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Rugged Landscapes: Complexity And Implementation Science, Joseph T Ornstein, Ross A Hammond, Margaret Padek, Stephanie Mazzucca, Ross C Brownson Sep 2020

Rugged Landscapes: Complexity And Implementation Science, Joseph T Ornstein, Ross A Hammond, Margaret Padek, Stephanie Mazzucca, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: Mis-implementation-defined as failure to successfully implement and continue evidence-based programs-is widespread in public health practice. Yet the causes of this phenomenon are poorly understood.

METHODS: We develop an agent-based computational model to explore how complexity hinders effective implementation. The model is adapted from the evolutionary biology literature and incorporates three distinct complexities faced in public health practice: dimensionality, ruggedness, and context-specificity. Agents in the model attempt to solve problems using one of three approaches-Plan-Do-Study-Act (PDSA), evidence-based interventions (EBIs), and evidence-based decision-making (EBDM).

RESULTS: The model demonstrates that the most effective approach to implementation and quality improvement depends on the …


Phenotypic Diversity In An International Cure Vcp Disease Registry, Chiseko Ikenaga, Andrew R Findlay, Michelle Seiffert, Allison Peck, Nathan Peck, Nicholas E Johnson, Jeffrey M Statland, Conrad C Weihl Sep 2020

Phenotypic Diversity In An International Cure Vcp Disease Registry, Chiseko Ikenaga, Andrew R Findlay, Michelle Seiffert, Allison Peck, Nathan Peck, Nicholas E Johnson, Jeffrey M Statland, Conrad C Weihl

2020-Current year OA Pubs

BACKGROUND: Dominant mutations in valosin-containing protein (VCP) gene cause an adult onset inclusion body myopathy, Paget's disease of bone, and frontotemporal dementia also termed multisystem proteinopathy (MSP). The genotype-phenotype relationships in VCP-related MSP are still being defined; in order to understand this better, we investigated the phenotypic diversity and patterns of weakness in the Cure VCP Disease Patient Registry.

METHODS: Cure VCP Disease, Inc. was founded in 2018 for the purpose of connecting patients with VCP gene mutations and researchers to help advance treatments and cures. Cure VCP Disease Patient Registry is maintained by Coordination of Rare Diseases at Sanford. …


Raman-Guided Subcellular Pharmaco-Metabolomics For Metastatic Melanoma Cells., Jiajun Du, Yapeng Su, Chenxi Qian, Dan Yuan, Kun Miao, Dongkwan Lee, Alphonsus H C Ng, Reto S Wijker, Antoni Ribas, Raphael D Levine, James R Heath, Lu Wei Sep 2020

Raman-Guided Subcellular Pharmaco-Metabolomics For Metastatic Melanoma Cells., Jiajun Du, Yapeng Su, Chenxi Qian, Dan Yuan, Kun Miao, Dongkwan Lee, Alphonsus H C Ng, Reto S Wijker, Antoni Ribas, Raphael D Levine, James R Heath, Lu Wei

Articles, Abstracts, and Reports

Non-invasively probing metabolites within single live cells is highly desired but challenging. Here we utilize Raman spectro-microscopy for spatial mapping of metabolites within single cells, with the specific goal of identifying druggable metabolic susceptibilities from a series of patient-derived melanoma cell lines. Each cell line represents a different characteristic level of cancer cell de-differentiation. First, with Raman spectroscopy, followed by stimulated Raman scattering (SRS) microscopy and transcriptomics analysis, we identify the fatty acid synthesis pathway as a druggable susceptibility for differentiated melanocytic cells. We then utilize hyperspectral-SRS imaging of intracellular lipid droplets to identify a previously unknown susceptibility of lipid …


Preparing For Medical Internship: A Case-Based Strategy To Teach Management Of Common Overnight Calls To Students, Erica Lescinskas, Zaven Sargsyan, Uma S Ayyala, Joslyn Fisher Sep 2020

Preparing For Medical Internship: A Case-Based Strategy To Teach Management Of Common Overnight Calls To Students, Erica Lescinskas, Zaven Sargsyan, Uma S Ayyala, Joslyn Fisher

Faculty, Staff and Students Publications

INTRODUCTION: More medical schools are offering a transition-to-intern-year course to better prepare graduates for residency. Sessions where students simulate receiving cross-cover calls are frequently included and highly rated. However, simulated sessions are often resource intensive and therefore challenging to implement in all schools. We developed a case-based exercise to address this need.

METHODS: In 2009, our school implemented a required course focused on the transition-to-intern year, including a common overnight calls (COC) module. Students rotated through different stations in small groups which were each led by a facilitator. Topics have evolved in response to feedback, and current topics included altered …


A Novel Bioaugmentation Technique Effectively Increases The Skin-Associated Microbial Diversity Of Captive Eastern Hellbenders, Erin K. Kenison, Obed Hernandez-Gomez, Rod N. Williams Sep 2020

A Novel Bioaugmentation Technique Effectively Increases The Skin-Associated Microbial Diversity Of Captive Eastern Hellbenders, Erin K. Kenison, Obed Hernandez-Gomez, Rod N. Williams

