : Honours

Muscular dystrophy is a congenital disorder that results in progressive deterioration of muscle strength and function. The genetic disorder is caused by the absence of dystrophin protein which helps to keep muscle cells together, the absence of this protein causes muscles to become weak and fragile. Despite impairment of motor function and muscle strength, a major issue is the progressive impact on the respiratory muscles. Weak pulmonary function can lead to secondary issues such as atelectasis, decreased lung compliance, repeated infections, ineffective cough and ventilation-perfusion during sleep1. Respiratory failure is said to be the most common cause of death in …

Quantifying The Heterogeneity Of The Immunoglobulin G N-Glycome In An Ageing Australian Population: The Busselton Healthy Ageing Study, Alyce Russell

Theses: Doctorates and Masters

The use of immunoglobulin G N-glycomics to study chronic non-communicable disorders and other complex phenotypes emerged following the Human Genome Project. The consortium discovered that most phenotypes were too complex to be explained by genetics alone. Thus, the biological importance of epigenetics was recognised; heritable modifications to gene expression rather than the genome itself. Nglycosylation is a form of epigenetic regulation known as a post-translational modification. It stabilises the immunoglobulin G structure and alters downstream responses elicited by the antibody and is extensively studied as a candidate biomarker in the post-genomic era.

The N-glycosylation of immunoglobulin G itself is complex, …

Use Of Pefloxacin As A Surrogate Marker To Detect Ciprofloxacin Susceptibility In Salmonella Enterica Serotypes Typhi And Paratyphi A, Safia Moin, Mohammad Zeeshan, Sidra Laiq, Ahmed Raheem, Afia Zafar

Department of Pathology and Laboratory Medicine

Objective: To determine the use of pefloxacin as a surrogate marker to detect fluoroquinolone (ciprofloxacin) susceptibility against Salmonella enterica serotypes Typhi and Paratyphi A.
Methods: The prospective, descriptive cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, from September 2016 to March 2018, and comprised Salmonella Typhi and Paratyphi A isolates of blood cultures. Disk susceptibility tests and broth microdilution to test minimum inhibitory concentration were performed as per standard guidelines. Data was analysed using SPSS 21.
Results: Of the 138 isolates, 91(66%) were intermediate resistant to ciprofloxacin but were resistant to pefloxacin, 42(30%) were resistant to both …

The Mosaic Of Coronavirus Vaccine Development: Systemic Failures In Vaccine Innovation, Ana Santos Rutschman

All Faculty Scholarship

Scientists are racing to develop vaccines against the novel coronavirus. While some vaccine candidates may enter the market in record time, the current vaccine innovation ecosystem exposes governance lacunas at both the international and domestic levels.

Structural Discrimination In Covid-19 Workplace Protections, Ruqaiijah Yearby, Seema Mohapatra

All Faculty Scholarship

Workers, who are being asked to risk their health by working outside their homes during the COVID-19 pandemic, need adequate hazard compensation, safe workplace conditions, and personal protective equipment (PPE). Sadly, this is not happening for many essential workers, such as those working in home health care and in the meat processing industry. These workers are not only being unnecessarily exposed to the virus, but they are also not receiving paid sick leave, unemployment benefits, and affordable health care and childcare. The lack of these protections is due to structural discrimination and has disproportionately disadvantaged women of color and low-wage …

The Problem With Relying On Profit-Driven Models To Produce Pandemic Drugs, Ana Santos Rutschman

All Faculty Scholarship

The longstanding problems of relying on a market response to a pandemic are becoming readily apparent in the United States, which has quickly become the epicenter of the COVID-19 outbreak. The problems are particularly pronounced in pharmaceutical markets, where we are pinning our hopes for both cures and vaccines. In previous work we have shown how characteristics of healthcare markets in the United States create a divergence between the private incentives of for-profit companies and public health needs, leading to sub-optimal health outcomes in what is a uniquely market-driven healthcare system. In this Essay, written as the COVID-19 pandemic unfolds, …

The Reemergence Of Vaccine Nationalism, Ana Santos Rutschman

All Faculty Scholarship

This short essay explores the reemergence of vaccine nationalism during the COVID-19 pandemic. The essay traces the pre-COVID origins of vaccine nationalism and explains how it can have detrimental effects on equitable access to newly developed vaccines.

