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Effects Of Maternal Obesity And Gestational Diabetes Mellitus On The Placenta: Current Knowledge And Targets For Therapeutic Interventions, Samantha Bedell, Janine Hutson, Barbra De Vrijer, Genevieve Eastabrook Jan 2021

Effects Of Maternal Obesity And Gestational Diabetes Mellitus On The Placenta: Current Knowledge And Targets For Therapeutic Interventions, Samantha Bedell, Janine Hutson, Barbra De Vrijer, Genevieve Eastabrook

Obstetrics & Gynaecology Publications

Obesity and gestational diabetes mellitus (GDM) are becoming more common among pregnant women worldwide and are individually associated with a number of placenta-mediated obstetric complications, including preeclampsia, macrosomia, intrauterine growth restriction and stillbirth. The placenta serves several functions throughout pregnancy and is the main exchange site for the transfer of nutrients and gas from mother to fetus. In pregnancies complicated by maternal obesity or GDM, the placenta is exposed to environmental changes, such as increased inflammation and oxidative stress, dyslipidemia, and altered hormone levels. These changes can affect placental development and function and lead to abnormal fetal growth and development …


Physician Remuneration Schemes, Psychiatric Hospitalizations And Follow-Up Care: Evidence From Blended Fee-For-Service And Capitation Models., Thyna Vu, Kelly K Anderson, Rose Anne Devlin, Nibene H Somé, Sisira Sarma Jan 2021

Physician Remuneration Schemes, Psychiatric Hospitalizations And Follow-Up Care: Evidence From Blended Fee-For-Service And Capitation Models., Thyna Vu, Kelly K Anderson, Rose Anne Devlin, Nibene H Somé, Sisira Sarma

Epidemiology and Biostatistics Publications

Psychiatric hospitalizations could be reduced if mental illnesses were detected and treated earlier in the primary care setting, leading to the World Health Organization recommendation that mental health services be integrated into primary care. The mental health services provided in primary care settings may vary based on how physicians are incentivized. Little is known about the link between physician remuneration and psychiatric hospitalizations. We contribute to this literature by studying the relationship between physician remuneration and psychiatric hospitalizations in Canada's most populous province, Ontario. Specifically, we study family physicians (FPs) who switched from blended fee-for-service (FFS) to blended capitation remuneration …


Barriers And Facilitators To Implementation Of Oral Rehydration Therapy In Low- And Middle-Income Countries: A Systematic Review., Obidimma Ezezika, Apira Ragunathan, Yasmine El-Bakri, Kathryn Barrett Jan 2021

Barriers And Facilitators To Implementation Of Oral Rehydration Therapy In Low- And Middle-Income Countries: A Systematic Review., Obidimma Ezezika, Apira Ragunathan, Yasmine El-Bakri, Kathryn Barrett

Health Studies Publications

BACKGROUND: Oral rehydration therapy (ORT) is an effective and cheap treatment for diarrheal disease; globally, one of the leading causes of death in children under five. The World Health Organization launched a global campaign to improve ORT coverage in 1978, with activities such as educational campaigns, training health workers and the creation of designate programming. Despite these efforts, ORT coverage remains relatively low. The objective of this systematic review is to identify the barriers and facilitators to the implementation of oral rehydration therapy in low and middle-income countries.

METHODS: A comprehensive search strategy comprised of relevant subject headings and keywords …


The Effect Of Dual-Task Testing On Balance And Gait Performance In Adults With Type 1 Or Type 2 Diabetes Mellitus: A Systematic Review, Humberto Omana, Edward Madou, Manuel Montero-Odasso, Michael Payne, Ricardo Viana, Susan W. Hunter Jan 2021

The Effect Of Dual-Task Testing On Balance And Gait Performance In Adults With Type 1 Or Type 2 Diabetes Mellitus: A Systematic Review, Humberto Omana, Edward Madou, Manuel Montero-Odasso, Michael Payne, Ricardo Viana, Susan W. Hunter

Physical Therapy Publications

BACKGROUND: Individuals with diabetes mellitus (DM) are susceptible to balance, gait and cognitive impairments. Importantly, diabetes affects executive function, a set of cognitive processes critical to everyday cortical function and mobility. Reduced executive function is a risk factor for falls in people with DM. Dual-task testing, the completion of two tasks at once, enables the examination of the cognitive-mobility relationship. A synthesis of the literature on the effects of dual- task testing on the balance and gait of individuals with DM has not been performed.

OBJECTIVE: To systematically review the literature on the effect of dual-task testing on balance and …


Impact Of A Multidisciplinary Workflow On Safety And Management Of Patients With Heparin-Induced Thrombocytopenia, Sheh-Li Chen, Andrew P. Stivers, Jonathan D. Cicci, Tanner L. Hedrick, Marian A. Rollins-Raval, Raj S. Kasthuri, Kalynn A. Northam Jan 2021

Impact Of A Multidisciplinary Workflow On Safety And Management Of Patients With Heparin-Induced Thrombocytopenia, Sheh-Li Chen, Andrew P. Stivers, Jonathan D. Cicci, Tanner L. Hedrick, Marian A. Rollins-Raval, Raj S. Kasthuri, Kalynn A. Northam

Pathology Research and Scholarship

PURPOSE: Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin administration. Management strategies are complex and include discontinuing heparin products, initiating alternative anticoagulants, interpreting laboratory test results, documenting heparin allergies, and providing patient education. Medication error reports and a retrospective review conducted at an academic medical center revealed an opportunity for a quality improvement initiative and led to the creation of a multidisciplinary workflow for the management of HIT. In a pre-post study, the impact of the multidisciplinary workflow on the safety and management of HIT was evaluated.

