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Multiomics Characterization Of Preterm Birth In Low- And Middle-Income Countries., Fyezah Jehan, Sunil Sazawal, Abdullah H. Baqui, Muhammad Imran Nisar, Usha Dhingra, Rasheda Khanam, Muhammad Ilyas, Arup Dutta, Dipak K. Mitra, Usma Mehmood, Saikat Deb, Arif Mahmud, Aneeta Hotwani, Said Mohammed Ali, Sayedur Rahman, Ambreen Nizar, Shaali Makame Ame, Mamun Ibne Moin, Sajid Muhammad, Aishwarya Chauhan, Nazma Begum, Waqasuddin Khan, Sayan Das, Salahuddin Ahmed, Tarik Hasan, Javairia Khalid, Syed Jafar Raza Rizvi, Mohammed Hamad Juma, Nabidul Haque Chowdhury, Furqan Kabir, Fahad Aftab, Abdul Quaiyum, Alexander Manu, Sachiyo Yoshida, Rajiv Bahl, Anisur Rahman, Jesmin Pervin, Jennifer Winston, Patrick Musonda, Jeffrey S. A. Stringer, James A. Litch, Mohammad Sajjad Ghaemi, Mira N. Moufarrej, Kévin Contrepois, Songjie Chen, Ina A. Stelzer, Natalie Stanley, Alan L. Chang, Ghaith Bany Hammad, Ronald J. Wong, Candace Liu, Cecele C. Quaintance, Anthony Culos, Camilo Espinosa, Maria Xenochristou, Martin Becker, Ramin Fallahzadeh, Edward Ganio, Amy S. Tsai, Dyani Gaudilliere, Eileen S. Tsai, Xiaoyuan Han, Kazuo Ando, Martha Tingle, Ivana Maric, Paul H. Wise, Virginia D. Winn, Maurice L. Druzin, Ronald S. Gibbs, Gary L. Darmstadt, Jeffrey C. Murray, Gary M. Shaw, David K. Stevenson, Michael P. Snyder, Stephen R. Quake, Martin S. Angst, Brice Gaudilliere, Nima Aghaeepour

All Dugoni School of Dentistry Faculty Articles

Importance: Worldwide, preterm birth (PTB) is the single largest cause of deaths in the perinatal and neonatal period and is associated with increased morbidity in young children. The cause of PTB is multifactorial, and the development of generalizable biological models may enable early detection and guide therapeutic studies.

Objective: To investigate the ability of transcriptomics and proteomics profiling of plasma and metabolomics analysis of urine to identify early biological measurements associated with PTB.

Design, Setting, and Participants: This diagnostic/prognostic study analyzed plasma and urine samples collected from May 2014 to June 2017 from pregnant women in 5 biorepository cohorts in …

A Study Protocol For A Multicentre, Prospective, Before-And-After Trial Evaluating The Feasibility Of Implementing Targeted Sedation After Initiation Of Mechanical Ventilation In The Emergency Department (The Ed-Sed Pilot Trial), Brian M Fuller, Brian W Roberts, Nicholas M Mohr, Ryan D Pappal, Robert J Stephens, Yan Yan, Chris Carpenter, Marin H Kollef, Michael Simon Avidan

Open Access Publications

INTRODUCTION: Sedation is a cornerstone therapy in the management of patients receiving mechanical ventilation and is highly influential on outcome. Early sedation depth appears especially influential, as early deep sedation is associated with worse outcome when compared with light sedation. Our research group has shown that patients receiving mechanical ventilation in the emergency department (ED) are exposed to deep sedation commonly, and ED sedation depth is impactful on intensive care unit (ICU) care and clinical outcomes. While extensive investigation has occurred for patients in the ICU, comparatively little data exist from the ED. Given the influence that ED sedation seems …

Associations Between Atrial Cardiopathy And Cerebral Amyloid: The Aric-Pet Study, Michelle C Johansen, Thomas H Mosley, David S Knopman, Dean F Wong, Chiadi Ndumele, Amil M Shah, Scott D Solomon, Rebecca F Gottesman

