Digital Commons Network^™

Tetraspanin Cd82 Regulates S1pr, Chelsea A. Saito-Reis, Victoria D. Balise, Erica M. Pascetti, Magdalena Jiminez, Jennifer M. Gillette

Pathology Research and Scholarship

Hematopoietic stem and progenitor cell (HSPC) mobilization into the blood occurs under normal physiological conditions and is stimulated in the clinic to enable the isolation of HSPCs for transplantation therapies. In the present study, we identify the tetraspanin CD82 as a novel regulator of HSPC mobilization. Using a global CD82 knockout (CD82KO) mouse, we measure enhanced HSPC mobilization after granulocyte-colony stimulating factor (G-CSF) or AMD3100 treatment, which we find is promoted by increased surface expression of the sphingosine 1-phosphate receptor 1 (S1PR

Long-Term Survival Of Older Patients Hospitalized For Covid-19. Do Clinical Characteristics Upon Admission Matter?, Michał Chojnicki, Agnieszka Neumann-Podczaska, Mikołaj Seostianin, Zofia Tomczak, Hamza Tariq, Jerzy Chudek, Sławomir Tobis, Iwona Mozer-Lisewska, Aleksandra Suwalska, Andrzej Tykarski, Piotr Merks, Sylwia Kropińska, Małgorzata Sobieszczańska, Frank Romanelli, Katarzyna Wieczorowska-Tobis

Pharmacy Practice and Science Faculty Publications

Older adults are particularly susceptible to COVID-19 in terms of both disease severity and risk of death. To compare clinical differences between older COVID-19 hospitalized survivors and non-survivors, we investigated variables influencing mortality in all older adults with COVID-19 hospitalized in Poznań, Poland, through the end of June 2020 (n = 322). In-hospital, post-discharge, and overall 180-day mortality were analyzed. Functional capacity prior to COVID-19 diagnosis was also documented. The mean age of subjects was 77.5 ± 10.0 years; among them, 191 were females. Ninety-five (29.5%) died during their hospitalization and an additional 30 (9.3%) during the post-discharge period …

Project Earthrise: Proceedings Of The Ninth Annual Conference Of Invivo Planetary Health, Susan L. Prescott, Ganesa Wegienka, Remco Kort, David H. Nelson, Sabine Gabrysch, Trevor Hancock, Anita Kozyrskyj, Christopher A. Lowry, Nicole Redvers, Blake Poland, Jake Robinson, Jean-Claude Moubarac, Sara Warber, Janet Jansson, Aki Sinkkonen, John Penders, Susan Erdman, Ralph Nanan, Matilda Van Den Bosch, Kirk Schneider, Nicholas J. Schroeck, Tanja Sobko, Jamie Harvie, George A. Kaplan, Rob Moodie, Laura Lengnick, Isaac Prilleltensky, Yuria Celidwen, Susan H. Berman, Alan C. Logan, Brian Berman

Public Health Sciences Articles

The "Earthrise" photograph, taken on the 1968 Apollo 8 mission, became one of the most significant images of the 20th Century. It triggered a profound shift in environmental awareness and the potential for human unity-inspiring the first Earth Day in 1970. Taking inspiration from these events 50 years later, we initiated

Inhibition Of The Nlrp3 Inflammasome Improves Lifespan In Animal Murine Model Of Hutchinson-Gilford Progeria, Alvaro González-Dominguez, Raúl Montañez, Beatriz Castejón-Vega, Jéssica Nuñez-Vasco, Débora Lendines-Cordero, Chun Wang, Gabriel Mbalaviele, José M Navarro-Pando, Elísabet Alcocer-Gómez, Mario D Cordero

Open Access Publications

Inflammation is a hallmark of aging and accelerated aging syndromes such as Hutchinson-Gilford progeria syndrome (HGPS). In this study, we present evidence of increased expression of the components of the NLRP3 inflammasome pathway in HGPS skin fibroblasts, an outcome that was associated with morphological changes of the nuclei of the cells. Lymphoblasts from HGPS patients also showed increased basal levels of NLRP3 and caspase 1. Consistent with these results, the expression of caspase 1 and Nlrp3, but not of the other inflammasome receptors was higher in the heart and liver of Zmpste24