Natural Sciences and Mathematics | Faculty Scholarship

Captive environments are maintained in hygienic ways that lack free-flowing microbes found in animals’ natural environments. As a result, captive animals often have depauperate host-associated microbial communities compared to conspecifics in the wild and may have increased disease susceptibility and reduced immune function. Eastern hellbenders (Cryptobranchus alleganiensis alleganiensis) have suffered precipitous population declines over the past few decades. To bolster populations, eastern hellbenders are reared in captivity before being translocated to the wild. However, the absence of natural microbial reservoirs within the captive environment diminishes the diversity of skin-associated bacteria on hellbender skin and may negatively influence their ability to …


Applying The Who Icf Framework To The Outcome Measures Used In The Evaluation Of Long-Term Clinical Outcomes In Coronavirus Outbreaks, Kajal Patel, Sofia Straudi, Ng Yee Sien, Nora Fayed, John L. Melvin, Manoj Sivan Sep 2020

Applying The Who Icf Framework To The Outcome Measures Used In The Evaluation Of Long-Term Clinical Outcomes In Coronavirus Outbreaks, Kajal Patel, Sofia Straudi, Ng Yee Sien, Nora Fayed, John L. Melvin, Manoj Sivan

Department of Rehabilitation Medicine Faculty Papers

(1) Objective: The World Health Organization's (WHO) International Classification of Functioning, Disability and Health (ICF) classification is a unified framework for the description of health and health-related states. This study aimed to use the ICF framework to classify outcome measures used in follow-up studies of coronavirus outbreaks and make recommendations for future studies. (2) Methods: EMBASE, MEDLINE, CINAHL and PsycINFO were systematically searched for original studies assessing clinical outcomes in adult survivors of severe acute respiratory distress syndrome (SARS), middle east respiratory syndrome (MERS) and coronavirus disease-19 (COVID-19) after hospital discharge. Individual items of the identified outcome measures were linked …


Population-Level Covid-19 Mortality Risk For Non-Elderly Individuals Overall And For Non-Elderly Individuals Without Underlying Diseases In Pandemic Epicenters, John P.A. Ioannidis, Cathrine Axfors, Despina G. Contopoulos-Ioannidis Sep 2020

Population-Level Covid-19 Mortality Risk For Non-Elderly Individuals Overall And For Non-Elderly Individuals Without Underlying Diseases In Pandemic Epicenters, John P.A. Ioannidis, Cathrine Axfors, Despina G. Contopoulos-Ioannidis

All publications

Objective: To provide estimates of the relative rate of COVID-19 death in people < 65 years old versus older individuals in the general population, the absolute risk of COVID-19 death at the population level during the first epidemic wave, and the proportion of COVID-19 deaths in non-elderly people without underlying diseases in epicenters of the pandemic.

Eligible data: Cross-sectional survey of countries and US states with at least 800 COVID-19 deaths as of April 24, 2020 and with information on the number of deaths in people with age < 65. Data were available for 14 countries (Belgium, Canada, France, Germany, India, Ireland, Italy, Mexico, Netherlands, Portugal, Spain, Sweden, Switzerland, UK) and 13 US states (California, Connecticut, Florida, Georgia, Illinois, Indiana, Louisiana, Maryland, Massachusetts, Michigan, New Jersey, New York, Pennsylvania). We also examined available data on COVID-19 deaths in people with age

Main outcome measures: Proportion of COVID-19 deaths in people < 65 years old; relative mortality rate of COVID-19 death in people < 65 versus ≥ 65 years old; absolute risk of COVID-19 death in people < 65 and in those ≥ 80 years old in the general population as of June 17, 2020; absolute COVID-19 mortality rate expressed as equivalent of mortality rate from driving a motor vehicle.

Results: Individuals with age < 65 account for 4.5–11.2% of all COVID-19 deaths in European countries and Canada, 8.3–22.7% in the US locations, and were the majority in India and Mexico. People < 65 years old had 30- to 100-fold lower risk of COVID-19 death than those ≥ 65 years old in 11 European countries and Canada, 16- to 52-fold lower risk in US locations, and less than 10-fold in India and Mexico. The absolute risk of COVID-19 death as of June 17, 2020 for people < 65 years old in high-income countries ranged from 10 (Germany) to 349 per million (New Jersey) and it was 5 per million in India and 96 per million in Mexico. The absolute risk of COVID-19 death for people ≥ 80 years old ranged from 0.6 (Florida) to 17.5 per thousand (Connecticut). The COVID-19 mortality rate in people < 65 years old during the period of fatalities from the epidemic was equivalent to the mortality rate from driving between 4 and 82 miles per day for 13 countries and 5 states, and was higher (equivalent to the mortality rate from driving 106–483 miles per day) for 8 other states and the UK. People < 65 years old without underlying predisposing conditions accounted for only 0.7–3.6% of all COVID-19 deaths in France, Italy, Netherlands, Sweden, Georgia, and New York City and 17.7% in Mexico.

Conclusions: People < 65 years old have very small risks of COVID-19 death even in pandemic epicenters and deaths for people < 65 years without underlying predisposing conditions are remarkably uncommon. Strategies focusing specifically on protecting high-risk elderly individuals should be considered in managing the pandemic.