METHODS: The preimplementation group consisted of adult patients tested for suspected HIT …


Regen Med Therapeutic Opportunities For Fighting Covid-19., Anthony Atala, Alicia Henn, Martha Lundberg, Taby Ahsan, Jordan Greenberg, Jeff Krukin, Steven Lynum, Cathleen Lutz, Kyle Cetrulo, Mohammad Albanna, Taciana Pereira, Shannon Eaker, Joshua Hunsberger Jan 2021

Regen Med Therapeutic Opportunities For Fighting Covid-19., Anthony Atala, Alicia Henn, Martha Lundberg, Taby Ahsan, Jordan Greenberg, Jeff Krukin, Steven Lynum, Cathleen Lutz, Kyle Cetrulo, Mohammad Albanna, Taciana Pereira, Shannon Eaker, Joshua Hunsberger

Faculty Research 2021

This perspective from a Regenerative Medicine Manufacturing Society working group highlights regenerative medicine therapeutic opportunities for fighting COVID-19. This article addresses why SARS-CoV-2 is so different from other viruses and how regenerative medicine is poised to deliver new therapeutic opportunities to battle COVID-19. We describe animal models that depict the mechanism of action for COVID-19 and that may help identify new treatments. Additionally, organoid platforms that can recapitulate some of the physiological properties of human organ systems, such as the lungs and the heart, are discussed as potential platforms that may prove useful in rapidly screening new drugs and identifying …


Genetic Variation In Genes Regulating Skeletal Muscle Regeneration And Tissue Remodelling Associated With Weight Loss In Chronic Obstructive Pulmonary Disease, Preeti Lakshman Kumar, Ava C. Wilson, Alison Rocco, Michael H. Cho, Emily Wan, Brian D. Hobbs, George R. Washko, Victor E. Ortega, Stephanie A. Christenson, Xingnan Li, J. Michael Wells, Surya P. Bhatt, Dawn L. Demeo, Sharon M. Lutz, Harry Rossiter, Richard Casaburi, Stephen I. Rennard, David A. Lomas, Wassim W. Labaki, Ruth Tal-Singer, Russel P. Bowler, Craig P. Hersh, Hemant K. Tiwari, Mark Dransfield, Anna Thalacker-Mercer, Deborah A. Meyers, Edwin K. Silverman, Merry-Lynn N. Mcdonald, Copdgene, Eclipse And Spiromics Investigators Jan 2021

Genetic Variation In Genes Regulating Skeletal Muscle Regeneration And Tissue Remodelling Associated With Weight Loss In Chronic Obstructive Pulmonary Disease, Preeti Lakshman Kumar, Ava C. Wilson, Alison Rocco, Michael H. Cho, Emily Wan, Brian D. Hobbs, George R. Washko, Victor E. Ortega, Stephanie A. Christenson, Xingnan Li, J. Michael Wells, Surya P. Bhatt, Dawn L. Demeo, Sharon M. Lutz, Harry Rossiter, Richard Casaburi, Stephen I. Rennard, David A. Lomas, Wassim W. Labaki, Ruth Tal-Singer, Russel P. Bowler, Craig P. Hersh, Hemant K. Tiwari, Mark Dransfield, Anna Thalacker-Mercer, Deborah A. Meyers, Edwin K. Silverman, Merry-Lynn N. Mcdonald, Copdgene, Eclipse And Spiromics Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. COPD patients with cachexia or weight loss have increased risk of death independent of body mass index (BMI) and lung function. We tested the hypothesis genetic variation is associated with weight loss in COPD using a genome-wide association study approach.

METHODS: Participants with COPD (N = 4308) from three studies (COPDGene, ECLIPSE, and SPIROMICS) were analysed. Discovery analyses were performed in COPDGene with replication in SPIROMICS and ECLIPSE. In COPDGene, weight loss was defined as self-reported unintentional weight loss > 5% in the past year or low …


The Effect Of Long-Acting Dual Bronchodilator Therapy On Exercise Tolerance, Dynamic Hyperinflation, And Dead Space During Constant Work Rate Exercise In Copd, William W. Stringer, Janos Porszasz, Min Cao, Harry B. Rossiter, Shahid Siddiqui, Stephen I. Rennard, Richard Casaburi Jan 2021

The Effect Of Long-Acting Dual Bronchodilator Therapy On Exercise Tolerance, Dynamic Hyperinflation, And Dead Space During Constant Work Rate Exercise In Copd, William W. Stringer, Janos Porszasz, Min Cao, Harry B. Rossiter, Shahid Siddiqui, Stephen I. Rennard, Richard Casaburi