Rn7sk Small Nuclear Rna Controls Bidirectional Transcription Of Highly Expressed Gene Pairs In Skin, Roberto Bandiera, Rebecca E Wagner, Thiago Britto-Borges, Christoph Dieterich, Sabine Dietmann, Susanne Bornelöv, Michaela Frye

Open Access Publications

Pausing of RNA polymerase II (Pol II) close to promoters is a common regulatory step in RNA synthesis, and is coordinated by a ribonucleoprotein complex scaffolded by the noncoding RNA RN7SK. The function of RN7SK-regulated gene transcription in adult tissue homoeostasis is currently unknown. Here, we deplete RN7SK during mouse and human epidermal stem cell differentiation. Unexpectedly, loss of this small nuclear RNA specifically reduces transcription of numerous cell cycle regulators leading to cell cycle exit and differentiation. Mechanistically, we show that RN7SK is required for efficient transcription of highly expressed gene pairs with bidirectional promoters, which in the epidermis …

Neuron-Specific Imp2 Overexpression By Synapsin Promoter-Driven Aav9: A Tool To Study Its Role In Axon Regeneration., Sarah Blizard, Danielle Park, Natalie O'Toole, Sheeva Norooz, Martin Dela Torre, Young Son, Adam Holstein, Scarlett Austin, Joshua Harman, Samantha Haraszti, Daved Fared, Mei Xu

PCOM Scholarly Works

Insulin-like growth factor II mRNA-binding protein (IMP) 2 is one of the three homologues (IMP1-3) that belong to a conserved family of mRNA-binding proteins. Its alternative splice product is aberrantly expressed in human hepatocellular carcinoma, and it is therefore identified as HCC. Previous works have indicated that IMP1/ZBP1 (zipcode binding protein) is critical in axon guidance and regeneration by regulating localization and translation of specific mRNAs. However, the role of IMP2 in the nervous system is largely unknown. We used the synapsin promoter-driven adeno-associated viral (AAV) 9 constructs for transgene expression both in vitro and in vivo. These viral vectors …

A Guide For Authors And Readers Of The American Society For Nutrition Journals On The Proper Use Of P Values And Strategies That Promote Transparency And Improve Research Reproducibility, John D Sorkin, Mark Manary, Paul A M Smeets, Amanda J Macfarlane, Arne Astrup, Ronald L Prigeon, Beth B Hogans, Jack Odle, Teresa A Davis, Katherine L Tucker, Christopher P Duggan, Deirdre K Tobias

Children’s Nutrition Research Center Staff Publications

Two questions regarding the scientific literature have become grist for public discussion: 1) what place should P values have in reporting the results of studies? 2) How should the perceived difficulty in replicating the results reported in published studies be addressed? We consider these questions to be 2 sides of the same coin; failing to address them can lead to an incomplete or incorrect message being sent to the reader. If P values (which are derived from the estimate of the effect size and a measure of the precision of the estimate of the effect) are used improperly, for example …

Is Executive Dysfunction A Potential Contributor To The Comorbidity Between Basic Reading Disability And Attention-Deficit/Hyperactivity Disorder?, Michelle Y Kibby, Genni Newsham, Zsofia Imre, Jennifer E Schlak

Publications

Our study is one of the few to analyze executive functioning (EF) in a

Functional Reach Test, Single-Leg Stance Test, And Tinetti Performance-Oriented Mobility Assessment For The Prediction Of Falls In Older Adults: A Systematic Review, Humberto Omaña, Kari Bezaire, Kyla Brady, Jayme Davies, Nancy Louwagie, Sean Power, Sydney Santin, Susan W. Hunter

Physical Therapy Publications

OBJECTIVE: The authors sought to systematically review the existing literature on the falls-related diagnostic test properties of the Functional Reach Test (FRT), single-leg stance test (SLST), and Tinetti Performance-Oriented Mobility Assessment (POMA) in older adults across settings and patient populations.

METHODS: The PubMed, EMBASE, and CINAHL databases were searched (inception-July 2020). Inclusion criteria were participants aged 60 years or more, prospectively recorded falls, and the reporting of falls-related predictive validity. Manuscripts not published in English were excluded. Methodological quality of reporting was assessed using the Tooth Scale.