Open Access Publications

Background Atrial fibrillation (AF) is a risk factor for cognitive decline, possibly from silent brain infarction. Left atrial changes in structure or function (atrial cardiopathy) can lead to AF but may impact cognition independently. It is unknown if AF or atrial cardiopathy also acts on Alzheimer disease-specific mechanisms, such as deposition of β-amyloid. Methods and Results A total of 316 dementia-free participants from the ARIC (Atherosclerosis Risk in Communities) study underwent florbetapir positron emission tomography, electrocardiography, and 2-dimensional echocardiography. Atrial cardiopathy was defined as ≥1: (1) left atrial volume index >34 mL/m

Conversational Ontology Operator: Patient-Centric Vaccine Dialogue Management Engine For Spoken Conversational Agents, Muhammad Amith, Rebecca Z Lin, Licong Cui, Dennis Wang, Anna Zhu, Grace Xiong, Hua Xu, Kirk Roberts, Cui Tao

2020-Current year OA Pubs

BACKGROUND: Previously, we introduced our Patient Health Information Dialogue Ontology (PHIDO) that manages the dialogue and contextual information of the session between an agent and a health consumer. In this study, we take the next step and introduce the Conversational Ontology Operator (COO), the software engine harnessing PHIDO. We also developed a question-answering subsystem called Frankenstein Ontology Question-Answering for User-centric Systems (FOQUS) to support the dialogue interaction.

METHODS: We tested both the dialogue engine and the question-answering system using application-based competency questions and questions furnished from our previous Wizard of OZ simulation trials.

RESULTS: Our results revealed that the dialogue …

Protocol For The Prognosticating Delirium Recovery Outcomes Using Wakefulness And Sleep Electroencephalography (P-Drows-E) Study: A Prospective Observational Study Of Delirium In Elderly Cardiac Surgical Patients, S Kendall Smith, Thomas Nguyen, Alyssa K Labonte, Mohammadmehdi Kafashan, Orlandrea Hyche, Christian S Guay, Elizabeth Wilson, Courtney W Chan, Anhthi Luong, L Brian Hickman, Bradley A Fritz, Daniel Emmert, Thomas J Graetz, Spencer J Melby, Brendan P Lucey, Yo-El S Ju, Troy S Wildes, Michael S Avidan, Ben J A Palanca

Open Access Publications

INTRODUCTION: Delirium is a potentially preventable disorder characterised by acute disturbances in attention and cognition with fluctuating severity. Postoperative delirium is associated with prolonged intensive care unit and hospital stay, cognitive decline and mortality. The development of biomarkers for tracking delirium could potentially aid in the early detection, mitigation and assessment of response to interventions. Because sleep disruption has been posited as a contributor to the development of this syndrome, expression of abnormal electroencephalography (EEG) patterns during sleep and wakefulness may be informative. Here we hypothesise that abnormal EEG patterns of sleep and wakefulness may serve as predictive and diagnostic …

Whole Health Options And Pain Education (Whope): A Pragmatic Trial Comparing Whole Health Team Vs Primary Care Group Education To Promote Nonpharmacological Strategies To Improve Pain, Functioning, And Quality Of Life In Veterans-Rationale, Methods, And Implementation, Karen H Seal, Kavitha Reddy, Et Al.

2020-Current year OA Pubs

BACKGROUND: The Whole Health model of the U.S. Department of Veterans Affairs (VA) emphasizes holistic self-care and multimodal approaches to improve pain, functioning, and quality of life. wHOPE (Whole Health Options and Pain Education) seeks to be the first multisite pragmatic trial to establish evidence for the VA Whole Health model for chronic pain care.

DESIGN: wHOPE is a pragmatic randomized controlled trial comparing a Whole Health Team (WHT) approach to Primary Care Group Education (PC-GE); both will be compared to Usual VA Primary Care (UPC). The WHT consists of a medical provider, a complementary and integrative health (CIH) provider, …

Evaluating The Implementation Of The Switch® School Wellness Intervention And Capacity-Building Process Through Multiple Methods, Gabriella M Mcloughlin, Priscila Candal, Spyridoula Vazou, Joey A Lee, David A Dzewaltowski, Richard R Rosenkranz, Lorraine Lanningham-Foster, Douglas A Gentile, Laura Liechty, Senlin Chen, Gregory J Welk

2020-Current year OA Pubs

BACKGROUND: School wellness programming is important for promoting healthy lifestyles and academic achievement in youth; however, research is needed on methods that can help schools implement and sustain such programs on their own. The purpose of this study was to investigate factors within and outside the school environment that influenced school capacity for implementation and potential sustainability of wellness programming.