Journal Articles: Pulmonary & Critical Care Med

We investigated whether dual bronchodilator therapy (glycopyrrolate/formoterol fumarate; GFF; Bevespi Aerosphere) would increase exercise tolerance during a high-intensity constant work rate exercise test (CWRET) and the relative contributions of dead space ventilation (VD/VT) and dynamic hyperinflation (change in inspiratory capacity) to exercise limitation in chronic obstructive pulmonary disease (COPD). In all, 48 patients with COPD (62.9 ± 7.6 yrs; 33 male; GOLD spirometry stage 1/2/3/4, n = 2/35/11/0) performed a randomized, double blind, placebo (PL) controlled, two-period crossover, single-center trial. Gas exchange and inspiratory capacity (IC) were assessed during cycle ergometry at 80% incremental exercise peak …


Longitudinal Imaging-Based Clusters In Former Smokers Of The Copd Cohort Associate With Clinical Characteristics: The Subpopulations And Intermediate Outcome Measures In Copd Study (Spiromics), Chunrui Zou, Frank Li, Jiwoong Choi, Babak Haghighi, Sanghun Choi, Prathish K. Rajaraman, Alejandro P. Comellas, John D. Newell, Chang Hyun Lee, R. Graham Barr, Eugene Bleecker, Christopher B. Cooper, David Couper, Meilan Han, Nadia N. Hansel, Richard E. Kanner, Ella A. Kazerooni, Eric C. Kleerup, Fernando J. Martinez, Wanda O'Neal, Robert Paine, Stephen I. Rennard, Benjamin M. Smith, Prescott G. Woodruff, Eric A. Hoffman, Ching-Long Lin Jan 2021

Longitudinal Imaging-Based Clusters In Former Smokers Of The Copd Cohort Associate With Clinical Characteristics: The Subpopulations And Intermediate Outcome Measures In Copd Study (Spiromics), Chunrui Zou, Frank Li, Jiwoong Choi, Babak Haghighi, Sanghun Choi, Prathish K. Rajaraman, Alejandro P. Comellas, John D. Newell, Chang Hyun Lee, R. Graham Barr, Eugene Bleecker, Christopher B. Cooper, David Couper, Meilan Han, Nadia N. Hansel, Richard E. Kanner, Ella A. Kazerooni, Eric C. Kleerup, Fernando J. Martinez, Wanda O'Neal, Robert Paine, Stephen I. Rennard, Benjamin M. Smith, Prescott G. Woodruff, Eric A. Hoffman, Ching-Long Lin

Journal Articles: Pulmonary & Critical Care Med

PURPOSE: Quantitative computed tomography (qCT) imaging-based cluster analysis identified clinically meaningful COPD former-smoker subgroups (clusters) based on cross-sectional data. We aimed to identify progression clusters for former smokers using longitudinal data.

PATIENTS AND METHODS: We selected 472 former smokers from SPIROMICS with a baseline visit and a one-year follow-up visit. A total of 150 qCT imaging-based variables, comprising 75 variables at baseline and their corresponding progression rates, were derived from the respective inspiration and expiration scans of the two visits. The COPD progression clusters identified were then associated with subject demography, clinical variables and biomarkers.

RESULTS: COPD severities at baseline …


Aldo-Keto Reductases And Cancer Drug Resistance, Trevor M. Penning, Sravan Jonnalagadda, Paul C. Trippier, Tea Lanišnik Rižner Jan 2021

Aldo-Keto Reductases And Cancer Drug Resistance, Trevor M. Penning, Sravan Jonnalagadda, Paul C. Trippier, Tea Lanišnik Rižner

Journal Articles: Pharmaceutical Sciences

Human aldo-keto reductases (AKRs) catalyze the NADPH-dependent reduction of carbonyl groups to alcohols for conjugation reactions to proceed. They are implicated in resistance to cancer chemotherapeutic agents either because they are directly involved in their metabolism or help eradicate the cellular stress created by these agents (e.g., reactive oxygen species and lipid peroxides). Furthermore, this cellular stress activates the Nuclear factor-erythroid 2 p45-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 pathway. As many human AKR genes are upregulated by the NRF2 transcription factor, this leads to a feed-forward mechanism to enhance drug resistance. Resistance to major classes of chemotherapeutic agents (anthracyclines, …


Child Health And The Implementation Of Community And District-Management Empowerment For Scale-Up (Codes) In Uganda: A Randomised Controlled Trial, Peter Waiswa, Flavia Mpanga, Danstan Bagenda, Rornald Muhumuza Kananura, Thomas O'Connell, Dorcus Kiwanuka Henriksson, Theresa Diaz, Florence Ayebare, Anne Ruhweza Katahoire, Eric Ssegujja, Anthony Mbonye, Stefan Swartling Peterson Jan 2021

Child Health And The Implementation Of Community And District-Management Empowerment For Scale-Up (Codes) In Uganda: A Randomised Controlled Trial, Peter Waiswa, Flavia Mpanga, Danstan Bagenda, Rornald Muhumuza Kananura, Thomas O'Connell, Dorcus Kiwanuka Henriksson, Theresa Diaz, Florence Ayebare, Anne Ruhweza Katahoire, Eric Ssegujja, Anthony Mbonye, Stefan Swartling Peterson

Journal Articles: Anesthesiology

INTRODUCTION: Uganda's district-level administrative units buttress the public healthcare system. In many districts, however, local capacity is incommensurate with that required to plan and implement quality health interventions. This study investigates how a district management strategy informed by local data and community dialogue influences health services.

