Digital Commons Network^™

Untargeted Metabolomic Analysis Of Human Milk From Mothers Of Preterm Infants, Lila S Nolan, Angela N Lewis, Qingqing Gong, James J Sollome, Olivia N Dewitt, Robert D Williams, Misty Good

2020-Current year OA Pubs

The application of metabolomics in neonatology offers an approach to investigate the complex relationship between nutrition and infant health. Characterization of the metabolome of human milk enables an investigation into nutrients that affect the neonatal metabolism and identification of dietary interventions for infants at risk of diseases such as necrotizing enterocolitis (NEC). In this study, we aimed to identify differences in the metabolome of breast milk of 48 mothers with preterm infants with NEC and non-NEC healthy controls. A minimum significant difference was observed in the human milk metabolome between the mothers of infants with NEC and mothers of healthy …

Cullin4 E3 Ubiquitin Ligases Regulate Male Gonocyte Migration, Proliferation And Blood-Testis Barrier Homeostasis, Yan Yin, Liming Zhu, Qiufang Li, Pengbo Zhou, Liang Ma

Open Access Publications

Ubiquitination, an essential posttranslational modification, plays fundamental roles during mammalian spermatogenesis. We previously reported the requirement of two Cullin 4 ubiquitin ligase family genes, Cullin 4a (

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 …

Derivation And External Validation Of A Simple Risk Score To Predict In-Hospital Mortality In Patients Hospitalized For Covid-19: A Multicenter Retrospective Cohort Study, Charlotte Z. Mann, Chelsea Abshire, Monica Yost, Scott Kaatz, Lakshmi Swaminathan, Scott A. Flanders, Hallie C. Prescott, Johann A. Gagnon-Bartsch

Hospital Medicine Articles

ABSTRACT: As severe acute respiratory syndrome coronavirus 2 continues to spread, easy-to-use risk models that predict hospital mortality can assist in clinical decision making and triage. We aimed to develop a risk score model for in-hospital mortality in patients hospitalized with 2019 novel coronavirus (COVID-19) that was robust across hospitals and used clinical factors that are readily available and measured standardly across hospitals. In this retrospective observational study, we developed a risk score model using data collected by trained abstractors for patients in 20 diverse hospitals across the state of Michigan (Mi-COVID19) who were discharged between March 5, 2020 and …

Patient-Reported Reasons For Stopping Care Or Switching Clinics In Zambia: A Multisite, Regionally Representative Estimate Using A Multistage Sampling-Based Approach In Zambia, Izukanji Sikazwe, Ingrid Eshun-Wilson, Kombatende Sikombe, Laura K Beres, Paul Somwe, Aaloke Mody, Sandra Simbeza, Chama Bukankala, David V Glidden, Lloyd B Mulenga, Nancy Padian, Peter Ehrenkranz, Carolyn Bolton-Moore, Charles B Holmes, Elvin H Geng

2020-Current year OA Pubs

BACKGROUND: Understanding patient-reported reasons for lapses of retention in human immunodeficiency virus (HIV) treatment can drive improvements in the care cascade. A systematic assessment of outcomes among a random sample of patients lost to follow-up (LTFU) from 32 clinics in Zambia to understand the reasons for silent transfers and disengagement from care was undertaken.

METHODS: We traced a simple random sample of LTFU patients (>90 days from last scheduled visit) as determined from clinic-based electronic medical records from a probability sample of facilities. Among patients found in person, we solicited reasons for either stopping or switching care and predictors …

Heterogeneity Of Magnitude, Allergen Immunodominance, And Cytokine Polarization Of Cockroach Allergen-Specific T Cell Responses In Allergic Sensitized Children., Ricardo Da Silva Antunes, Aaron Sutherland, April Frazier, Veronique Schulten, Anna Pomés, Jill Glesner, Agustin Calatroni, Matthew C Altman, Robert A Wood, George T O'Connor, Jacqueline A Pongracic, Gurjit K Khurana Hershey, Carolyn M Kercsmar, Rebecca S Gruchalla, Michelle Gill, Andrew H Liu, Edward Zoratti, Meyer Kattan, Paula J Busse, Leonard B Bacharier, Stephen J. Teach, Lisa M Wheatley, Alkis Togias, William W Busse, Daniel J Jackson, Alessandro Sette

Pediatrics Faculty Publications

Background: Characterization of allergic responses to cockroach (CR), a common aeroallergen associated with asthma, has focused mainly on IgE reactivity, but little is known about T cell responses, particularly in children. We conducted a functional evaluation of CR allergen-specific T cell reactivity in a cohort of CR allergic children with asthma.

Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 71 children, with mild-to-moderate asthma who were enrolled in a CR immunotherapy (IT) clinical trial, prior to treatment initiation. PBMC were stimulated with peptide pools derived from 11 CR allergens, and CD4+ T cell responses assessed by intracellular cytokine staining. …

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 …

Co-Contraction Of Ankle Muscle Activity During Quiet Standing In Individuals With Incomplete Spinal Cord Injury Is Associated With Postural Instability, Kai Lon Fok, Jae W Lee, Janelle Unger, Katherine Chan, Kristin E Musselman, Kei Masani

Physical Therapy Publications

Previous findings indicate that co-contractions of plantarflexors and dorsiflexors during quiet standing increase the ankle mechanical joint stiffness, resulting in increased postural sway. Balance impairments in individuals with incomplete spinal cord injury (iSCI) may be due to co-contractions like in other individuals with reduced balance ability. Here we investigated the effect of co-contraction between plantar- and dorsiflexors on postural balance in individuals with iSCI (iSCI-group) and able-bodied individuals (AB-group). Thirteen able-bodied individuals and 13 individuals with iSCI were asked to perform quiet standing with their eyes open (EO) and eyes closed (EC). Kinetics and electromyograms from the tibialis anterior (TA), …

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 …

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 …

Evaluation Of Population-Level Changes Associated With The 2021 Us Preventive Services Task Force Lung Cancer Screening Recommendations In Community-Based Health Care Systems, Debra P. Ritzwoller, Rafael Meza, Nikki M. Carroll, Erica Blum-Barnett, Andrea N. Burnett-Hartman, Robert T. Greenlee, Stacey A. Honda, Christine Neslund-Dudas, Katharine A. Rendle, Anil Vachani

Public Health Sciences Articles

Importance: The US Preventive Services Task Force (USPSTF) released updated lung cancer screening recommendations in 2021, lowering the screening age from 55 to 50 years and smoking history from 30 to 20 pack-years. These changes are expected to expand screening access to women and racial and ethnic minority groups.

Objective: To estimate the population-level changes associated with the 2021 USPSTF expansion of lung cancer screening eligibility by sex, race and ethnicity, sociodemographic factors, and comorbidities in 5 community-based health care systems.

Design, Setting, and Participants: This cohort study analyzed data of patients who received care from any of 5 community-based …

Hematopoietic Cell Transplantation Cures Adenosine Deaminase 2 Deficiency: Report On 30 Patients, Hasan Hashem, Giorgia Bucciol, Seza Ozen, Sule Unal, Ikbal Ok Bozkaya, Nurten Akarsu, Mervi Taskinen, Minna Koskenvuo, Janna Saarela, Dimana Dimitrova, Dennis D. Hickstein, Amy P. Hsu, Steven M. Holland, Robert Krance, Ghadir Sasa, Ashish R. Kumar, Ingo Müller, Monica Abreu De Sousa, Selket Delafontaine, Leen Moens, Florian Babor, Federica Barzaghi, Maria Pia Cicalese, Robbert Bredius, Joris Van Montfrans, Valentina Baretta, Simone Cesaro, Polina Stepensky, Neven Benedicte, Despina Moshous, Guillaume Le Guenno, David Boutboul, Jignesh Dalal, Joel P. Brooks, Elif Dokmeci, Jasmeen Dara, Carrie L. Lucas, Sophie Hambleton, Keith Wilson, Stephen Jolles, Yener Koc, Tayfun Güngör, Caroline Schnider, Fabio Candotti, Sandra Steinmann, Ansgar Schulz, Chip Chambers, Michael Hershfield, Amanda Ombrello, Jennifer A. Kanakry, Isabelle Meyts

Pediatrics Research and Scholarship

PURPOSE: Deficiency of adenosine deaminase 2 (DADA2) is an inherited inborn error of immunity, characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency, lymphoproliferation, immune cytopenias, and bone marrow failure (BMF). Tumor necrosis factor (TNF-α) blockade is the treatment of choice for the vasculopathy, but often fails to reverse refractory cytopenia. We aimed to study the outcome of hematopoietic cell transplantation (HCT) in patients with DADA2.