METHODS: As part of the School Wellness Integration Targeting Child Health (SWITCH®) intervention, elementary school wellness teams (N = 30) were guided through a capacity-building process focused on promoting the adoption of healthy lifestyle behaviors in students. Data on implementation …

Medicine And Surgery Residents' Perspectives On The Impact Of Covid-19 On Graduate Medical Education., Tanvi Rana, Christopher Hackett, Timothy Quezada, Abhishek Chaturvedi, Veli Bakalov, Jody Leonardo, Sandeep Rana

COVID-19 Papers, Posters, and Presentations

The COVID-19 crisis has had an unprecedented impact on resident education and well-being: social distancing guidelines have limited patient volumes and forced virtual learning, while personal protective equipment (PPE) shortages, school/daycare closures, and visa restrictions have served as additional stressors. Our study aimed to analyze the effects of COVID-19 crisis-related stressors on residents' professional and personal lives. In April 2020, we administered a survey to residents at a large academic hospital system in order to assess the impact of the pandemic on residency training after >6 weeks of a modified schedule. The primary outcome was to determine which factors or …

Adverse Event Reporting For Cellular Therapy Products: Current Status And Future Directions, Kathy Loper, Michele W. Sugrue, Jay S. Raval, Joseph Yossi Schwartz, Kevin Land, Mickey Koh, Thilo Mengling, Hildegard Greinix, Jörg P. Halter, Christina M Celluzzi, Maysum Chaudhri

Pathology Research and Scholarship

Adverse event (AE) and adverse reaction (AR) reporting are key components of patient safety and surveillance systems. Review and analysis of this data yields opportunities for process improvement, product information and interventions, and can lead to improved patient outcomes and donor safety overall. AE and AR reporting for cellular therapy products is fragmented and not well characterized in a central reference. This review article, authored by experts from various organizations, serves to summarize the current state of reporting and offers opportunities for streamlining and coordination, as well as key reference for professionals in this field.

Development And Implementation Of A Healthcare Volunteer Retention Program, Sandra Gomez

Student Scholarly Projects

Practice Problem: Healthcare volunteer responders are an asset during disasters, and their retention is necessary to meet rising demands. This project aimed to develop and implement an evidence-based practice change using a healthcare volunteer retention program and evaluate its influence on retention.

PICOT: The PICOT question that guided this evidence-based practice project was: In healthcare volunteers, how does the participation in a formal healthcare volunteer retention program influence healthcare volunteer retention rate, intent to stay, and volunteer satisfaction 12 weeks after Healthcare Volunteer Retention Program introduction?

Evidence: The evidence from the literature supported mentoring, education and training, …

A Large-Scale Genome-Wide Association Study Meta-Analysis Of Cannabis Use Disorder, Emma C Johnson, Alexander S Hatoum, June He, Kathleen K Bucholz, Louis Fox, Sarah M Hartz, John P Rice, Nancy L Saccone, Laura J Bierut, Richard A Grucza, Andrew C Heath, Pamela A F Madden, Elliot C Nelson, Arpana Agrawal, Et Al.

2020-Current year OA Pubs

BACKGROUND: Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50-70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder.

METHODS: To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use …

Inferior St-Elevation Myocardial Infarction Presenting When Urgent Primary Percutaneous Coronary Intervention Is Unavailable: Should We Adhere To Current Guidelines?, Yochai Birnbaum, Glenn N Levine, John French, Juan Carlos Kaski, Dan Atar, Mahboob Alam, David Hasdai, Hani Jneid, Barry F Uretsky

Faculty, Staff and Students Publications

The pivotal studies that led to the recommendations for emergent reperfusion therapy for ST-elevation myocardial infarction (STEMI) were conducted for the most part over 25 years ago. At that time, contemporary standard treatments including aspirin, statin, and even anticoagulation were not commonly used. The 2013 American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) guidelines and the 2017 European Society of Cardiology guidelines give a class I recommendation (with the level of evidence A) for primary percutaneous coronary intervention (pPCI) in patients with STEMI and ischemic symptoms of less than 12 h. However, if the patient presents to a hospital …

Inferior St-Elevation Myocardial Infarction Presenting When Urgent Primary Percutaneous Coronary Intervention Is Unavailable: Should We Adhere To Current Guidelines?, Yochai Birnbaum, Glenn N Levine, John French, Juan Carlos Kaski, Dan Atar, Mahboob Alam, David Hasdai, Hani Jneid, Barry F Uretsky