METHODS: A 3-year randomised controlled trial (RCT) comprised of 16 Ugandan districts tested a management approach, Community and District-management Empowerment for Scale-up (CODES). Eight districts were randomly selected for each of the intervention and comparison areas. The approach relies on a customised set of data-driven diagnostic tools to identify and resolve health system bottlenecks. …


Identifying Sleep-Related Factors Associated With Cognitive Function In A Hispanics/Latinos Cohort: A Dual Random Forest Approach, Li Xiaojin, Cui Licong, Wang Fei, Paul E Schulz, Guo-Qiang Zhang Jan 2021

Identifying Sleep-Related Factors Associated With Cognitive Function In A Hispanics/Latinos Cohort: A Dual Random Forest Approach, Li Xiaojin, Cui Licong, Wang Fei, Paul E Schulz, Guo-Qiang Zhang

Faculty, Staff and Student Publications

Disordered sleep is associated with poor cognitive function and cognitive decline. However, little is known regarding the association of sleep-related factors with cognitive function in underrepresented cohorts such as the Hispanic/Latino population. Leveraging the National Sleep Research Resource, one of the most comprehensive collections of sleep studies, we identified a Hispanic/Latino cohort of 1,031 lower cognitive function cases and 2,062 normal controls. We developed a novel dual random forest (DRF) approach to discriminate cases against controls for estimating the potential impact of sleep-related variables related to the decline of cognitive function. Several important sleep-related factors were identified which may be …


Towards Digestible Digital Health Solutions: Application Of A Health Literacy Inclusive Development Framework For Peripartum Depression Management, Alexandra Zingg, Tavleen Singh, Sahiti Myneni Jan 2021

Towards Digestible Digital Health Solutions: Application Of A Health Literacy Inclusive Development Framework For Peripartum Depression Management, Alexandra Zingg, Tavleen Singh, Sahiti Myneni

Faculty, Staff and Student Publications

Women of low income and education have lower levels of peripartum depression (PPD) literacy, limiting their ability to recognize symptoms and make informed healthcare decisions. Existing digital solutions and underlying development frameworks for PPD lack an integrative approach addressing health literacy and related disparities. Therefore, we develop an integrative framework for digital content engineering in PPD self-management consisting of (a) user needs analysis, (b) inclusion of eHealth literacy principles (science and health literacy), and (c) mapping user needs to the Behavioral Intervention Technology model. Results revealed that perinatal women seeking mental health care prefer information in multisensory formats, and knowledge …


Cross-Vendor Ct Image Data Harmonization Using Cvh-Ct, Md Selim, Jie Zhang, Baowei Fei, Guo-Qiang Zhang, Gary Yeeming Ge, Jin Chen Jan 2021

Cross-Vendor Ct Image Data Harmonization Using Cvh-Ct, Md Selim, Jie Zhang, Baowei Fei, Guo-Qiang Zhang, Gary Yeeming Ge, Jin Chen

Faculty, Staff and Student Publications

While remarkable advances have been made in Computed Tomography (CT), most of the existing efforts focus on imaging enhancement while reducing radiation dose. How to harmonize CT image data captured using different scanners is vital in cross-center large-scale radiomics studies but remains the boundary to explore. Furthermore, the lack of paired training image problem makes it computationally challenging to adopt existing deep learning models. We propose a novel deep learning approach called CVH-CT for harmonizing CT images captured using scanners from different vendors. The generator of CVH-CT uses a self-attention mechanism to learn the scanner-related information. We also propose a …


Targeting Accuracy Considerations For Simultaneous Tumor Treating Fields Antimitotic Therapy During Robotic Hypofractionated Radiation Therapy., Sharmi Biswas, Irina Kapitanova, Sabrina Divekar, Jimm Grimm, Ian J Butterwick, Daniel Garren, Lawrence R Kleinberg, Kristin J Redmond, Michel Lacroix, Anand Mahadevan, Kenneth M Forster Jan 2021

Targeting Accuracy Considerations For Simultaneous Tumor Treating Fields Antimitotic Therapy During Robotic Hypofractionated Radiation Therapy., Sharmi Biswas, Irina Kapitanova, Sabrina Divekar, Jimm Grimm, Ian J Butterwick, Daniel Garren, Lawrence R Kleinberg, Kristin J Redmond, Michel Lacroix, Anand Mahadevan, Kenneth M Forster

College of Health Professions Faculty Papers

Purpose: Tumor treating fields (TTFields) is a novel antimitotic treatment that was first proven effective for glioblastoma multiforme, now with trials for several extracranial indications underway. Several studies focused on concurrent TTFields therapy with radiation in the same time period, but were not given simultaneously. This study evaluates the targeting accuracy of simultaneous radiation therapy while TTFields arrays are in place and powered on, ensuring that radiation does not interfere with TTFields and TTFields does not interfere with radiation. This is one of several options to enable TTFields to begin several weeks sooner, and opens potential for synergistic effects of …