Guidance For Contemporary Use Of Biologics In Management Of Chronic Rhinosinusitis With Nasal Polyps: Discussion From A National Institutes Of Health-Sponsored Workshop, Lauren T Roland, Timothy L Smith, Rodney J Schlosser, Zachary M Soler, Anju T Peters, Tanya M Laidlaw, Benjamin S Bleier, Vijay Ramakrishnan, Elina Toskala, David W Kennedy, Amber U Luong Sep 2020

Guidance For Contemporary Use Of Biologics In Management Of Chronic Rhinosinusitis With Nasal Polyps: Discussion From A National Institutes Of Health-Sponsored Workshop, Lauren T Roland, Timothy L Smith, Rodney J Schlosser, Zachary M Soler, Anju T Peters, Tanya M Laidlaw, Benjamin S Bleier, Vijay Ramakrishnan, Elina Toskala, David W Kennedy, Amber U Luong

Faculty, Staff and Student Publications

BACKGROUND: Biologic medications are emerging as options for treating chronic rhinosinusitis with nasal polyps (CRSwNP). Several questions remain regarding patient selection, indications, clinical efficacy, and cost effectiveness.

METHODS: In November 2019, a group of physicians and scientists gathered to consider strategies for future studies regarding biologics. During the discussion, gaps in knowledge highlighted a need for a consensus on the present day use of biologics in polyp patients.

RESULTS: The goal of this guideline is to propose recommendations for the current use of biologics in CRSwNP as new evidence continues to emerge and inform practice.

CONCLUSION: We suggest that physicians …


The Effect Of Exposure To Long Working Hours On Stroke: A Systematic Review And Meta-Analysis From The Who/Ilo Joint Estimates Of The Work-Related Burden Of Disease And Injury, Alexis Descatha, Bradley A Evanoff, Et Al Sep 2020

The Effect Of Exposure To Long Working Hours On Stroke: A Systematic Review And Meta-Analysis From The Who/Ilo Joint Estimates Of The Work-Related Burden Of Disease And Injury, Alexis Descatha, Bradley A Evanoff, Et Al

Open Access Publications

BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing joint estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates), with contributions from a large network of individual experts. Evidence from mechanistic data and prior studies suggests that exposure to long working hours may cause stroke. In this paper, we present a systematic review and meta-analysis of parameters for estimating the number of deaths and disability-adjusted life years from stroke that are attributable to exposure to long working hours, for the development of the WHO/ILO Joint Estimates.

OBJECTIVES: We aimed to systematically review …


Building Implementation Science In Nutrition, Andrea M. Warren, Edward A. Frongillo Jr., Rahul Rawat Sep 2020

Building Implementation Science In Nutrition, Andrea M. Warren, Edward A. Frongillo Jr., Rahul Rawat

Faculty Publications

The field of nutrition has been investing in the development of many nutrition-specific and -sensitive policies and programs aimed at improving population-level malnutrition in all its forms. When there is a need to learn about a new system, programmatic context, or target population to understand how to effectively deploy an intervention to help improve nutrition, it is important to be able to ask a broad range of questions, both in topic and in scope. Our aim is to provide a simple and conceptually clear definition and principles to elaborate the science of implementation for nutrition to distinguish it from other …


The Impact Of Narratives And Active Video Games On Long-Term Moderate-To-Vigorous Physical Activity: A Randomized Controlled Trial Protocol, Dar Alon, Caio Victor Sousa, Tom Baranowski, Tiago V Barreira, Romina Cabrera-Perez, Kelly Chiu, Austin Fernandez, Amy Fleischman, Shirley Huang, Jungyun Hwang, Melanie C Green, I-Min Lee, Kelly Lee, Sarah Lessard, Lynne L Levitsky, Aika Misawa, Farzad Noubary, Ronald Samuels, Kyung Jin Sun, Debbe Thompson, Amy S Lu Sep 2020

The Impact Of Narratives And Active Video Games On Long-Term Moderate-To-Vigorous Physical Activity: A Randomized Controlled Trial Protocol, Dar Alon, Caio Victor Sousa, Tom Baranowski, Tiago V Barreira, Romina Cabrera-Perez, Kelly Chiu, Austin Fernandez, Amy Fleischman, Shirley Huang, Jungyun Hwang, Melanie C Green, I-Min Lee, Kelly Lee, Sarah Lessard, Lynne L Levitsky, Aika Misawa, Farzad Noubary, Ronald Samuels, Kyung Jin Sun, Debbe Thompson, Amy S Lu

Children’s Nutrition Research Center Staff Publications

Background: Although physical activity (PA) has been shown in helping prevent and treat obesity, current PA interventions are still not effective in ameliorating the obesity epidemic. Additional forms of PA need to be investigated to improve PA engagement and outcomes. We hypothesize that pairing a narrative (i.e., story) with an active video game (AVG), a less traditional form of PA, will increase participant engagement in PA. This paper presents the rationale, implementation, and pilot results of a study assessing the effect of narrative's impact on PA and a series of other health outcomes.