Faculty, Staff and Students Publications

The pivotal studies that led to the recommendations for emergent reperfusion therapy for ST-elevation myocardial infarction (STEMI) were conducted for the most part over 25 years ago. At that time, contemporary standard treatments including aspirin, statin, and even anticoagulation were not commonly used. The 2013 American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) guidelines and the 2017 European Society of Cardiology guidelines give a class I recommendation (with the level of evidence A) for primary percutaneous coronary intervention (pPCI) in patients with STEMI and ischemic symptoms of less than 12 h. However, if the patient presents to a hospital …

Stat1 Dissociates Adipose Tissue Inflammation From Insulin Sensitivity In Obesity, Aaron R Cox, Natasha Chernis, David A Bader, Pradip K Saha, Peter M Masschelin, Jessica B Felix, Robert Sharp, Zeqin Lian, Vasanta Putluri, Kimal Rajapakshe, Kang Ho Kim, Dennis T Villareal, Reina Armamento-Villareal, Huaizhu Wu, Cristian Coarfa, Nagireddy Putluri, Sean M Hartig

Faculty, Staff and Students Publications

Obesity fosters low-grade inflammation in white adipose tissue (WAT) that may contribute to the insulin resistance that characterizes type 2 diabetes. However, the causal relationship of these events remains unclear. The established dominance of STAT1 function in the immune response suggests an obligate link between inflammation and the comorbidities of obesity. To this end, we sought to determine how STAT1 activity in white adipocytes affects insulin sensitivity. STAT1 expression in WAT inversely correlated with fasting plasma glucose in both obese mice and humans. Metabolomic and gene expression profiling established STAT1 deletion in adipocytes (STAT1a-KO) enhanced mitochondrial function …

Inflammatory Myopathies: Update On Diagnosis, Pathogenesis And Therapies, And Covid-19-Related Implications., Marinos C. Dalakas

Department of Neurology Faculty Papers

The inflammatory myopathies constitute a heterogeneous group of acquired myopathies that have in common the presence of endomysial inflammation. Based on steadily evolved clinical, histological and immunopathological features and some autoantibody associations, these disorders can now be classified in five characteristic subsets: Dermatomyositis (DM) Polymyositis (PM), Necrotizing Autoimmune Myositis (NAM), Anti-synthetase syndrome-overlap myositis (Anti-SS-OM), and Inclusion-Body-Myositis (IBM). Each inflammatory myopathy subset has distinct immunopathogenesis, prognosis and response to immunotherapies, necessitating the need to correctly identify each subtype from the outset to avoid disease mimics and proceed to early therapy initiation. The review presents the main clinicopathologic characteristics of each subset …

Addressing Health Disparities In The Rural United States: Advocacy As Caregiving Among Community Health Workers And Promotores De Salud, Ryan I Logan, Heide Castañeda

All publications

Rural populations in the United States are faced with a variety of health disparities that complicate access to care. Community health workers (CHWs) and their Spanish-speaking counterparts, promotores de salud, are well-equipped to address rural health access issues, provide education, and ultimately assuage these disparities. In this article, we compare community health workers in the states of Indiana and Texas, based on the results of two separate research studies, in order to (1) investigate the unique role of CHWs in rural communities and (2) understand how their advocacy efforts represent a central form of caregiving. Drawing on ethnographic, qualitative data—including …

The Cortico-Limbo-Thalamo-Cortical Circuits: An Update To The Original Papez Circuit Of The Human Limbic System, Jochen Profit, Paul J Sharek, Xin Cui, Courtney C Nisbet, Eric J Thomas, Daniel S Tawfik, Henry C Lee, David Draper, J Bryan Sexton

Faculty, Staff and Student Publications

OBJECTIVES: Key validated clinical metrics are being used individually and in aggregate (Baby-MONITOR) to monitor the performance of neonatal intensive care units (NICUs). The degree to which perceptions of key components of safety culture, safety climate, and teamwork are related to aspects of NICU quality of care is poorly understood. The objective of this study was to test whether NICU performance on key clinical metrics correlates with caregiver perceptions of safety culture.