RESULTS: Of 1071 studies reviewed, 21 met the inclusion criteria (12 POMA, 8 …

Initial Laparotomy Versus Peritoneal Drainage In Extremely Low Birthweight Infants With Surgical Necrotizing Enterocolitis Or Isolated Intestinal Perforation: A Multicenter Randomized Clinical Trial, Martin L Blakely, Jon E Tyson, Kevin P Lally, Susan R Hintz, Barry Eggleston, David K Stevenson, Gail E Besner, Abhik Das, Robin K Ohls, William E Truog, Leif D Nelin, Brenda B Poindexter, Claudia Pedroza, Michele C Walsh, Barbara J Stoll, Rachel Geller, Kathleen A Kennedy, Reed A Dimmitt, Waldemar A Carlo, C Michael Cotten, Abbot R Laptook, Krisa P Van Meurs, Kara L Calkins, Gregory M Sokol, Pablo J Sanchez, Myra H Wyckoff, Ravi M Patel, Ivan D Frantz, Seetha Shankaran, Carl T D'Angio, Bradley A Yoder, Edward F Bell, Kristi L Watterberg, Colin A Martin, Carroll M Harmon, Henry Rice, Arlet G Kurkchubasche, Karl Sylvester, James C Y Dunn, Troy A Markel, Diana L Diesen, Amina M Bhatia, Alan Flake, Walter J Chwals, Rebeccah Brown, Kathryn D Bass, Shawn D St Peter, Christina M Shanti, Walter Pegoli, David Skarda, Joel Shilyansky, David G Lemon, Ricardo A Mosquera, Myriam Peralta-Carcelen, Ricki F Goldstein, Betty R Vohr, Isabell B Purdy, Abbey C Hines, Nathalie L Maitre, Roy J Heyne, Sara B Demauro, Elisabeth C Mcgowan, Kimberly Yolton, Howard W Kilbride, Girija Natarajan, Kelley Yost, Sarah Winter, Tarah T Colaizy, Matthew M Laughon, Satyanarayana Lakshminrusimha, Rosemary D Higgins, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Neonatal Research Network

Faculty, Staff and Student Publications

OBJECTIVE: The aim of this study was to determine which initial surgical treatment results in the lowest rate of death or neurodevelopmental impairment (NDI) in premature infants with necrotizing enterocolitis (NEC) or isolated intestinal perforation (IP).

SUMMARY BACKGROUND DATA: The impact of initial laparotomy versus peritoneal drainage for NEC or IP on the rate of death or NDI in extremely low birth weight infants is unknown.

METHODS: We conducted the largest feasible randomized trial in 20 US centers, comparing initial laparotomy versus peritoneal drainage. The primary outcome was a composite of death or NDI at 18 to 22 months corrected …

Initial Laparotomy Versus Peritoneal Drainage In Extremely Low Birthweight Infants With Surgical Necrotizing Enterocolitis Or Isolated Intestinal Perforation: A Multicenter Randomized Clinical Trial, Martin L Blakely, Jon E Tyson, Kevin P Lally, Susan R Hintz, Barry Eggleston, David K Stevenson, Gail E Besner, Abhik Das, Robin K Ohls, William E Truog, Leif D Nelin, Brenda B Poindexter, Claudia Pedroza, Michele C Walsh, Barbara J Stoll, Rachel Geller, Kathleen A Kennedy, Reed A Dimmitt, Waldemar A Carlo, C Michael Cotten, Abbot R Laptook, Krisa P Van Meurs, Kara L Calkins, Gregory M Sokol, Pablo J Sanchez, Myra H Wyckoff, Ravi M Patel, Ivan D Frantz, Seetha Shankaran, Carl T D'Angio, Bradley A Yoder, Edward F Bell, Kristi L Watterberg, Colin A Martin, Carroll M Harmon, Henry Rice, Arlet G Kurkchubasche, Karl Sylvester, James C Y Dunn, Troy A Markel, Diana L Diesen, Amina M Bhatia, Alan Flake, Walter J Chwals, Rebeccah Brown, Kathryn D Bass, Shawn D St Peter, Christina M Shanti, Walter Pegoli, David Skarda, Joel Shilyansky, David G Lemon, Ricardo A Mosquera, Myriam Peralta-Carcelen, Ricki F Goldstein, Betty R Vohr, Isabell B Purdy, Abbey C Hines, Nathalie L Maitre, Roy J Heyne, Sara B Demauro, Elisabeth C Mcgowan, Kimberly Yolton, Howard W Kilbride, Girija Natarajan, Kelley Yost, Sarah Winter, Tarah T Colaizy, Matthew M Laughon, Satyanarayana Lakshminrusimha, Rosemary D Higgins, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Neonatal Research Network