Objective: This paper presents the rationale, implementation, …


The Vaso-Occlusive Pain Crisis In Sickle Cell Disease: Definition, Pathophysiology, And Management., Deepika S. Darbari, Vivien A. Sheehan, Samir K. Ballas Sep 2020

The Vaso-Occlusive Pain Crisis In Sickle Cell Disease: Definition, Pathophysiology, And Management., Deepika S. Darbari, Vivien A. Sheehan, Samir K. Ballas

Cardeza Foundation for Hematologic Research

Early diagnosis, treatment, and prevention of a vaso-occlusive crisis (VOC) are critical to the management of patients with sickle cell disease. It is essential to differentiate between VOC-associated pain and chronic pain, hyperalgesia, neuropathy, and neuropathic pain. The pathophysiology of VOCs includes polymerization of abnormal sickle hemoglobin, inflammation, and adhesion. Hydroxyurea, L-glutamine, crizanlizumab, and voxelotor have been approved by the US Food and Drug Administration for reducing the frequency of VOCs; the European Medicines Agency has approved only hydroxyurea. Other novel treatments are in late-stage clinical development in both the United States and the European Union. The development of agents …


Redesigning Nursing Education To Build Healthier Communities: An Innovative Cross-Sector Collaboration., Beth Ann Swan, Peggy Hilden, Nikki West, Garrett Chan, Kathryn Shaffer, Judith G Berg, Mary Dickow, Deloras Jones Sep 2020

Redesigning Nursing Education To Build Healthier Communities: An Innovative Cross-Sector Collaboration., Beth Ann Swan, Peggy Hilden, Nikki West, Garrett Chan, Kathryn Shaffer, Judith G Berg, Mary Dickow, Deloras Jones

College of Nursing Faculty Papers & Presentations

Today's health care environment requires registered nurses to be prepared for an array of practice settings, providing care outside the hospital and directly in the community. There is increasing focus on wellness, prevention, access to care, and mental health services for an aging and more diverse population. To improve alignment of education with increasingly complex needs, donor-advised funding supported four prelicensure nursing schools to transform their curricula. Selected schools were guided through a curriculum redesign process emphasizing community and continuum of care. This innovation was consistent with meeting challenges to realize the Institute of Medicine's 2011 Future of Nursing recommendations.


Parental Intent To Initiate And Complete The Human Papillomavirus Vaccine Series In The Usa: A Nationwide, Cross-Sectional Survey, Kalyani Sonawane, Yenan Zhu, Jane R Montealegre, David R Lairson, Cici Bauer, Lindy U Mcgee, Anna R Giuliano, Ashish A Deshmukh Sep 2020

Parental Intent To Initiate And Complete The Human Papillomavirus Vaccine Series In The Usa: A Nationwide, Cross-Sectional Survey, Kalyani Sonawane, Yenan Zhu, Jane R Montealegre, David R Lairson, Cici Bauer, Lindy U Mcgee, Anna R Giuliano, Ashish A Deshmukh

Faculty, Staff and Student Publications

BACKGROUND: Human papillomavirus (HPV) vaccine uptake among US adolescents is primarily dependent on the intent of their parents. to the best of our knowledge, an analysis quantifying parental intent to initiate and complete the HPV vaccine series in the USA at both the national and state level has not been done. We aim to estimate parental intent to initiate and complete the HPV vaccine series at the national-level and state-level and to identify reasons for lack of intent to initiate and complete the vaccine series.

METHODS: This cross-sectional study uses data from the adolescent component of the 2017-18 National Immunization …


Association Of Guideline Publication And Delays To Treatment In Pediatric Status Epilepticus, Iván Sánchez Fernández, Réjean M Guerriero, Et Al Sep 2020

Association Of Guideline Publication And Delays To Treatment In Pediatric Status Epilepticus, Iván Sánchez Fernández, Réjean M Guerriero, Et Al

Open Access Publications

OBJECTIVE: To determine whether publication of evidence on delays in time to treatment shortens time to treatment in pediatric refractory convulsive status epilepticus (rSE), we compared time to treatment before (2011-2014) and after (2015-2019) publication of evidence of delays in treatment of rSE in the Pediatric Status Epilepticus Research Group (pSERG) as assessed by patient interviews and record review.

METHODS: We performed a retrospective analysis of a prospectively collected dataset from June 2011 to September 2019 on pediatric patients (1 month-21 years of age) with rSE.

RESULTS: We studied 328 patients (56% male) with median (25th-75th percentile [p

CONCLUSION: Publication …


Aadc Deficiency From Infancy To Adulthood: Symptoms And Developmental Outcome In An International Cohort Of 63 Patients, Toni S Pearson, Laura Gilbert, Kathleen D Meeks, Et Al. Sep 2020

Aadc Deficiency From Infancy To Adulthood: Symptoms And Developmental Outcome In An International Cohort Of 63 Patients, Toni S Pearson, Laura Gilbert, Kathleen D Meeks, Et Al.