Substance Use Disorder, Discrimination, And The Cares Act: Using Disability Law To Strengthen New Protections, Kelly K. Dineen, Elizabeth Pendo

All Faculty Scholarship

The COVID-19 pandemic is having devastating consequences for people with substance use disorders (SUD). SUD is a chronic health condition—like people with other chronic health conditions, people with SUD experience periods of remission and periods of exacerbation and relapse. Unlike people with most other chronic conditions, people with SUD who experience a relapse may face criminal charges and incarceration. They are chronically disadvantaged by pervasive social stigma, discrimination, and structural inequities. People with SUD are also at higher risk for both contracting the SARS-CoV-19 virus and experiencing poorer outcomes. Meanwhile, there are early indications that pandemic conditions have led to …

Employee Testing, Tracing, And Disclosure As A Response To The Coronavirus Pandemic, Matthew T. Bodie, Michael Mcmahon

All Faculty Scholarship

As the COVID-19 pandemic continues to devastate the United States, the federal government has largely failed to implement a national program to prevent and contain the virus. As a result, many employers have undertaken their own workplace coronavirus mitigation efforts. This essay examines, in three parts, the legal framework surrounding employer systems of workplace testing, tracing, and disclosure. It first examines the legal issues surrounding employer-mandated COVID-19 testing and temperature checks, especially issues arising under the Americans with Disabilities Act (ADA) and Health Information Portability and Accountability Act (HIPAA). Regarding employer contact tracing efforts, the essay next reviews the multitude …

Comments On The Preliminary Framework For Equitable Allocation Of Covid-19 Vaccine, Ana Santos Rutschman, Julia Barnes-Weise, Robert Gatter, Timothy L. Wiemken

All Faculty Scholarship

On September 1, 2020 the National Academies released a draft framework for Equitable Allocation of a COVID-19 Vaccine. In this response, we analyze the proposed framework and highlight several areas.

Among the proposed changes, we highlight the need for the following interventions. The final framework for distribution of COVID-19 vaccines should give a higher priority to populations made most vulnerable by the social determinants of health. It should incorporate more geography-based approaches in at least some of the four proposed phases of vaccine distribution. It should address the possibility of a vaccine being made available through an emergency use authorization …

'Terroristic Threats' And Covid-19: A Guide For The Perplexed, Chad Flanders, Courtney Federico, Eric Harmon, Lucas Klein

All Faculty Scholarship

The first few months of the COVID-19 outbreak in the United States saw the rise of a troubling sort of behavior: people would cough or spit on people or otherwise threaten to spread the COVID-19 virus, resulting in panic and sometimes thousands of dollars’ worth of damages to businesses. Those who have been caught doing this — or have filmed themselves doing it — have been charged under so-called “terroristic threat” statutes. But what is a terroristic threat, and is it an appropriate charge in these cases? Surprisingly little has been written about these statutes given their long history and …

Biopsychosocial Risk Factors And Knowledge Of Cervical Cancer Among Young Women: A Case Study From Kenya To Inform Hpv Prevention In Sub-Saharan Africa, Irene Ngune, Fatch Kalembo, Barbara Loessl, Lucy W. Kivuti-Bitok

Research outputs 2014 to 2021

Background Cervical cancer is the second most common female reproductive cancer after breast cancer with 84% of the cases in developing countries. A high uptake of human papilloma virus (HPV) vaccination and screening, and early diagnosis leads to a reduction of incidence and mortality rates. Yet uptake of screening is low in Sub-Saharan Africa and there is an increasing number of women presenting for treatment with advanced disease. Nine women in their twenties die from cervical cancer in Kenya every day. This paper presents the biopsychosocial risk factors that impact on cervical cancer knowledge among Kenyan women aged 15 to …