Faculty, Staff and Student Publications

OBJECTIVE: The aim of this study was to determine which initial surgical treatment results in the lowest rate of death or neurodevelopmental impairment (NDI) in premature infants with necrotizing enterocolitis (NEC) or isolated intestinal perforation (IP).

SUMMARY BACKGROUND DATA: The impact of initial laparotomy versus peritoneal drainage for NEC or IP on the rate of death or NDI in extremely low birth weight infants is unknown.

METHODS: We conducted the largest feasible randomized trial in 20 US centers, comparing initial laparotomy versus peritoneal drainage. The primary outcome was a composite of death or NDI at 18 to 22 months corrected …

A Human Ipsc-Derived Inducible Neuronal Model Of Niemann-Pick Disease, Type C1, Anika V Prabhu, Insung Kang, Raffaella De Pace, Christopher A Wassif, Hideji Fujiwara, Pamela Kell, Xuntian Jiang, Daniel S Ory, Juan S Bonifacino, Michael E Ward, Forbes D Porter

2020-Current year OA Pubs

BACKGROUND: Niemann-Pick disease, type C (NPC) is a childhood-onset, lethal, neurodegenerative disorder caused by autosomal recessive mutations in the genes NPC1 or NPC2 and characterized by impaired cholesterol homeostasis, a lipid essential for cellular function. Cellular cholesterol levels are tightly regulated, and mutations in either NPC1 or NPC2 lead to deficient transport and accumulation of unesterified cholesterol in the late endosome/lysosome compartment, and progressive neurodegeneration in affected individuals. Previous cell-based studies to understand the NPC cellular pathophysiology and screen for therapeutic agents have mainly used patient fibroblasts. However, these do not allow modeling the neurodegenerative aspect of NPC disease, highlighting …

Impact Of The Hop-Up-Pt Program On Older Adults At Risk To Fall: A Randomized Controlled Trial, Sara K. Arena, Christopher M. Wilson, Lori Boright, Edward L. Peterson

Public Health Sciences Articles

BACKGROUND: Reduced falls and fall risks have been observed among older adults referred to the HOP-UP-PT (Home-based Older Persons Upstreaming Prevention-Physical Therapy) program. The purpose of this study was to describe outcomes of HOP-UP-PT program participants and then to compare these outcomes to non-participants.

METHODS: Six Michigan senior centers referred adults ≥65 years who were at-risk for functional decline or falls. 144 participants (n = 72 per group) were randomized to either the experimental group (EG) or the control group (CG). Physical therapists (PTs) delivered physical, environmental, and health interventions to the EG over nine encounters (six in-person, three telerehabilitation) …

Development Of Food Pattern Recommendations For Infants And Toddlers 6-24 Months Of Age To Support The Dietary Guidelines For Americans, 2020-2025, Kathryn G Dewey, Tusarebecca Pannucci, Kellie O Casavale, Teresa A Davis, Sharon M Donovan, Ronald E Kleinman, Elsie M Taveras, Regan L Bailey, Rachel Novotny, Barbara O Schneeman, Jamie Stang, Janet De Jesus, Eve E Stoody

Children’s Nutrition Research Center Staff Publications

Background: Developing food-based dietary guidelines (FBDGs) for infants and toddlers is a complex task that few countries have attempted.

Objectives: Our objectives are to describe the process of food pattern modeling (FPM) conducted to develop FBDGs for the Dietary Guidelines for Americans, 2020-2025 for infants 6 to <12 mo and toddlers 12 to <24 mo of age, as well as the implications of the results and areas needing further work.