STUDY DESIGN: Cross-sectional study of 6253 very low-birth-weight infants in 44 NICUs. We measured clinical quality via the Baby-MONITOR and its nine risk-adjusted and standardized subcomponents (antenatal corticosteroids, …

International Council For Standardization In Haematology (Icsh) Recommendations For Laboratory Measurement Of Adamts13, Ian Mackie, Ilaria Mancini, Joshua Muia, Johanna Kremer Hovinga, Sukesh Nair, Sam Machin, Ross Baker

2020-Current year OA Pubs

This guidance document was prepared on behalf of the International Council for Standardization in Haematology (ICSH), by the ADAMTS13 Assay Working Group, which comprises an international group of both clinical and laboratory experts. The document provides recommendations on best practice for the performance of ADAMTS13 assays in clinical laboratories. ADAMTS13 assays support the differential diagnosis of thrombotic microangiopathies and have utility in the management of thrombotic thrombocytopenic purpura (TTP). There are three types of assay: activity, antigen and autoantibody/inhibitor assays. Methods for activity assays differ in terms of sensitivity, specificity, precision and turnaround time. The most widely used assays involve …

Evolution Of The Epigenetic Landscape In Childhood B Acute Lymphoblastic Leukemia And Its Role In Drug Resistance, Shella Saint Fleur-Lominy, Nikki A. Evensen, Teena Bhatla, Gunjan Sethia, Sonali Narang, Jun H. Choi, Xiaotu Ma, Jun J. Yang, Stephen Kelly, Elizabeth Raetz, Richard C. Harvey, Cheryl Willman, Mignon L. Loh, Stephen P. Hunger, Patrick A. Brown, Kylie M. Getz, Cem Meydan, Christopher E. Mason, Aristotelis Tsirigos, William Carroll

Pathology Research and Scholarship

Although B-cell acute lymphoblastic leukemia (B-ALL) is the most common malignancy in children and while highly curable, it remains a leading cause of cancer-related mortality. The outgrowth of tumor subclones carrying mutations in genes responsible for resistance to therapy has led to a Darwinian model of clonal selection. Previous work has indicated that alterations in the epigenome might contribute to clonal selection, yet the extent to which the chromatin state is altered under the selective pressures of therapy is unknown. To address this, we performed chromatin immunoprecipitation, gene expression analysis, and enhanced reduced representation bisulfite sequencing on a cohort of …

Carfilzomib, Lenalidomide, And Dexamethasone Plus Transplant In Newly Diagnosed Multiple Myeloma, Jagoda K Jasielec, Ravi Vij, Et Al.

2020-Current year OA Pubs

In this phase 2 multicenter study, we evaluated the incorporation of autologous stem cell transplantation (ASCT) into a carfilzomib-lenalidomide-dexamethasone (KRd) regimen for patients with newly diagnosed multiple myeloma (NDMM). Transplant-eligible patients with NDMM received 4 cycles of KRd induction, ASCT, 4 cycles of KRd consolidation, and 10 cycles of KRd maintenance. The primary end point was rate of stringent complete response (sCR) after 8 cycles of KRd with a predefined threshold of ≥50% to support further study. Seventy-six patients were enrolled with a median age of 59 years (range, 40-76 years), and 35.5% had high-risk cytogenetics. The primary end point …

Social And Leisure Activities Predict Transitions In Cognitive Functioning In Older Mexican Adults: A Latent Transition Analysis Of The Mexican Health And Aging Study, Heather Mary Brown, Stephen A Murray, Hope Northrup, Kit Sing Au, Lee A Niswander

Faculty, Staff and Student Publications

Disruptions in neural tube (NT) closure result in neural tube defects (NTDs). To understand the molecular processes required for mammalian NT closure, we investigated the role of Snx3, a sorting nexin gene. Snx3−/− mutant mouse embryos display a fully-penetrant cranial NTD. In vivo, we observed decreased canonical WNT target gene expression in the cranial neural epithelium of the Snx3−/− embryos and a defect in convergent extension of the neural epithelium. Snx3−/− cells show decreased WNT secretion, and live cell imaging reveals aberrant recycling of the WNT ligand-binding protein WLS and mis-trafficking to the lysosome for degradation. The importance …

Functional Genomic Analyses Uncover Apoe-Mediated Regulation Of Brain And Cerebrospinal Fluid Beta-Amyloid Levels In Parkinson Disease, Laura Ibanez, Jorge A Bahena, Chengran Yang, Umber Dube, Fabiana H G Farias, John P Budde, Kristy Bergmann, Carol Brenner-Webster, John C Morris, Richard J Perrin, Nigel J Cairns, John O'Donnell, Rebecca Miller, Albert A Davis, Paul Kotzbauer, Meghan C Campbell, Joel S Perlmutter, Oscar Harari, Carlos Cruchaga, Bruno A Benitez, Et Al.