Performance Of Deep Learning Synthetic Cts For Mr-Only Brain Radiation Therapy, Xiaoning Liu, Hajar Emami, Siamak P. Nejad-Davarani, Eric Morris, Lonni Schultz, Ming Dong, Carri K. Glide-Hurst Jan 2021

Performance Of Deep Learning Synthetic Cts For Mr-Only Brain Radiation Therapy, Xiaoning Liu, Hajar Emami, Siamak P. Nejad-Davarani, Eric Morris, Lonni Schultz, Ming Dong, Carri K. Glide-Hurst

Public Health Sciences Articles

PURPOSE: To evaluate the dosimetric and image-guided radiation therapy (IGRT) performance of a novel generative adversarial network (GAN) generated synthetic CT (synCT) in the brain and compare its performance for clinical use including conventional brain radiotherapy, cranial stereotactic radiosurgery (SRS), planar, and volumetric IGRT.

METHODS AND MATERIALS: SynCT images for 12 brain cancer patients (6 SRS, 6 conventional) were generated from T1-weighted postgadolinium magnetic resonance (MR) images by applying a GAN model with a residual network (ResNet) generator and a convolutional neural network (CNN) with 5 convolutional layers as the discriminator that classified input images as real or synthetic. Following …


Performance Of An Affordable Urine Self-Sampling Method For Human Papillomavirus Detection In Mexican Women, Rubí Hernández-López, Luis Hermosillo, Leith León-Maldonado, Rafael Velázquez-Cruz, Leticia Torres-Ibarra, Eduardo Lazcano-Ponce, Attila Lörincz, Cosette M. Wheeler, F Xavier Bosch, Jack Cuzick, Berenice Rivera-Paredez, Belinda Nedjai, Jorge Salmerón Jan 2021

Performance Of An Affordable Urine Self-Sampling Method For Human Papillomavirus Detection In Mexican Women, Rubí Hernández-López, Luis Hermosillo, Leith León-Maldonado, Rafael Velázquez-Cruz, Leticia Torres-Ibarra, Eduardo Lazcano-Ponce, Attila Lörincz, Cosette M. Wheeler, F Xavier Bosch, Jack Cuzick, Berenice Rivera-Paredez, Belinda Nedjai, Jorge Salmerón

Pathology Research and Scholarship

INTRODUCTION: Urine self-sampling for human papillomavirus (HPV)-based cervical cancer screening is a non-invasive method that offers several logistical advantages and high acceptability, reducing barriers related to low screening coverage. This study developed and evaluated the performance of a low-cost urine self-sampling method for HPV-testing and explored the acceptability and feasibility of potential implementation of this alternative in routine screening.

METHODS: A series of sequential laboratory assays examined the impact of several pre-analytical conditions for obtaining DNA from urine and subsequent HPV detection. Initially, we assessed the effect of ethylaminediaminetetraacetic acid (EDTA) as a DNA preservative examining several variables including EDTA …


Lying In Wait: The Resurgence Of Dengue Virus After The Zika Epidemic In Brazil, Anderson Fernandes Brito, Lais Ceschini Machado, Rachel J. Oidtman, Márcio Junio Lima Siconelli, Quan Minh Tran, Joseph R. Fauver, Rodrigo Dias De Oliveira Carvalho, Filipe Zimmer Dezordi, Mylena Ribeiro Pereira, Luiza Antunes De Castro-Jorge, Elaine Cristina Manini Minto, Luzia Márcia Romanholi Passos, Chaney C. Kalinich, Mary E. Petrone, Emma Allen, Guido Camargo España, Angkana T. Huang, Derek A. T. Cummings, Guy Baele, Rafael Freitas Oliveira Franca, Benedito Antônio Lopes Da Fonseca, T. Alex Perkins, Gabriel Luz Wallau, Nathan D. Grubaugh Jan 2021

Lying In Wait: The Resurgence Of Dengue Virus After The Zika Epidemic In Brazil, Anderson Fernandes Brito, Lais Ceschini Machado, Rachel J. Oidtman, Márcio Junio Lima Siconelli, Quan Minh Tran, Joseph R. Fauver, Rodrigo Dias De Oliveira Carvalho, Filipe Zimmer Dezordi, Mylena Ribeiro Pereira, Luiza Antunes De Castro-Jorge, Elaine Cristina Manini Minto, Luzia Márcia Romanholi Passos, Chaney C. Kalinich, Mary E. Petrone, Emma Allen, Guido Camargo España, Angkana T. Huang, Derek A. T. Cummings, Guy Baele, Rafael Freitas Oliveira Franca, Benedito Antônio Lopes Da Fonseca, T. Alex Perkins, Gabriel Luz Wallau, Nathan D. Grubaugh

Journal Articles: Epidemiology

After the Zika virus (ZIKV) epidemic in the Americas in 2016, both Zika and dengue incidence declined to record lows in many countries in 2017-2018, but in 2019 dengue resurged in Brazil, causing ~2.1 million cases. In this study we use epidemiological, climatological and genomic data to investigate dengue dynamics in recent years in Brazil. First, we estimate dengue virus force of infection (FOI) and model mosquito-borne transmission suitability since the early 2000s. Our estimates reveal that DENV transmission was low in 2017-2018, despite conditions being suitable for viral spread. Our study also shows a marked decline in dengue susceptibility …