Methods: The US 2020 Dietary Guidelines Advisory Committee, with the support of federal staff, conducted FPM analyses using 5 steps: 1) identified energy intake targets; 2) established nutritional goals; 3) identified food groupings and expected amounts, using 3 options for the amount of energy from human milk in each age interval; 4) estimated …

Structure Of Venezuelan Equine Encephalitis Virus In Complex With The Ldlrad3 Receptor, Katherine Basore, Hongming Ma, Natasha M Kafai, Samantha Mackin, Arthur S Kim, Christopher A Nelson, Michael S Diamond, Daved H Fremont

Open Access Publications

LDLRAD3 is a recently defined attachment and entry receptor for Venezuelan equine encephalitis virus (VEEV)

Barriers To Human Papillomavirus Vaccine Uptake Among Racial/Ethnic Minorities: A Systematic Review, Trisha L Amboree, Charles Darkoh

Faculty, Staff and Student Publications

BACKGROUND: Human papillomavirus (HPV) is associated with poor health outcomes, including cervical cancer. Racial/ethnic minority populations experience poor health outcomes associated with HPV at higher rates. A vaccine is available to protect against HPV infections and prevent HPV-related sequelae; however, vaccination rates have remained low in the United States (U.S.) population. Thus, there is an urgent need to increase the HPV vaccination rate. Moreover, little is known about barriers to HPV vaccination in racial/ethnic minority groups. This paper highlights the most recent findings on barriers experienced by these groups.

METHODS: The PubMed database was searched on July 30, 2020, for …

Flowcharts Improve Periodontal Diagnosis By Dental And Dental Hygiene Students, Karo Parsegian, Srinivas Ayilavarapu, Tulsi Patel, Harold A Henson, Nikola Angelov

Faculty, Staff and Student Publications

BACKGROUND: In 2017, the American Academy of Periodontology and the European Federation of Periodontology updated the classification of periodontal and peri-implant diseases and conditions. The goal of the present crossover study was to develop straightforward, illustrative flowcharts and determine their impact on the accuracy and speed of diagnosing periodontal conditions by predoctoral dental students (DS) and dental hygiene students (DHS).

METHODS: Two flowcharts (a decision-tree flowchart and one based on the periodontal disease/condition entity) were developed using updated diagnostic determinants proposed by the 2017 classification. A total of 26 second-, third-, and fourth-year DS (DS2, DS3, and DS4, respectively) and …

Posttraumatic Stress Symptom Clusters Differentially Predict Late Positive Potential To Cocaine Imagery Cues In Trauma-Exposed Adults With Cocaine Use Disorder, Heather E Webber, Danielle A Kessler, Emma C Lathan, Margaret C Wardle, Charles E Green, Joy M Schmitz, Scott D Lane, Anka A Vujanovic

Faculty, Staff and Student Publications

BACKGROUND: While studies have investigated the effects of posttraumatic stress disorder (PTSD) symptoms on substance use, information on these associations in the context of drug cue reactivity is lacking, which can provide meaningful information about risk for relapse. The current study assessed the associations between PTSD symptom clusters and reactivity to cues in trauma-exposed adults with cocaine use disorder.

METHODS: We recorded electroencephalogram on 52 trauma-exposed participants (M

RESULTS: Linear mixed modeling indicated that higher NACM symptomatology was associated with higher LPPs to cocaine cues and higher arousal/reactivity was associated with lower LPPs to cocaine cues.

CONCLUSIONS: These results highlight …

Protocol For Draup: A Deimplementation Programme To Decrease Routine Chest Radiographs After Central Venous Catheter Insertion, Enyo Ablordeppey, Byron Powell, Virginia Mckay, Shannon Keating, Aimee James, Christopher Carpenter, Marin Kollef, Richard Griffey

Open Access Publications

INTRODUCTION: Avoiding low value medical practices is an important focus in current healthcare utilisation. Despite advantages of point-of-care ultrasound (POCUS) over chest X-ray including improved workflow and timeliness of results, POCUS-guided central venous catheter (CVC) position confirmation has slow rate of adoption. This demonstrates a gap that is ripe for the development of an intervention.