Super Learner Analysis Of Real-Time Electronically Monitored Adherence To Antiretroviral Therapy Under Constrained Optimization And Comparison To Non-Differentiated Care Approaches For Persons Living With Hiv In Rural Uganda, Alejandra E. Benitez, Nicholas Musinguzi, David Bangsberg, Mwebesa B. Bwana, Conrad Muzoora, Peter Hunt, Jeffrey N. Martin, Jessica E. Haberer, Maya L. Petersen

OHSU-PSU School of Public Health Faculty Publications and Presentations

Introduction

Real‐time electronic adherence monitoring (EAM) systems could inform on‐going risk assessment for HIV viraemia and be used to personalize viral load testing schedules. We evaluated the potential of real‐time EAM (transferred via cellular signal) and standard EAM (downloaded via USB cable) in rural Uganda to inform individually differentiated viral load testing strategies by applying machine learning approaches.

Methods

We evaluated an observational cohort of persons living with HIV and treated with antiretroviral therapy (ART) who were monitored longitudinally with standard EAM from 2005 to 2011 and real‐time EAM from 2011 to 2015. Super learner, an ensemble machine learning method, …

Hiv Care Continuum Characteristics Among People With Opioid Use Disorder And Hiv In Vietnam: Baseline Results From The Bravo Study, Caroline King, Le Minh Giang, Gavin Bart, Lynn Elizabeth Kunkel, P. Todd Korthuis

OHSU-PSU School of Public Health Faculty Publications and Presentations

Background

Little is known about patient characteristics that contribute to initiating antiretroviral therapy (ART) and achieving viral suppression among HIV people with opioid use disorder in Vietnam. The primary objective of this analysis was to evaluate associations between participant characteristics and the critical steps in the HIV care continuum of ART initiation and HIV viral suppression among people with opioid use disorder and HIV in Vietnam.

Methods

We assessed baseline participant characteristics, ART status, and HIV viral suppression (HIV RNA PCR < 200 copies/mL) enrolled in a clinical trial of HIV clinic-based buprenorphine versus referral for methadone among people with opioid use disorder in Vietnam. We developed logistic regression models to identify characteristics associated with ART status and HIV viral suppression.

Results

Among 283 study participants, 191 (67.5%) were prescribed ART at baseline, and 168 of those on ART (90%) …

Analysis Of Covid-19 Transmission: Low Risk Of Presymptomatic Spread?, Mark K. Slifka, William B. Messer, Ian J. Amanna

OHSU-PSU School of Public Health Faculty Publications and Presentations

More than 6 million confirmed cases of COVID-19 (coronavirus disease 2019) have been identified worldwide and a number of case reports1-5 have indicated that COVID-19 has the potential to be transmitted prior to disease onset. Studies have also shown that infectious virus can be isolated from presymptomatic COVID-19 cases6 and although it is unknown what level of infectious virus is needed to confer efficient transmission potential, detection of infectious virus in the upper respiratory tract indicates that presymptomatic transmission of COVID-19 is plausible. Fear of asymptomatic and presymptomatic transmission of COVID-19 has led to considerable concern among public health policy …

Leveraging Technology To Blend Large-Scale Epidemiologic Surveillance With Social And Behavioral Science Methods: Successes, Challenges, And Lessons Learned Implementing The Unite Longitudinal Cohort Study Of Hiv Risk Factors Among Sexual Minority Men In The United States, H. Jonathon Rendina, Ali J. Talan, Nicola F. Tavella, Jonathan Lopez Matos, Ruben H. Jimenez, S. Scott Jones, Brian Salfas, Drew Westmoreland

Publications and Research

The use of digital technologies to conduct large-scale research with limited interaction (i.e., no in-person contact) and objective endpoints (i.e., biological testing) has significant potential for the field of epidemiology, but limited research to date has been published on the successes and challenges of such approaches. We analyzed data from a cohort study of sexual minority men across the United States, collected using digital strategies during a 10-month period from 2017 to 2018. Overall, 113,874 individuals were screened, of whom 26,000 were invited to the study, 10,691 joined the study, and 7,957 completed all enrollment steps, including return of a …