METHODS: We conducted a retrospective study on the outcome of HCT in patients with DADA2. The primary outcome was overall survival (OS).

RESULTS: Thirty DADA2 patients …

Activation Of The Innate Immune System In Children With Irritable Bowel Syndrome Evidenced By Increased Fecal Human Β-Defensin-2, Robert J Shulman, Sridevi Devaraj, Margaret Heitkemper

Children’s Nutrition Research Center Staff Publications

Background & aims: The role of the innate immune system in functional gastrointestinal pain disorders is unclear. We investigated the role of β-defensin-2 and gut permeability in childhood irritable bowel syndrome (IBS) and functional abdominal pain (FAP) symptom generation.

Methods: Fecal β-defensin-2 (and in a subset, gut permeability) was measured in children with IBS (n = 116), FAP (n = 33), and healthy control (HC) children (n = 72). IBS and FAP patients were recruited from tertiary and primary care, and HCs were recruited from primary care.

Results: β-defensin-2 concentration was greater in children with IBS (P = .003) 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 …

Safety, Pharmacokinetics And Antiviral Activity Of Pgt121, A Broadly Neutralizing Monoclonal Antibody Against Hiv-1: A Randomized, Placebo-Controlled, Phase 1 Clinical Trial, Kathryn E Stephenson, Boris Julg, C Sabrina Tan, Rebecca Zash, Stephen R Walsh, Charlotte-Paige Rolle, Ana N Monczor, Sofia Lupo, Huub C Gelderblom, Jessica L Ansel, Diane G Kanjilal, Lori F Maxfield, Joseph Nkolola, Erica N Borducchi, Peter Abbink, Jinyan Liu, Lauren Peter, Abishek Chandrashekar, Ramya Nityanandam, Zijin Lin, Alessandra Setaro, Joseph Sapiente, Zhilin Chen, Lisa Sunner, Tyler Cassidy, Chelsey Bennett, Alicia Sato, Bryan Mayer, Alan S Perelson, Allan Decamp, Frances H Priddy, Kshitij Wagh, Elena E Giorgi, Nicole L Yates, Roberto C Arduino, Edwin Dejesus, Georgia D Tomaras, Michael S Seaman, Bette Korber, Dan H Barouch

Faculty, Staff and Student Publications

Human immunodeficiency virus (HIV)-1-specific broadly neutralizing monoclonal antibodies are currently under development to treat and prevent HIV-1 infection. We performed a single-center, randomized, double-blind, dose-escalation, placebo-controlled trial of a single administration of the HIV-1 V3-glycan-specific antibody PGT121 at 3, 10 and 30 mg kg

Assessing Procedural Pain In Infants: A Feasibility Study Evaluating A Point-Of-Care Mobile Solution Based On Automated Facial Analysis, Kreshnik Hoti, Paola Teresa Chivers, Jeffery David Hughes

Research outputs 2014 to 2021

BACKGROUND: The management of procedural pain in infants is suboptimal, in part, compounded by the scarcity of a simple, accurate, and reliable method of assessing such pain. In this study, we aimed to evaluate the psychometric properties of the PainChek Infant, a point-of-care mobile application that uses automated facial evaluation and analysis in the assessment of procedural pain in infants. METHODS: Video recordings of 40 infants were randomly chosen from a purposely assembled digital library of 410 children undergoing immunisation as part of their standard care in Prishtina, Kosovo, between April 4, 2017, and July 11, 2018. For each infant …

Ct Findings And Patterns Of E-Cigarette Or Vaping Product Use-Associated Lung Injury: A Multicenter Cohort Of 160 Cases, Seth J Kligerman, Constantine A Raptis, Kaitlin M Marquis, Et Al.