METHODS: The intervention is a deimplementation programme called DRAUP (

ETHICS AND DISSEMINATION: Approval of the study by the Human Research Protection Office has been obtained. This work will be disseminated by publication of peer-reviewed manuscripts, presentation in abstract form at scientific meetings and data …

Rare Variants In Kdr, Encoding Vegf Receptor 2, Are Associated With Tetralogy Of Fallot., Doris Škorić-Milosavljević, Najim Lahrouchi, Fernanda M. Bosada, Gregor Dombrowsky, Simon G. Williams, Robert Lesurf, Fleur V Y Tjong, Roddy Walsh, Ihssane El Bouchikhi, Jeroen Breckpot, Enrique Audain, Aho Ilgun, Leander Beekman, Ilham Ratbi, Alanna Strong, Maximilian Muenke, Solveig Heide, Alison M. Muir, Mariam Hababa, Laura A. Cross, Dihong Zhou, T Pastinen, German Competence Network For Congenital Heart Defects, Elaine Zackai, Samir Atmani, Karim Ouldim, Najlae Adadi, Katharina Steindl, Anita Rauch, David Brook, Anna Wilsdon, Irene Kuipers, Nico A. Blom, Barbara J. Mulder, Heather C. Mefford, Boris Keren, Pascal Joset, Paul Kruszka, Isabelle Thiffault, Sarah E. Sheppard, Amy Roberts, Elisabeth M. Lodder, Bernard D. Keavney, Sally-Ann B. Clur, Seema Mital, Marc-Philip Hitz, Vincent M. Christoffels, Alex V. Postma, Connie R. Bezzina

Manuscripts, Articles, Book Chapters and Other Papers

Purpose: Rare genetic variants in KDR, encoding the vascular endothelial growth factor receptor 2 (VEGFR2), have been reported in patients with tetralogy of Fallot (TOF). However, their role in disease causality and pathogenesis remains unclear.

Methods: We conducted exome sequencing in a familial case of TOF and large-scale genetic studies, including burden testing, in >1,500 patients with TOF. We studied gene-targeted mice and conducted cell-based assays to explore the role of KDR genetic variation in the etiology of TOF.

Results: Exome sequencing in a family with two siblings affected by TOF revealed biallelic missense variants in KDR. Studies in knock-in …

Growth Rates Of Infants Randomized To Continuous Positive Airway Pressure Or Intubation After Extremely Preterm Birth, Ariel A. Salas, Waldemar A. Carlo, Barbara T. Do, Edward F. Bell, Abhik Das, Krisa P. Van Meurs, Brenda B. Poindexter, Seetha Shankaran, Noelle Younge, Kristi L. Watterberg, Rosemary D. Higgins, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Neonatal Research Network

Pediatrics Research and Scholarship

OBJECTIVE: To evaluate the effects of early treatment with continuous positive airway pressure (CPAP) on nutritional intake and in-hospital growth rates of extremely preterm (EPT) infants.

STUDY DESIGN: EPT infants (24

RESULTS: Growth data were analyzed for 810 of 1316 infants enrolled in SUPPORT (414 in the intervention group, 396 in the control group). The median gestational age was 26 weeks, and the mean birth weight was 839 g. Baseline characteristics, total nutritional intake, and in-hospital comorbidities were not significantly different between the 2 groups. In a regression model, growth rates between birth and 36 weeks of PMA, as well …

Ethics Of Ai In Pathology: Current Paradigms And Emerging Issues, Chhavi Chauhan, Rama R. Gullapalli

Pathology Research and Scholarship

Deep learning has rapidly advanced artificial intelligence (AI) and algorithmic decision-making (ADM) paradigms, affecting many traditional fields of medicine, including pathology, which is a heavily data-centric specialty of medicine. The structured nature of pathology data repositories makes it highly attractive to AI researchers to train deep learning models to improve health care delivery. Additionally, there are enormous financial incentives driving adoption of AI and ADM due to promise of increased efficiency of the health care delivery process. AI, if used unethically, may exacerbate existing inequities of health care, especially if not implemented correctly. There is an urgent need to harness …

Clinical Trial And Postmarketing Safety Of Onasemnogene Abeparvovec Therapy, John W Day, Jerry R Mendell, Eugenio Mercuri, Richard S Finkel, Kevin A Strauss, Aaron Kleyn, Sitra Tauscher-Wisniewski, Francis Fonyuy Tukov, Sandra P Reyna, Deepa H Chand

2020-Current year OA Pubs

INTRODUCTION: This is the first description of safety data for intravenous onasemnogene abeparvovec, the only approved systemically administered gene-replacement therapy for spinal muscular atrophy.