2020-Current year OA Pubs

Aromatic l-amino acid decarboxylase deficiency (AADCD) is a rare, autosomal recessive neurodevelopmental disorder characterized by impaired synthesis of dopamine, noradrenaline, adrenaline and serotonin, leading to a complex syndrome of motor, behavioral, and autonomic symptoms. This retrospective study assessed the symptoms and developmental outcome of a large international cohort of patients with AADCD via physician and/or caregiver responses to a detailed, standardized questionnaire. Sixty-three patients (60% female; ages 6 months-36 years, median 7 years; 58 living) from 23 individual countries participated. Common symptoms at onset (median age 3 months, range 0-12 months) were hypotonia, developmental delay, and/or oculogyric crises. Oculogyric crises …


How Do I Manage Long-Term Blood Component Shortages In A Hospital Transfusion Service, Claudia S. Cohn, Monica B. Pagano, Elizabeth S. Allen, Kathrine P. Frey, Thomas Gniadek, Parvez M. Lokhandwala, Colin H. Murphy, Jay S. Raval, Nancy M. Dunbar Sep 2020

How Do I Manage Long-Term Blood Component Shortages In A Hospital Transfusion Service, Claudia S. Cohn, Monica B. Pagano, Elizabeth S. Allen, Kathrine P. Frey, Thomas Gniadek, Parvez M. Lokhandwala, Colin H. Murphy, Jay S. Raval, Nancy M. Dunbar

Pathology Research and Scholarship

INTRODUCTION Temporary blood component shortages are common in some areas of the United States (US) and can usually be managed with short-term solutions.1However, a widespread, long-term shortage that leaves the blood industry with insufficient blood components to serve urgent medical needs requires additional mitigation strategies. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that caused the Coronavirus Disease 2019 (COVID-19) pandemic represents the greatest threat to the blood supply in recent memory. If the COVID-19 pandemic continues unchecked, the downward trend in blood collections will likely con-tinue.2Hospital transfusion services may be faced with unprecedented long-term shortages in blood products. A …


Integrating Quality Improvement Into The Echo Model To Improve Care For Children And Youth With Epilepsy, Sucheta Joshi, Kari Gali, Linda Radecki, Amy Shah, Sarah Hueneke, Trisha Calabrese, Alexis Katzenbach, Ramesh Sachdeva, Lawrence Brown, Eve Kimball, Patience White, Peggy Mcmanus, David Wood, Eve-Lynn Nelson, Pattie Archuleta Sep 2020

Integrating Quality Improvement Into The Echo Model To Improve Care For Children And Youth With Epilepsy, Sucheta Joshi, Kari Gali, Linda Radecki, Amy Shah, Sarah Hueneke, Trisha Calabrese, Alexis Katzenbach, Ramesh Sachdeva, Lawrence Brown, Eve Kimball, Patience White, Peggy Mcmanus, David Wood, Eve-Lynn Nelson, Pattie Archuleta

Project ECHO Bibliography

OBJECTIVE: Project ECHO (Extension for Community Healthcare Outcomes), a telementoring program, utilizes lectures, case-based learning, and an "all teach-all learn" approach to increase primary care provider (PCP) knowledge/confidence in managing chronic health conditions. The American Academy of Pediatrics (AAP) Epilepsy and Comorbidities ECHO incorporated quality improvement (QI) methodology to create meaningful practice change, while increasing PCP knowledge/self-efficacy in epilepsy management using the ECHO model.

METHODS: Monthly ECHO sessions (May 2018 to December 2018) included lectures, case presentations/discussion, and QI review. Pediatric practices were recruited through the AAP. Practices engaged in ECHO sessions and improvement activities including monthly Plan-Do-Study-Act cycles, team …


Covid-19 And Telehealth, Education, And Research Adaptations., N Romesh Wijesooriya, Vimal Mishra, Paul L P Brand, Bruce K Rubin Sep 2020

Covid-19 And Telehealth, Education, And Research Adaptations., N Romesh Wijesooriya, Vimal Mishra, Paul L P Brand, Bruce K Rubin

Project ECHO Bibliography

For decades, there have been government funded services to provide healthcare telephonically to remote sites both on the earth and in the air. This capability has evolved into what we now know as telehealth. The use of telehealth dramatically accelerated as a result of concerns for patient and healthcare provider safety during the SARS-CoV2 pandemic. Similarly, concerns regarding transmission of infection have required medical schools to provide robust, easily accessible virtual education options. At short notice, faculties have had to develop new telehealth focused curriculum components. However, telehealth, online education, and internet enabled research should not be simply a new …


Covid-19: Postmortem Diagnostic And Biosafety Considerations, J Matthew Lacy, Erin G. Brooks, Joshua Akers, Danielle Armstrong, Lauren Decker, Adam Gonzalez, William Humphrey, Romana Mayer, Matthew Miller, Catherine Perez, Jose Antonio Ruiz Arango, Lakshmanan Sathyavagiswaran, Wendy Stroh, Suzanne Utley Sep 2020

Covid-19: Postmortem Diagnostic And Biosafety Considerations, J Matthew Lacy, Erin G. Brooks, Joshua Akers, Danielle Armstrong, Lauren Decker, Adam Gonzalez, William Humphrey, Romana Mayer, Matthew Miller, Catherine Perez, Jose Antonio Ruiz Arango, Lakshmanan Sathyavagiswaran, Wendy Stroh, Suzanne Utley

Pathology Research and Scholarship

As a result of the 2019 novel human coronavirus (COVID-19) global spread, medical examiner/coroner offices will inevitably encounter increased numbers of COVID-19-infected decedents at autopsy. While in some cases a history of fever and/or respiratory distress (eg, cough or shortness of breath) may suggest the diagnosis, epidemiologic studies indicate that the majority of individuals infected with COVID-19 develop mild to no symptoms. Those dying with-but not of-COVID-19 may still be infectious, however. While multiple guidelines have been issued regarding autopsy protocol in cases of suspected COVID-19 deaths, there is some variability in the recommendations. Additionally, limited recommendations to date have …