Viral Dynamics Of Acute Sars-Cov-2 Infection And Applications To Diagnostic And Public Health Strategies, Stephen M. Kissler, Joseph R. Fauver, Christina Mack, Scott W. Olesen, Caroline Tai, Kristin Y. Shiue, Chaney C. Kalinich, Sarah Jednak, Isabel M. Ott, Chantal B. F. Vogels, Jay Wohlgemuth, James Weisberger, John Difiori, Deverick J. Anderson, Jimmie Mancell, David D. Ho, Nathan D. Grubaugh, Yonatan H. Grad Jan 2021

Viral Dynamics Of Acute Sars-Cov-2 Infection And Applications To Diagnostic And Public Health Strategies, Stephen M. Kissler, Joseph R. Fauver, Christina Mack, Scott W. Olesen, Caroline Tai, Kristin Y. Shiue, Chaney C. Kalinich, Sarah Jednak, Isabel M. Ott, Chantal B. F. Vogels, Jay Wohlgemuth, James Weisberger, John Difiori, Deverick J. Anderson, Jimmie Mancell, David D. Ho, Nathan D. Grubaugh, Yonatan H. Grad

Journal Articles: Epidemiology

SARS-CoV-2 infections are characterized by viral proliferation and clearance phases and can be followed by low-level persistent viral RNA shedding. The dynamics of viral RNA concentration, particularly in the early stages of infection, can inform clinical measures and interventions such as test-based screening. We used prospective longitudinal quantitative reverse transcription PCR testing to measure the viral RNA trajectories for 68 individuals during the resumption of the 2019-2020 National Basketball Association season. For 46 individuals with acute infections, we inferred the peak viral concentration and the duration of the viral proliferation and clearance phases. According to our mathematical model, we found …


Taking Account Of Asymptomatic Infections: A Modeling Study Of The Covid-19 Outbreak On The Diamond Princess Cruise Ship, Li-Shan Huang, Li Li, Lucia Dunn, Mai He Jan 2021

Taking Account Of Asymptomatic Infections: A Modeling Study Of The Covid-19 Outbreak On The Diamond Princess Cruise Ship, Li-Shan Huang, Li Li, Lucia Dunn, Mai He

Open Access Publications

The COVID-19 outbreak on the Diamond Princess (DP) cruise ship has provided empirical data to study the transmission potential of COVID-19 with the presence of pre/asymptomatic cases. We studied the changes in R0 on DP from January 21 to February 19, 2020 based on chain binomial models under two scenarios: no quarantine assuming a random mixing condition, and quarantine of passengers in cabins-passengers may get infected either by an infectious case in a shared cabin or by pre/asymptomatic crew who continued to work. Estimates of R0 at the beginning of the epidemic were 3.27 (95% CI, 3.02-3.54) and 3.78 (95% …


Guidelines For Conducting Virtual Cognitive Interviews During A Pandemic, James A Shepperd, Gabrielle Pogge, Jean M Hunleth, Sienna Ruiz, Erika A Waters Jan 2021

Guidelines For Conducting Virtual Cognitive Interviews During A Pandemic, James A Shepperd, Gabrielle Pogge, Jean M Hunleth, Sienna Ruiz, Erika A Waters

Open Access Publications

The COVID-19 pandemic has challenged researchers working in physical contact with research participants. Cognitive interviews examine whether study components (most often questionnaire items) are worded or structured in a manner that allows study participants to interpret the items in a way intended by the researcher. We developed guidelines to conduct cognitive interviews virtually to accommodate interviewees who have limited access to the internet. The guidelines describe the essential communication and safety equipment requirements and outline a procedure for collecting responses while maintaining the safety of the participants and researchers. Furthermore, the guidelines provide suggestions regarding training of participants to use …


Cxcl17 Is A Specific Diagnostic Biomarker For Severe Pandemic Influenza A(H1n1) That Predicts Poor Clinical Outcome, Jose Alberto Choreño-Parra, Shabaana A Khader, Et Al Jan 2021

Cxcl17 Is A Specific Diagnostic Biomarker For Severe Pandemic Influenza A(H1n1) That Predicts Poor Clinical Outcome, Jose Alberto Choreño-Parra, Shabaana A Khader, Et Al

Open Access Publications

The C-X-C motif chemokine ligand 17 (CXCL17) is chemotactic for myeloid cells, exhibits bactericidal activity, and exerts anti-viral functions. This chemokine is constitutively expressed in the respiratory tract, suggesting a role in lung defenses. However, little is known about the participation of CXCL17 against relevant respiratory pathogens in humans. Here, we evaluated the serum levels and lung tissue expression pattern of CXCL17 in a cohort of patients with severe pandemic influenza A(H1N1) from Mexico City. Peripheral blood samples obtained on admission and seven days after hospitalization were processed for determinations of serum CXCL17 levels by enzyme-linked immunosorbent assay (ELISA). The …