OBJECTIVE: We comprehensively assessed the safety of intravenous onasemnogene abeparvovec from preclinical studies, clinical studies, and postmarketing data.

METHODS: Single-dose toxicity studies were performed in neonatal mice and juvenile or neonatal cynomolgus nonhuman primates (NHPs). Data presented are from a composite of preclinical studies, seven clinical trials, and postmarketing sources (clinical trials, n = 102 patients; postmarketing surveillance, n = 665 reported adverse event [AE] cases). In clinical trials, safety was assessed through AE monitoring, vital-sign …

Advances In Optical Gastrointestinal Endoscopy: A Technical Review, Yubo Tang, Sharmila Anandasabapathy, Rebecca Richards-Kortum

Faculty, Staff and Students Publications

Optical endoscopy is the primary diagnostic and therapeutic tool for management of gastrointestinal (GI) malignancies. Most GI neoplasms arise from precancerous lesions; thus, technical innovations to improve detection and diagnosis of precancerous lesions and early cancers play a pivotal role in improving outcomes. Over the last few decades, the field of GI endoscopy has witnessed enormous and focused efforts to develop and translate accurate, user-friendly, and minimally invasive optical imaging modalities. From a technical point of view, a wide range of novel optical techniques is now available to probe different aspects of light-tissue interaction at macroscopic and microscopic scales, complementing …

Pancreatic Differentiation Of Stem Cells Reveals Pathogenesis Of A Syndrome Of Ketosis-Prone Diabetes, Diane Yang, Sanjeet Patel, Wojciech J Szlachcic, Jolanta Chmielowiec, Diane Scaduto, Nagireddy Putluri, Arun Sreekumar, James Suliburk, Michael Metzker, Ashok Balasubramanyam, Malgorzata Borowiak

Faculty, Staff and Students Publications

Genetic analysis of an adult patient with an unusual course of ketosis-prone diabetes (KPD) and lacking islet autoantibodies demonstrated a nucleotide variant in the 5′-untranslated region (UTR) of PDX1, a β-cell development gene. When differentiated to the pancreatic lineage, his induced pluripotent stem cells stalled at the definitive endoderm (DE) stage. Metabolomics analysis of the cells revealed that this was associated with leucine hypersensitivity during transition from the DE to the pancreatic progenitor (PP) stage, and RNA sequencing showed that defects in leucine-sensitive mTOR pathways contribute to the differentiation deficiency. CRISPR/Cas9 manipulation of the PDX1 variant demonstrated that it …

Looking For Consistency In An Uncertain World: Test-Retest Reliability Of Neurophysiological And Behavioral Readouts In Autism., Shlomit Beker, John J Foxe, John Venticinque, Juliana Bates, Elizabeth M Ridgeway, Roseann C Schaaf, Sophie Molholm

Department of Occupational Therapy Faculty Papers

BACKGROUND: Autism spectrum disorders (ASD) are associated with altered sensory processing and perception. Scalp recordings of electrical brain activity time-locked to sensory events (event-related potentials; ERPs) provide precise information on the time-course of related altered neural activity, and can be used to model the cortical loci of the underlying neural networks. Establishing the test-retest reliability of these sensory brain responses in ASD is critical to their use as biomarkers of neural dysfunction in this population.

METHODS: EEG and behavioral data were acquired from 33 children diagnosed with ASD aged 6-9.4 years old, while they performed a child-friendly task at two …

Fast Generation Of Lung Sbrt Plans With A Knowledge-Based Planning Model On Ring-Mounted Halcyon Linac, Justin Visak, Aaron Webster, Mark E. Bernard, Mahesh R. Kudrimoti, Marcus E. Randall, Ronald C. Mcgarry, Damodar Pokhrel

Radiation Medicine Faculty Publications

PURPOSE: To demonstrate fast treatment planning feasibility of stereotactic body radiation therapy (SBRT) for centrally located lung tumors on Halcyon Linac via a previously validated knowledge-based planning (KBP) model to support offline adaptive radiotherapy.