2020-Current year OA Pubs

BACKGROUND: e-Cigarette or vaping-induced lung injury (EVALI) causes a spectrum of CT lung injury patterns. Relative frequencies and associations with vaping behavior are unknown.

RESEARCH QUESTION: What are the frequencies of imaging findings and CT patterns in EVALI and what is the relationship to vaping behavior?

STUDY DESIGN AND METHODS: CT scans of 160 subjects with EVALI from 15 institutions were retrospectively reviewed. CT findings and patterns were defined and agreed on via consensus. The parenchymal organizing pneumonia (OP) pattern was defined as regional or diffuse ground-glass opacity (GGO) ± consolidation without centrilobular nodules (CNs). An airway-centered OP pattern was …

Prevention And Screening Of Hpv Malignancies, Kristina R Dahlstrom, Andrew T Day, Erich M Sturgis

Faculty, Staff and Students Publications

It is estimated that 5% of the global cancer burden, or approximately 690,000 cancer cases annually, is attributable to human papillomavirus (HPV). Primary prevention through prophylactic vaccination is the best option for reducing the burden of HPV-related cancers. Most high-income countries (HICs) have introduced the HPV vaccine and are routinely vaccinating adolescent boys and girls. Unfortunately, although they suffer the greatest morbidity and mortality due to HPV-related cancers, many lower- and middle-income countries (LMICs) have been unable to initiate and sustain vaccination programs. Secondary prevention in the form of screening has led to substantial declines in cervical cancer incidence in …

Adjuvant Platinum-Based Chemotherapy In Radically Resected Adrenocortical Carcinoma: A Cohort Study, Otilia Kimpel, Sara Bedrose, Felix Megerle, Alfredo Berruti, Massimo Terzolo, Matthias Kroiss, Knut Mai, Olaf M Dekkers, Mouhammed Amir Habra, Martin Fassnacht

Faculty, Staff and Students Publications

BACKGROUND: After radical resection, patients with adrenocortical carcinoma (ACC) frequently experience recurrence and, therefore, effective adjuvant treatment is urgently needed. The aim of the study was to investigate the role of adjuvant platinum-based therapy.

METHODS: In this retrospective multicentre cohort study, we identified patients treated with adjuvant platinum-based chemotherapy after radical resection and compared them with patients without adjuvant chemotherapy. Recurrence-free and overall survival (RFS/OS) were investigated in a matched group analysis and by applying a propensity score matching using the full control cohort (n = 268). For both approaches, we accounted for immortal time bias.

RESULTS: Of the 31 …

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 …

White Matter Plasticity In Healthy Older Adults: The Effects Of Aerobic Exercise, Andrea Mendez Colmenares, Michelle W Voss, Jason Fanning, Elizabeth A Salerno, Neha P Gothe, Michael L Thomas, Edward Mcauley, Arthur F Kramer, Agnieszka Z Burzynska

2020-Current year OA Pubs

White matter deterioration is associated with cognitive impairment in healthy aging and Alzheimer's disease. It is critical to identify interventions that can slow down white matter deterioration. So far, clinical trials have failed to demonstrate the benefits of aerobic exercise on the adult white matter using diffusion Magnetic Resonance Imaging. Here, we report the effects of a 6-month aerobic walking and dance interventions (clinical trial NCT01472744) on white matter integrity in healthy older adults (n = 180, 60-79 years) measured by changes in the ratio of calibrated T1- to T2-weighted images (T1w/T2w). Specifically, the aerobic walking and social dance interventions …

Multicenter, Double-Blind, Placebo-Controlled Trial Of Seviprotimut-L Polyvalent Melanoma Vaccine In Patients With Post-Resection Melanoma At High Risk Of Recurrence, Craig L Slingluff, Leonel Hernandez-Aya, Et Al

2020-Current year OA Pubs

BACKGROUND: Most patients with advanced melanomas relapse after checkpoint blockade therapy. Thus, immunotherapies are needed that can be applied safely early, in the adjuvant setting. Seviprotimut-L is a vaccine containing human melanoma antigens, plus alum. To assess the efficacy of seviprotimut-L, the Melanoma Antigen Vaccine Immunotherapy Study (MAVIS) was initiated as a three-part multicenter, double-blind, placebo-controlled phase III trial. Results from part B1 are reported here.