Postmortem Computed Tomography In Firearm Homicides: A Retrospective Case Series, Marloes E M Vester, Kurt B Nolte, Gary M. Hatch, Chandra Y. Gerrard, Reinoud D. Stoel, Rick R. Van Rijn Sep 2020

Postmortem Computed Tomography In Firearm Homicides: A Retrospective Case Series, Marloes E M Vester, Kurt B Nolte, Gary M. Hatch, Chandra Y. Gerrard, Reinoud D. Stoel, Rick R. Van Rijn

Pathology Research and Scholarship

Postmortem computed tomography (PMCT) is integrated into the evaluation of decedents in several American medical examiner offices and medicolegal death investigative centers in many other countries. We retrospectively investigated the value of PMCT in a series of firearm homicide cases from a statewide centralized medical examiner's office that occurred during 2016. Autopsies were performed or supervised by board-certified forensic pathologists who reviewed the PMCT scans prior to autopsy. PMCT scans were re-evaluated by a forensic radiologist blinded to the autopsy findings and scored by body region (head-neck, thoracoabdominal, and extremities). Injury discrepancies were scored using a modified Goldman classification and …


Minimizing Surgical Blood Loss At Cesarean Hysterectomy For Placenta Previa With Evidence Of Placenta Increta Or Placenta Percreta: The State Of Play In 2020, John C. Kingdom, Sebastian R. Hobson, Ally Murji, Lisa Allen, Rory C. Windrim, Evelyn Lockhart, Sally L. Collins, Hooman Soleymani Majd, Moiad Alazzam, Feras Naaisa, Alireza A. Shamshirsaz, Michael A. Belfort, Karin A. Fox Sep 2020

Minimizing Surgical Blood Loss At Cesarean Hysterectomy For Placenta Previa With Evidence Of Placenta Increta Or Placenta Percreta: The State Of Play In 2020, John C. Kingdom, Sebastian R. Hobson, Ally Murji, Lisa Allen, Rory C. Windrim, Evelyn Lockhart, Sally L. Collins, Hooman Soleymani Majd, Moiad Alazzam, Feras Naaisa, Alireza A. Shamshirsaz, Michael A. Belfort, Karin A. Fox

Pathology Research and Scholarship

The evolution of multidisciplinary team-based care for women with placenta accreta spectrum disorder has delivered stepwise improvements in clinical outcomes. Central to this overall goal is the ability to limit blood loss at surgery. Placement of inflatable balloons within the pelvic arteries, most commonly in the anterior divisions of the internal iliac arteries, became popular in many centers, at the expense of prolonging surgical care and with attendant risks of vascular injury. In tandem, the need to expose pelvic sidewall anatomy to safely identify the course of the ureters re-popularized the alternative strategy of ligating the same anterior divisions of …


Complete Chemical Structures Of Human Mitochondrial Trnas, Takeo Suzuki, Yuka Yashiro, Ittoku Kikuchi, Yuma Ishigami, Hironori Saito, Ikuya Matsuzawa, Shunpei Okada, Mari Mito, Shintaro Iwasaki, Ding Ma, Xuewei Zhao, Kana Asano, Huan Lin, Yohei Kirino, Yuriko Sakaguchi, Tsutomu Suzuki Aug 2020

Complete Chemical Structures Of Human Mitochondrial Trnas, Takeo Suzuki, Yuka Yashiro, Ittoku Kikuchi, Yuma Ishigami, Hironori Saito, Ikuya Matsuzawa, Shunpei Okada, Mari Mito, Shintaro Iwasaki, Ding Ma, Xuewei Zhao, Kana Asano, Huan Lin, Yohei Kirino, Yuriko Sakaguchi, Tsutomu Suzuki

Computational Medicine Center Faculty Papers

Mitochondria generate most cellular energy via oxidative phosphorylation. Twenty-two species of mitochondrial (mt-)tRNAs encoded in mtDNA translate essential subunits of the respiratory chain complexes. mt-tRNAs contain post-transcriptional modifications introduced by nuclear-encoded tRNA-modifying enzymes. They are required for deciphering genetic code accurately, as well as stabilizing tRNA. Loss of tRNA modifications frequently results in severe pathological consequences. Here, we perform a comprehensive analysis of post-transcriptional modifications of all human mt-tRNAs, including 14 previously-uncharacterized species. In total, we find 18 kinds of RNA modifications at 137 positions (8.7% in 1575 nucleobases) in 22 species of human mt-tRNAs. An up-to-date list of 34 …


Immune And Microrna Responses To Infection And Indole-3-Carbinol During Colitis, Rasha Raheem Alkarkoushi, Yvonne Hui, Abbas S. Tavakoli, Udai Singh, Prakash Nagarkatti, Mitzi Nagarkatti, Ioulia Chatzistamou, Marpe Bam, Traci L. Testerman Aug 2020

Immune And Microrna Responses To Infection And Indole-3-Carbinol During Colitis, Rasha Raheem Alkarkoushi, Yvonne Hui, Abbas S. Tavakoli, Udai Singh, Prakash Nagarkatti, Mitzi Nagarkatti, Ioulia Chatzistamou, Marpe Bam, Traci L. Testerman