MATERIALS/METHODS: Twenty previously treated non-coplanar volumetric-modulated arc therapy (VMAT) lung SBRT plans (c-Truebeam) on SBRT-dedicated C-arm Truebeam Linac were selected. Patients received 50 Gy in five fractions. c-Truebeam plans were re-optimized for Halcyon manually (m-Halcyon) and with KBP model (k-Halcyon). Both m-Halcyon and k-Halcyon plans were normalized for identical or better target coverage than clinical c-Truebeam …

Rapidiron: Reducing Anaemia In Pregnancy In India-A 3-Arm, Randomized-Controlled Trial Comparing The Effectiveness Of Oral Iron With Single-Dose Intravenous Iron In The Treatment Of Iron Deficiency Anaemia In Pregnant Women And Reducing Low Birth Weight Deliveries., Richard J. Derman, Shivaprasad S. Goudar, Simal Thind, Sudhir Bhandari, Zubair H. Aghai, Michael Auerbach, Rupsa Boelig, Umesh S. Charantimath, Rosemary Frasso, M. S. Ganachari, Kusum Lata Gaur, Michael K. Georgieff, Frances Jaeger, S. Yogeshkumar, Parth Lalakia, Benjamin Leiby, Mita Majumdar, Amarjeet Mehta, Seema Mehta, Sudhir Mehta, Stephen T. Mennemeyer, Amit P. Revankar, Dharmesh Kumar Sharma, Vanessa Short, Manjunath S Somannavar, Dennis Wallace, Hemang Shah, Manjula Singh, Sufia Askari, Mrutyunjaya B. Bellad, Rapidiron Trial Group

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Anaemia is a worldwide problem and iron deficiency is the most common cause. In pregnancy, anaemia increases the risk of adverse maternal, foetal and neonatal outcomes. India's anaemia rate is among the highest in the world with India's National Family Health Survey indicating over 50% of pregnant women were affected by anaemia. India's Anaemia Mukt Bharat-Intensified National Iron Plus Initiative aims to reduce the prevalence of anaemia among reproductive-age women, adolescents and children by 3% per year and facilitate the achievement of a Global World Health Assembly 2025 objective to achieve a 50% reduction of anaemia among women of …

Validation Of An Electronic Trigger To Measure Missed Diagnosis Of Stroke In Emergency Departments, Viralkumar Vaghani, Li Wei, Umair Mushtaq, Dean F Sittig, Andrea Bradford, Hardeep Singh

Faculty, Staff and Students Publications

OBJECTIVE: Diagnostic errors are major contributors to preventable patient harm. We validated the use of an electronic health record (EHR)-based trigger (e-trigger) to measure missed opportunities in stroke diagnosis in emergency departments (EDs).

METHODS: Using two frameworks, the Safer Dx Trigger Tools Framework and the Symptom-disease Pair Analysis of Diagnostic Error Framework, we applied a symptom-disease pair-based e-trigger to identify patients hospitalized for stroke who, in the preceding 30 days, were discharged from the ED with benign headache or dizziness diagnoses. The algorithm was applied to Veteran Affairs National Corporate Data Warehouse on patients seen between 1/1/2016 and 12/31/2017. Trained …

Current Neurologic Treatment And Emerging Therapies In Cdkl5 Deficiency Disorder, Heather E Olson, Judith L Weisenberg, Et Al.

2020-Current year OA Pubs

BACKGROUND: CDKL5 deficiency disorder (CDD) is associated with refractory infantile onset epilepsy, global developmental delay, and variable features that include sleep, behavioral disturbances, and movement disorders. Current treatment is primarily symptom-based and informed by experience in caring for this population.

METHODS: We describe medication and non-medication approaches to treatment of epilepsy and additional key neurologic symptoms (sleep disturbances, behavioral issues, movement disorders, and swallowing dysfunction) in a cohort of 177 individuals meeting criteria for CDD, 154 evaluated at 4 CDKL5 Centers of Excellence in the USA and 40 identified through the NIH Natural History Study of Rett and Related Disorders. …