2020-Current year OA Pubs

Alpha-synuclein is the main protein component of Lewy bodies, the pathological hallmark of Parkinson's disease. However, genetic modifiers of cerebrospinal fluid (CSF) alpha-synuclein levels remain unknown. The use of CSF levels of amyloid beta

Full-Length Trkb Variant In Nsclc Is Associated With Brain Metastasis, Mariangela Lombardi, Michela D'Ascanio, Stefania Scarpino, Davide Scozzi, Marco Giordano, Leopoldo Costarelli, Enrico Rathina Raj, Rita Mancini, Giuseppe Cardillo, Vittorio Cardaci, Marta Innammorato, Andrea Vecchione, Alberto Ricci

Open Access Publications

Despite remarkable therapeutic advances have been made in the last few decades, non-small cell lung cancer (NSCLC) is still one of the leading causes of death worldwide. Brain metastases are a common complication of a wide range of human malignancies and in particular NSCLC. Brain-derived neurotrophic factor (BDNF), binding its high-affinity tyrosine kinase B receptor, has been shown to promote cancer progression and metastasis. We hereby investigated the expression of the BDNF and its TrkB receptor in its full-length and truncated isoform T1, in samples from primary adenocarcinomas (ADKs) of the lung and in their metastasis to evaluate if their …

Conduct Of Clinical Trials In The Era Of Covid-19: Jacc Scientific Expert Panel., Mitchell A. Psotka, William T. Abraham, Mona Fiuzat, Gerasimos Filippatos, Joann Lindenfeld, Tariq Ahmad, Ankeet S. Bhatt, Peter E. Carson, John G.F. Cleland, G. Michael Felker, James L. Januzzi, Dalane W. Kitzman, Eric S. Leifer, Eldrin F. Lewis, John J.V. Mcmurray, Robert J. Mentz, Scott D. Solomon, Norman Stockbridge, John R. Teerlink, Muthiah Vaduganathan, Orly Vardeny, David J. Whellan, Janet Wittes, Stefan D. Anker, Christopher M. O'Connor

Department of Medicine Faculty Papers

The coronavirus disease-2019 (COVID-19) pandemic has profoundly changed clinical care and research, including the conduct of clinical trials, and the clinical research ecosystem will need to adapt to this transformed environment. The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory and the Academic Research Consortium, composed of academic investigators from the United States and Europe, patients, the U.S. Food and Drug Administration, the National Institutes of Health, and industry members. A series of meetings were convened to address the challenges caused by the COVID-19 pandemic, review options for maintaining or altering best practices, and establish …

Ryanodine Receptor 1-Related Disorders: An Historical Perspective And Proposal For A Unified Nomenclature, Tokunbor A Lawal, Joshua J Todd, Jessica W Witherspoon, Carsten G Bönnemann, James J Dowling, Susan L Hamilton, Katherine G Meilleur, Robert T Dirksen

Faculty, Staff and Students Publications

The RYR1 gene, which encodes the sarcoplasmic reticulum calcium release channel or type 1 ryanodine receptor (RyR1) of skeletal muscle, was sequenced in 1988 and RYR1 variations that impair calcium homeostasis and increase susceptibility to malignant hyperthermia were first identified in 1991. Since then, RYR1-related myopathies (RYR1-RM) have been described as rare, histopathologically and clinically heterogeneous, and slowly progressive neuromuscular disorders. RYR1 variants can lead to dysfunctional RyR1-mediated calcium release, malignant hyperthermia susceptibility, elevated oxidative stress, deleterious post-translational modifications, and decreased RyR1 expression. RYR1-RM-affected individuals can present with delayed motor milestones, contractures, scoliosis, ophthalmoplegia, and respiratory insufficiency.Historically, RYR1-RM-affected individuals were …

Structural Basis Of Ion Transport And Inhibition In Ferroportin, Yaping Pan, Zhenning Ren, Shuai Gao, Jiemin Shen, Lie Wang, Zhichun Xu, Ye Yu, Preetham Bachina, Hanzhi Zhang, Xiao Fan, Arthur Laganowsky, Nieng Yan, Ming Zhou