Faculty Publications

BACKGROUND: Indole-3-carbinol (I3C) and other aryl hydrocarbon receptor agonists are known to modulate the immune system and ameliorate various inflammatory and autoimmune diseases in animal models, including colitis induced by dextran sulfate sodium (DSS). MicroRNAs (miRNAs) are also gaining traction as potential therapeutic agents or diagnostic elements. Enterohepatic (EHH) species are associated with an increased risk of inflammatory bowel disease, but little is known about how these species affect the immune system or response to treatment. AIM: To determine whether infection with an EHH species alters the response to I3C and how the immune and miRNA responses of an EHH …


Regional Correlation Of Biochemical Measures Of Amyloid And Tau Phosphorylation In The Brain, Kanta Horie, Nicolas R Barthélemy, Nipun Mallipeddi, Yan Li, Erin E Franklin, Richard J Perrin, Randall J Bateman, Chihiro Sato Aug 2020

Regional Correlation Of Biochemical Measures Of Amyloid And Tau Phosphorylation In The Brain, Kanta Horie, Nicolas R Barthélemy, Nipun Mallipeddi, Yan Li, Erin E Franklin, Richard J Perrin, Randall J Bateman, Chihiro Sato

2020-Current year OA Pubs

Alzheimer's disease (AD) neuropathologic change is characterized by amyloid plaques and neurofibrillary tangles (NFTs) that consist of aggregated amyloid beta (Abeta) and hyperphosphorylated tau proteins (p-tau), respectively. Although the global relationship between Abeta and p-tau has been studied for decades, it is still unclear whether a regional correlation exists between Abeta and p-tau in the human brain. Recent studies in cerebrospinal fluid (CSF) have suggested that tau phosphorylation at specific sites such as T217 is modified at an early stage of AD when amyloid plaques become detectable. We applied biochemical and mass spectrometry methods in human brain samples with and …


Teaching Diagnostic Reasoning To Faculty Using An Assessment For Learning Tool: Training The Trainer, Adam Cohen, Moushumi Sur, Martin Weisse, Kathryn Moffett, Jeffrey Lancaster, Renee Saggio, Geeta Singhal, Satid Thammasitboon Aug 2020

Teaching Diagnostic Reasoning To Faculty Using An Assessment For Learning Tool: Training The Trainer, Adam Cohen, Moushumi Sur, Martin Weisse, Kathryn Moffett, Jeffrey Lancaster, Renee Saggio, Geeta Singhal, Satid Thammasitboon

Faculty, Staff and Students Publications

INTRODUCTION: There is a need for a standardized approach to understand and assess clinical reasoning in medical learners. The Assessment of Reasoning Tool was developed based on prevalent theories and frameworks using a multidisciplinary expert panel. As the tool provides a standardized rubric for assessing clinical reasoning, we designed an interactive train-the-trainer workshop for clinical educators and education leaders interested in improving their teaching skills and/or introducing curricula surrounding diagnostic reasoning.

METHODS: In this workshop, participants were exposed to the major domains of diagnostic reasoning and how to apply it to the assessment of a learner's skills. Kolb's experiential learning …


Structure And Mechanism Of A Unique Diiron Center In Mammalian Stearoyl-Coa Desaturase, Jiemin Shen, Gang Wu, Ah-Lim Tsai, Ming Zhou Aug 2020

Structure And Mechanism Of A Unique Diiron Center In Mammalian Stearoyl-Coa Desaturase, Jiemin Shen, Gang Wu, Ah-Lim Tsai, Ming Zhou

Faculty, Staff and Students Publications

Stearoyl-CoA desaturase 1 (SCD1) is a membrane-embedded metalloenzyme that catalyzes formation of a double-bond on a saturated acyl-CoA. SCD1 has a diiron center and its proper function requires an electron transport chain composed of NADH (or NADPH), cytochrome b5 reductase (b5R), and cytochrome b5 (cyt b5). Since SCD1 is a key regulator in fat metabolism and is required for survival of cancer cells, there is intense interest in targeting SCD1 for various metabolic diseases and cancers. Crystal structures of human and mouse SCD1 were reported recently, however, both proteins have two zinc ions instead of two iron ions in the …


Interstage Home Monitoring For Infants With Single Ventricle Heart Disease: Education And Management: A Scientific Statement From The American Heart Association., Nancy A. Rudd, Nancy S. Ghanayem, Garick D. Hill, Linda M. Lambert, Kathleen A. Mussatto, Jo Ann Nieves, Sarah Robinson, Girish S. Shirali, Michelle M. Steltzer, Karen Uzark, Nancy A. Pike, American Heart Association Council On Cardiovascular And Stroke Nursing; Council On Lifelong Congenital Heart Disease And Heart Health In The Young; Council On Arteriosclerosis, Thrombosis And Vascular Biology; Council On Clinical Cardiology; And Council On Lifestyle And Cardiometabolic Health Aug 2020