Association Of Circulating Sex Hormones With Inflammation And Disease Severity In Patients With Covid-19, Sandeep Dhindsa, Nan Zhang, Michael J. Mcphaul, Zengru Wu, Amit K. Ghoshal, Emma C. Erlich, Kartik Mani, Gwendalyn J. Randolph, John R. Edwards, Philip A. Mudd, Abhinav Diwan Jan 2021

Association Of Circulating Sex Hormones With Inflammation And Disease Severity In Patients With Covid-19, Sandeep Dhindsa, Nan Zhang, Michael J. Mcphaul, Zengru Wu, Amit K. Ghoshal, Emma C. Erlich, Kartik Mani, Gwendalyn J. Randolph, John R. Edwards, Philip A. Mudd, Abhinav Diwan

Open Access Publications

Importance: Male sex is a risk factor for developing severe COVID-19 illness. It is not known whether sex hormones contribute to this predisposition.

Objective: To investigate the association of concentrations of serum testosterone, estradiol, and insulinlike growth factor 1 (IGF-1, concentrations of which are regulated by sex hormone signaling) with COVID-19 severity.

Design, Setting, and Participants: This prospective cohort study was conducted using serum samples collected from consecutive patients who presented from March through May 2020 to the Barnes Jewish Hospital in St Louis, Missouri, with COVID-19 (diagnosed using nasopharyngeal swabs).

Exposures: Testosterone, estradiol, and IGF-1 concentrations were measured at …


Characteristics And Outcomes Among Us Patients Hospitalized For Ischemic Stroke Before Vs During The Covid-19 Pandemic, Adam De Havenon, John P. Ney, Brian Callaghan, Samuel Hohmann, Ernie Shippey, Shadi Yaghi, Mohammad Anadani, Jennifer J. Majersik Jan 2021

Characteristics And Outcomes Among Us Patients Hospitalized For Ischemic Stroke Before Vs During The Covid-19 Pandemic, Adam De Havenon, John P. Ney, Brian Callaghan, Samuel Hohmann, Ernie Shippey, Shadi Yaghi, Mohammad Anadani, Jennifer J. Majersik

Open Access Publications

Importance: After the emergence of COVID-19, studies reported a decrease in hospitalizations of patients with ischemic stroke (IS), but there are little to no data regarding hospitalizations for the remainder of 2020, including outcome data from a large cohort of patients with IS and comorbid COVID-19.

Objective: To assess hospital discharge rates, demographic factors, and outcomes of hospitalization associated with the COVID-19 pandemic among US patients with IS before vs during the COVID-19 pandemic.

Design, Setting, and Participants: This retrospective cohort study used data from the Vizient Clinical Data Base on 324 013 patients with IS at 478 nonfederal hospitals …


Response To Ibudilast Treatment According To Progressive Multiple Sclerosis Disease Phenotype, Andrew D Goodman, Janel K Fedler, Jon Yankey, Elizabeth A Klingner, Dixie J Ecklund, Christopher V Goebel, Robert A Bermel, Marianne Chase, Christopher S Coffey, Eric C Klawiter, Robert T Naismith, Robert J Fox, Sprint-Ms Investigators Jan 2021

Response To Ibudilast Treatment According To Progressive Multiple Sclerosis Disease Phenotype, Andrew D Goodman, Janel K Fedler, Jon Yankey, Elizabeth A Klingner, Dixie J Ecklund, Christopher V Goebel, Robert A Bermel, Marianne Chase, Christopher S Coffey, Eric C Klawiter, Robert T Naismith, Robert J Fox, Sprint-Ms Investigators

Open Access Publications

OBJECTIVE: Determine whether a treatment effect of ibudilast on brain atrophy rate differs between participants with primary (PPMS) and secondary (SPMS) progressive multiple sclerosis.

BACKGROUND: Progressive forms of MS are both associated with continuous disability progression. Whether PPMS and SPMS differ in treatment response remains unknown.

DESIGN/METHODS: SPRINT-MS was a randomized, placebo-controlled 96-week phase 2 trial in both PPMS (n = 134) and SPMS (n = 121) patients. The effect of PPMS and SPMS phenotype on the rate of change of brain atrophy measured by brain parenchymal fraction (BPF) was examined by fitting a three-way interaction linear-mixed model. Adjustment for …


Rna-Seq Identifies Genes Whose Proteins Are Upregulated During Syncytia Development In Murine C2c12 Myoblasts And Human Bewo Trophoblasts, Christopher Azar, Mark C Valentine, Julie Trausch-Azar, Lisa Rois, Moe Mahjoub, D Michael Nelson, Alan L Schwartz Jan 2021

Rna-Seq Identifies Genes Whose Proteins Are Upregulated During Syncytia Development In Murine C2c12 Myoblasts And Human Bewo Trophoblasts, Christopher Azar, Mark C Valentine, Julie Trausch-Azar, Lisa Rois, Moe Mahjoub, D Michael Nelson, Alan L Schwartz

Open Access Publications

The fusion of villous cytotrophoblasts into the multinucleated syncytiotrophoblast is critical for the essential functions of the mammalian placenta. Using RNA-Seq gene expression, quantitative protein expression, and siRNA knockdown we identified genes and their cognate proteins which are similarly upregulated in two cellular models of mammalian syncytia development (human BeWo cytotrophoblast to syncytiotrophoblast and murine C2C12 myoblast to myotube). These include DYSF, PDE4DIP, SPIRE2, NDRG1, PLEC, GPR146, HSPB8, DHCR7, and HDAC5. These findings provide avenues for further understanding of the mechanisms underlying mammalian placental syncytiotrophoblast development.