Faculty, Staff and Students Publications

Ferroportin is an iron exporter essential for releasing cellular iron into circulation. Ferroportin is inhibited by a peptide hormone, hepcidin. In humans, mutations in ferroportin lead to ferroportin diseases that are often associated with accumulation of iron in macrophages and symptoms of iron deficiency anemia. Here we present the structures of the ferroportin from the primate Philippine tarsier (TsFpn) in the presence and absence of hepcidin solved by cryo-electron microscopy. TsFpn is composed of two domains resembling a clamshell and the structure defines two metal ion binding sites, one in each domain. Both structures are in an outward-facing conformation, and …

Maternal Hookworm Infection And Its Effects On Maternal Health: A Systematic Review And Meta-Analysis, Tara E Ness, Vedika Agrawal, Kathryn Bedard, Lara Ouellette, Timothy A Erickson, Peter Hotez, Jill E Weatherhead

Library Staff Publications

Hookworm is an intestinal parasite that infects nearly 230 million people, with another 5.1 billion at risk, especially in poverty-stricken tropical and subtropical regions. Pregnancy is an especially vulnerable time for hookworm infection because of its effect on both maternal and subsequently fetal health. A systematic review and meta-analysis was conducted. The meta-analysis was performed on the association between maternal hookworm and maternal anemia, as well as maternal hookworm coinfection with malaria. The prevalence of hookworm ranged from 1% to 78% in pregnant women, whereas malaria prevalence ranged from 11% to 81%. Pregnant women with hookworm infection were more likely …

How Parents And Their Children Used Social Media And Technology At The Beginning Of The Covid-19 Pandemic And Associations With Anxiety., Michelle Drouin, Brandon T. Mcdaniel Phd, Jessica Pater, Tammy Toscos Phd

Health Services and Informatics Research

In this study, we examined parents' (n = 260) perceptions of their own and their children's use of social media and other types of communication technologies in the beginning stages of coronavirus disease 2019 (COVID-19) related sanctions (e.g., social distancing) in the United States. We also examined associations between social media and technology use and anxiety. On average, parents reported that both they and their children (especially teenagers aged 13-18) had increased technology and social media use since the beginning of social distancing. Moreover, even after controlling for demographic factors, structural equation models showed that parents and children with …

Organizational Readiness Assessment In Acute And Long-Term Care Has Important Implications For Antibiotic Stewardship For Asymptomatic Bacteriuria, Melanie C Goebel, Barbara W Trautner, Yiqun Wang, John N Van, Laura M Dillon, Payal K Patel, Dimitri M Drekonja, Christopher J Graber, Bhavarth S Shukla, Paola Lichtenberger, Christian D Helfrich, Anne Sales, Larissa Grigoryan

Faculty, Staff and Students Publications

BACKGROUND: Prior to implementing an antibiotic stewardship intervention for asymptomatic bacteriuria (ASB), we assessed institutional barriers to change using the Organizational Readiness to Change Assessment.

METHODS: Surveys were self-administered on paper in inpatient medicine and long-term care units at 4 Veterans Affairs facilities. Participants included providers, nurses, and pharmacists. The survey included 7 subscales: evidence (perceived strength of evidence) and six context subscales (favorability of organizational context). Responses were scored on a 5-point Likert-type scale.

RESULTS: One hundred four surveys were completed (response rate = 69.3%). Overall, the evidence subscale had the highest score; the resources subscale (mean 2.8) was …

Donor And Transplant Candidate Selection For Solid Organ Transplantation During The Covid-19 Pandemic, N Thao N Galvan, Nicolas F Moreno, Jay E Garza, Susan Bourgeois, Marion Hemmersbach-Miller, Bhamidipati Murthy, Katherine Timmins, Christine A O'Mahony, James Anton, Andrew Civitello, Puneet Garcha, Gabe Loor, Kenneth Liao, Alexis Shaffi, John Vierling, Rise Stribling, Abbas Rana, John A Goss

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus responsible for a worldwide pandemic has forced drastic changes in medical practice in an alarmingly short period of time. Caregivers must modify their strategies as well as optimize the utilization of resources to ensure public and patient safety. For organ transplantation, in particular, the loss of lifesaving organs for transplantation could lead to increased waitlist mortality. The priority is to select uninfected donors to transplant uninfected recipients while maintaining safety for health care systems in the backdrop of a virulent pandemic. We do not yet have a standard approach to evaluating …