METHODS: Patients with AJCC V.7 stage IIB-III cutaneous melanoma after resection were randomized 2:1, with stage stratification (IIB/C, IIIA, IIIB/C), to seviprotimut-L 40 mcg or placebo. Recurrence-free survival (RFS) was the primary endpoint. For …

Management And Outcomes Of Cardiogenic Shock In Cardiac Icus With Versus Without Shock Teams., Alexander I Papolos, Benjamin B Kenigsberg, David D Berg, Carlos L Alviar, Erin Bohula, James A Burke Md, Anthony P Carnicelli, Sunit-Preet Chaudhry, Stavros Drakos, Daniel A Gerber, Jianping Guo, James M Horowitz, Jason N Katz, Ellen C Keeley, Thomas S Metkus, Jose Nativi-Nicolau, Jeffrey R Snell, Shashank S Sinha, Wayne J Tymchak, Sean Van Diepen, David A Morrow, Christopher F Barnett

Cardiology Division

BACKGROUND: Single-center studies suggest that implementation of multidisciplinary cardiogenic shock (CS) teams is associated with improved CS survival.

OBJECTIVES: The aim was to characterize practice patterns and outcomes in the management of CS across multiple centers with versus without shock teams.

METHODS: The Critical Care Cardiology Trials Network is a multicenter network of cardiac intensive care units (CICUs) in North America. All consecutive medical admissions to each CICU (n = 24) were captured during annual 2-month collection periods (2017-2019; n = 6,872). Shock management and CICU mortality among centers with versus without shock teams were compared using inverse probability weighting. …

A Novel Mitragynine Analog With Low-Efficacy Mu Opioid Receptor Agonism Displays Antinociception With Attenuated Adverse Effects, Soumen Chakraborty, Abdelfattah Faouzi, Sarah M Bernhard, Nitin Nuthikattu, Rahul Jilakara, Satyanarayana M Chintala, Tao Che, Susruta Majumdar, Et Al

2020-Current year OA Pubs

Mitragynine and 7-hydroxymitragynine (7OH) are the major alkaloids mediating the biological actions of the psychoactive plant kratom. To investigate the structure-activity relationships of mitragynine/7OH templates, we diversified the aromatic ring of the indole at the C9, C10, and C12 positions and investigated their G-protein and arrestin signaling mediated by mu opioid receptors (MOR). Three synthesized lead C9 analogs replacing the 9-OCH

Exploring Contextual Factors Influencing The Implementation Of Evidence-Based Care For Hypertension In Rwanda: A Cross-Sectional Study Using The Coach Questionnaire, Ana Baumann, Cole Hooley, Charles Goss, Vincent Mutabazi, Angela Brown, Kenneth Schechtman, Marc Twagirumukiza, Lisa De Las Fuentes, Dominic Reeds, Makeda Williams, Eugene Mutimura, Anna Bergström, Aurore Nishimwe, Cecile Ingabire, Victor Davila-Roman

Open Access Publications

IMPORTANCE: Hypertension is the largest contributor to the Global Burden of Disease. In Rwanda, as in most low-income and middle-income countries, an increasing prevalence of hypertension and its associated morbidity and mortality is causing major healthcare and economic impact. Understanding healthcare systems context in hypertension care is necessary.

OBJECTIVE: To study the hypertension healthcare context as perceived by healthcare providers using the Context Assessment for Community Health (COACH) tool.

DESIGN: A cross-sectional cohort responded to the COACH questionnaire and a survey about hypertension training.

SETTING: Three tertiary care hospitals in Rwanda.

PARTICIPANTS: Healthcare professionals (n=223).