Lack Of Association Between Acute Stroke, Post-Stroke Dementia, Race, And Β-Amyloid Status, Lauren N Koenig, Lena M Mccue, Elizabeth Grant, Parinaz Massoumzadeh, Catherine M Roe, Chengjie Xiong, Krista L Moulder, Liang Wang, Allyson R Zazulia, Peggy Kelly, Aylin Dincer, Aiad Zaza, Joshua S Shimony, Tammie L S Benzinger, John C Morris Jan 2021

Lack Of Association Between Acute Stroke, Post-Stroke Dementia, Race, And Β-Amyloid Status, Lauren N Koenig, Lena M Mccue, Elizabeth Grant, Parinaz Massoumzadeh, Catherine M Roe, Chengjie Xiong, Krista L Moulder, Liang Wang, Allyson R Zazulia, Peggy Kelly, Aylin Dincer, Aiad Zaza, Joshua S Shimony, Tammie L S Benzinger, John C Morris

Open Access Publications

INTRODUCTION: Stroke and Alzheimer disease share risk factors and often co-occur, and both have been reported to have a higher prevalence in African Americans as compared to non-Hispanic whites. However, their interaction has not been established. The objective of this study was to determine if preclinical Alzheimer disease is a risk factor for stroke and post-stroke dementia and whether racial differences moderate this relationship.

METHODS: This case-control study was analyzed in 2019 using retrospective data from 2007 to 2013. Participants were adults age 65 and older with and without acute ischemic stroke. Recruitment included word of mouth and referrals in …


Immunological Findings And Clinical Outcomes Of Infants With Positive Newborn Screening For Severe Combined Immunodeficiency From A Tertiary Care Center In The U.S., Vasudha Mantravadi, Jeffrey J Bednarski, Michelle A Ritter, Hongjie Gu, Ana L Kolicheski, Caroline Horner, Megan A Cooper, Maleewan Kitcharoensakkul Jan 2021

Immunological Findings And Clinical Outcomes Of Infants With Positive Newborn Screening For Severe Combined Immunodeficiency From A Tertiary Care Center In The U.S., Vasudha Mantravadi, Jeffrey J Bednarski, Michelle A Ritter, Hongjie Gu, Ana L Kolicheski, Caroline Horner, Megan A Cooper, Maleewan Kitcharoensakkul

Open Access Publications

The implementation of severe combined immunodeficiency (SCID) newborn screening has played a pivotal role in identifying these patients early in life as well as detecting various milder forms of T cell lymphopenia (TCL). In this study we reviewed the diagnostic and clinical outcomes, and interesting immunology findings of term infants referred to a tertiary care center with abnormal newborn SCID screens over a 6-year period. Key findings included a 33% incidence of non-SCID TCL including infants with novel variants in


Antigen Presenting Cells Link The Female Genital Tract Microbiome To Mucosal Inflammation, With Hormonal Contraception As An Additional Modulator Of Inflammatory Signatures, Elizabeth H Byrne, Barry L Hykes, Scott A Handley, Et Al Jan 2021

Antigen Presenting Cells Link The Female Genital Tract Microbiome To Mucosal Inflammation, With Hormonal Contraception As An Additional Modulator Of Inflammatory Signatures, Elizabeth H Byrne, Barry L Hykes, Scott A Handley, Et Al

Open Access Publications

The microbiome of the female genital tract (FGT) is closely linked to reproductive health outcomes. Diverse, anaerobe-dominated communities with low


Mr Elastography Demonstrates Reduced White Matter Shear Stiffness In Early-Onset Hydrocephalus, M E Wagshul, J P Mcallister, D D Limbrick Jr, S Yang, W Mowrey, J T Goodrich, A Meiri, D M Morales, A Kobets, R Abbott Jan 2021

Mr Elastography Demonstrates Reduced White Matter Shear Stiffness In Early-Onset Hydrocephalus, M E Wagshul, J P Mcallister, D D Limbrick Jr, S Yang, W Mowrey, J T Goodrich, A Meiri, D M Morales, A Kobets, R Abbott

Open Access Publications

INTRODUCTION: Hydrocephalus that develops early in life is often accompanied by developmental delays, headaches and other neurological deficits, which may be associated with changes in brain shear stiffness. However, noninvasive approaches to measuring stiffness are limited. Magnetic Resonance Elastography (MRE) of the brain is a relatively new noninvasive imaging method that provides quantitative measures of brain tissue stiffness. Herein, we aimed to use MRE to assess brain stiffness in hydrocephalus patients compared to healthy controls, and to assess its associations with ventricular size, as well as demographic, shunt-related and clinical outcome measures.

METHODS: MRE was collected at two imaging sites …