Prevalence And Correlates Of Transactional Sex Among Women Of Low Socioeconomic Status In Portland, Or, Timothy Menza, Lauren Lipira, Amisha Bhattarai, Victoria Cali-De Leon, E. Roberto Orellana

School of Social Work Faculty Publications and Presentations

Background: Women who report transactional sex are at increased risk for HIV and other sexually transmitted infections (STIs). However, in the United States, social, behavioral, and trauma-related vulnerabilities associated with transactional sex are understudied and data on access to biomedical HIV prevention among women who report transactional sex are limited.

Methods: In 2016, we conducted a population-based, cross-sectional survey of women of low socioeconomic status recruited via respondent-driven sampling in Portland, Oregon. We calculated the prevalence and, assessed the correlates of, transactional sex using generalized linear models accounting for sampling design. We also compared health outcomes, HIV screening, and knowledge …

Rapid Deployment Of A Statewide Covid-19 Echo Program For Frontline Clinicians: Early Results And Lessons Learned, Anna Louise Steeves-Reece, Nancy Elder, Tuesday A. Graham, Miriam L. Wolf, Isabel Stock, Melinda M. Davis, Robert D. Stock

OHSU-PSU School of Public Health Faculty Publications and Presentations

In a pattern repeated around the country, Oregon reported its first coronavirus patient on February 28, 2020.1 A week later, the governor declared a state of emergency.2 While the media initially focused on efforts to address COVID-19 in large cities, many rural communities were working in parallel to prepare. In these rural areas, there was an increasing concern that the burden of COVID-19 may be particularly dire due to factors such as older populations, higher prevalence of chronic diseases and poverty, and less health care access.3-6 Rural clinicians, especially those working in outpatient settings, are caring for patients during the …

Molecular Analysis Of Lymphoid Tissue From Rhesus Macaque Rhadinovirus-Infected Monkeys Identifies Alterations In Host Genes Associated With Oncogenesis, Ryan D. Estep, Aparna N. Govindan, Minsha Manoharan, He Li, Suzanne S. Fei, Byung S. Park, Michael K. Axthelm, Scott Wong

OHSU-PSU School of Public Health Faculty Publications and Presentations

Rhesus macaque (RM) rhadinovirus (RRV) is a simian gamma-2 herpesvirus closely related to human Kaposi’s sarcoma-associated herpesvirus (KSHV). RRV is associated with the development of diseases in simian immunodeficiency virus (SIV) co-infected RM that resemble KSHV-associated pathologies observed in HIV-infected humans, including B cell lymphoproliferative disorders (LPD) and lymphoma. Importantly, how de novo KSHV infection affects the expression of host genes in humans, and how these alterations in gene expression affect viral replication, latency, and disease is unknown. The utility of the RRV/RM infection model provides a novel approach to address these questions in vivo, and utilizing the RRV …

Role Of Ciliary Proteins Adp Ribosylation Factor Like Gtpase 13b (Arl13b) And Bardet-Biedl Syndrome-8 (Bbs8) In Photoreceptor Outer Segment Morphogenesis, Maintenance, And Viability, Tanya L. Dilan

Graduate Theses, Dissertations, and Problem Reports (ETD)

Photoreceptor neurons are modified primary cilia with an extended ciliary compartment known as the outer segment (OS). The mechanisms behind the elaboration of photoreceptor cilia, OS morphogenesis, and maintenance remain poorly understood. In this work, we focused on dissecting the role of two ciliary proteins, the small GTPase ADP-ribosylation factor-like GTPase 13B (ARL13B) and Bardet-Biedl Syndrome-8 (BBS8) in the context of photoreceptor biology. Both BBS8 and ARL13B are linked to defects in ciliogenesis (cilia development) and Retinitis Pigmentosa (vision loss). ARL13B is implicated in regulating ciliary length, and BBS8 is part of the Bardet-Biedl Syndrome complex (BBSome); the BBSome is …