PRIMARY OUTCOMES AND MEASURES: The …

Trichomonas Vaginalis Detection In Urogenital Specimens From Symptomatic And Asymptomatic Men And Women By Use Of The Cobas Tv/Mg Test, Barbara Van Der Pol, David Eisenberg, Et Al

Open Access Publications

Trichomonas vaginalis is a prevalent sexually transmitted infection (STI). Diagnosis has historically relied on either microscopic analysis or culture, the latter being the previous gold standard. However, these tests are not readily available for male diagnosis, generally only perform well for symptomatic women, and are not as sensitive as nucleic acid amplification tests (NAATs). Men are largely asymptomatic but carry the organism and transmit to their sexual partners. This multicenter, prospective study evaluated the performance of the cobas T. vaginalis/Mycoplasma genitalium (TV/MG) assay for detection of T. vaginalis DNA compared with patient infection status (PIS) defined by a combination of …

Determining Effective Drug Concentrations For Selection And Counterselection Genetics In Drosophila Melanogaster, Nick Matinyan, Yezabel Gonzalez, Herman A Dierick, Koen J T Venken

Faculty, Staff and Students Publications

We recently integrated into fly genetics a set of four selection and two counterselection markers and their corresponding drugs that can be used individually or in combination. These markers eliminate the need to visually screen progeny. Before using these markers in new genetic backgrounds, effective selection/counterselection concentrations should be established for each marker/drug combination. This protocol describes how to set up, perform, and analyze a drug titration curve to determine the effective selection/counterselection drug concentrations for their corresponding markers. For complete details on the use and execution of this protocol, please refer to Matinyan et al., 2021.

Molecular Classification Improves Risk Assessment In Adult Bcr-Abl1-Negative B-All, Elisabeth Paietta, Kathryn G. Roberts, Victoria Wang, Zhaohui Gu, Georgina A N Buck, Deqing Pei, Cheng Cheng, Ross L. Levine, Omar Abdel-Wahab, Zhongshan Cheng, Gang Wu, Chunxu Qu, Lei Shi, Stanley Pounds, Cheryl L. Willman, Richard Harvey, Janis Racevskis, Jan Barinka, Yanming Zhang, Gordon W. Dewald, Rhett P. Ketterling, David Alejos, Hillard M. Lazarus, Selina M. Luger, Letizia Foroni, Bela Patel, Adele K. Fielding, Ari Melnick, David I. Marks, Anthony V. Moorman, Peter H. Wiernik, Jacob M. Rowe, Martin S. Tallman, Anthony H. Goldstone, Charles G. Mullighan, Mark R. Litzow

Pathology Research and Scholarship

Genomic classification has improved risk assignment of pediatric, but not adult B-lineage acute lymphoblastic leukemia (B-ALL). The international UKALLXII/ECOG-ACRIN E2993 (#NCT00002514) trial accrued 1229 adolescent/adult patients with BCR-ABL1- B-ALL (aged 14 to 65 years). Although 93% of patients achieved remission, 41% relapsed at a median of 13 months (range, 28 days to 12 years). Five-year overall survival (OS) was 42% (95% confidence interval, 39, 44). Transcriptome sequencing, gene expression profiling, cytogenetics, and fusion polymerase chain reaction enabled genomic subtyping of 282 patient samples, of which 264 were eligible for trial, accounting for 64.5% of E2993 patients. Among patients with outcome …

Post-Concussion And Post-Traumatic Stress Symptoms After Pediatric Traumatic Brain Injury: Shared Vulnerability Factors?, Emily R Fisher, Janelle J Montroy, Gerardo Duque, Charles S Cox, Linda Ewing-Cobbs

Faculty, Staff and Student Publications

Following pediatric traumatic brain injury (TBI), post-concussion symptoms (PCS) and post-traumatic stress symptoms (PTSS) occur commonly; however, it is unknown to what degree they overlap. The study examined PCS and PTSS persisting 7 weeks after injury in children and adolescents ages 8-15 years with TBI (n = 89) or extracranial injury (EI; n = 40) after vehicle collisions. TBI was divided into mild, complicated-mild/moderate, and severe groups. Parents retrospectively rated children's pre-injury symptoms and behavior problems, and children completed self-report measures after injury. PCS and PTSS total scores were significantly correlated in TBI and EI groups, respectively, for child …