Interstage Home Monitoring For Infants With Single Ventricle Heart Disease: Education And Management: A Scientific Statement From The American Heart Association., Nancy A. Rudd, Nancy S. Ghanayem, Garick D. Hill, Linda M. Lambert, Kathleen A. Mussatto, Jo Ann Nieves, Sarah Robinson, Girish S. Shirali, Michelle M. Steltzer, Karen Uzark, Nancy A. Pike, American Heart Association Council On Cardiovascular And Stroke Nursing; Council On Lifelong Congenital Heart Disease And Heart Health In The Young; Council On Arteriosclerosis, Thrombosis And Vascular Biology; Council On Clinical Cardiology; And Council On Lifestyle And Cardiometabolic Health

Manuscripts, Articles, Book Chapters and Other Papers

This scientific statement summarizes the current state of knowledge related to interstage home monitoring for infants with shunt-dependent single ventricle heart disease. Historically, the interstage period has been defined as the time of discharge from the initial palliative procedure to the time of second stage palliation. High mortality rates during the interstage period led to the implementation of in-home surveillance strategies to detect physiologic changes that may precede hemodynamic decompensation in interstage infants with single ventricle heart disease. Adoption of interstage home monitoring practices has been associated with significantly improved morbidity and mortality. This statement will review in-hospital readiness for …


Periacetabular Osteotomy With Or Without Arthroscopic Management In Patients With Hip Dysplasia: Study Protocol For A Multicenter Randomized Controlled Trial, Geoffrey P Wilkin, Stéphane Poitras, John Clohisy, Etienne Belzile, Ira Zaltz, George Grammatopoulos, Gerd Melkus, Kawan Rakhra, Tim Ramsay, Kednapa Thavorn, Paul E Beaulé Aug 2020

Periacetabular Osteotomy With Or Without Arthroscopic Management In Patients With Hip Dysplasia: Study Protocol For A Multicenter Randomized Controlled Trial, Geoffrey P Wilkin, Stéphane Poitras, John Clohisy, Etienne Belzile, Ira Zaltz, George Grammatopoulos, Gerd Melkus, Kawan Rakhra, Tim Ramsay, Kednapa Thavorn, Paul E Beaulé

2020-Current year OA Pubs

BACKGROUND: Hip dysplasia is one of the most common causes of hip arthritis. Its incidence is estimated to be between 3.6 and 12.8% (Canadian Institute for Health Information, Hip and knee replacements in Canada, 2017-2018: Canadian joint replacement registry annual report, 2019; Jacobsen and Sonne-Holm, Rheumatology 44:211-8, 2004). The Periacetabular Osteotomy (PAO) has been used successfully for over 30 years (Gosvig et al., J Bone Joint Surg Am 92:1162-9, 2010), but some patients continue to exhibit symptoms post-surgery (Wyles et al., Clin Orthop Relat Res 475:336-50, 2017). A hip arthroscopy, performed using a small camera, allows surgeons to address torn …


Genomic Characterization Of Malignant Progression In Neoplastic Pancreatic Cysts, Michaël Noë, Noushin Niknafs, Catherine G Fischer, Wenzel M Hackeng, Violeta Beleva Guthrie, Waki Hosoda, Marija Debeljak, Eniko Papp, Vilmos Adleff, James R White, Claudio Luchini, Antonio Pea, Aldo Scarpa, Giovanni Butturini, Giuseppe Zamboni, Paola Castelli, Seung-Mo Hong, Shinichi Yachida, Nobuyoshi Hiraoka, Anthony J Gill, Jaswinder S Samra, G Johan A Offerhaus, Anne Hoorens, Joanne Verheij, Casper Jansen, N Volkan Adsay, Wei Jiang, Jordan Winter, Jorge Albores-Saavedra, Benoit Terris, Elizabeth D Thompson, Nicholas J Roberts, Ralph H Hruban, Rachel Karchin, Robert B Scharpf, Lodewijk A A Brosens, Victor E Velculescu, Laura D Wood Aug 2020

Genomic Characterization Of Malignant Progression In Neoplastic Pancreatic Cysts, Michaël Noë, Noushin Niknafs, Catherine G Fischer, Wenzel M Hackeng, Violeta Beleva Guthrie, Waki Hosoda, Marija Debeljak, Eniko Papp, Vilmos Adleff, James R White, Claudio Luchini, Antonio Pea, Aldo Scarpa, Giovanni Butturini, Giuseppe Zamboni, Paola Castelli, Seung-Mo Hong, Shinichi Yachida, Nobuyoshi Hiraoka, Anthony J Gill, Jaswinder S Samra, G Johan A Offerhaus, Anne Hoorens, Joanne Verheij, Casper Jansen, N Volkan Adsay, Wei Jiang, Jordan Winter, Jorge Albores-Saavedra, Benoit Terris, Elizabeth D Thompson, Nicholas J Roberts, Ralph H Hruban, Rachel Karchin, Robert B Scharpf, Lodewijk A A Brosens, Victor E Velculescu, Laura D Wood

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are non-invasive neoplasms that are often observed in association with invasive pancreatic cancers, but their origins and evolutionary relationships are poorly understood. In this study, we analyze 148 samples from IPMNs, MCNs, and small associated invasive carcinomas from 18 patients using whole exome or targeted sequencing. Using evolutionary analyses, we establish that both IPMNs and MCNs are direct precursors to pancreatic cancer. Mutations in SMAD4 and TGFBR2 are frequently restricted to invasive carcinoma, while RNF43 alterations are largely in non-invasive lesions. Genomic analyses suggest an average window of over three …