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Rheumatoid Meningitis Sine Arthritis., Cathy Lee-Ching, Lawrence C. Kenyon, Matthew Berk, Chantel Park

Department of Medicine Faculty Papers

Rheumatoid meningitis is a rare and very serious extra-articular manifestation of rheumatoid arthritis. We present a case of a 7()year-old female with no history of arthritis who developed stroke-like symptoms, seizures, psychosis and compulsive behavior. Serial brain magnetic resonance images (MRI) over four months demonstrated progressive interhemispheric meningeal thickening. She had mild lymphocytic pleocytosis on the cerebrospinal fluid analysis and serum anti-cyclic citrullinated peptide antibodies resulted positive in high titers. She underwent a brain biopsy showing necrotizing granulomas consistent with rheumatoid meningitis. Her symptoms resolved with treatment with glucocorticoids and cyclophosphamide. She has not been diagnosed with rheumatoid arthritis even …

Clinical Pharmacology Of Tisagenlecleucel In B-Cell Acute Lymphoblastic Leukemia., Karen Thudium Mueller, Edward Waldron, Stephan A. Grupp, John E. Levine, Theodore W. Laetsch, Michael A. Pulsipher, Michael W. Boyer, Keith August, Jason Hamilton, Rakesh Awasthi, Andrew M. Stein, Denise Sickert, Abhijit Chakraborty, Bruce L. Levine, Carl H. June, Lori Tomassian, Sweta S. Shah, Mimi Leung, Tetiana Taran, Patricia A. Wood, Shannon L. Maude

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR19) T-cell therapy approved for the treatment of children and young adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL).

PATIENTS AND METHODS: We evaluated the cellular kinetics of tisagenlecleucel, the effect of patient factors, humoral immunogenicity, and manufacturing attributes on its kinetics, and exposure-response analysis for efficacy, safety and pharmacodynamic endpoints in 79 patients across two studies in pediatric B-ALL (ELIANA and ENSIGN).

RESULTS: Using quantitative polymerase chain reaction to quantify levels of tisagenlecleucel transgene, responders (N = 62) had ≈2-fold higher tisagenlecleucel expansion in peripheral blood than nonresponders ( …

"C.H.A.M.P. Families": Description And Theoretical Foundations Of A Paediatric Overweight And Obesity Intervention Targeting Parents-A Single-Centre Non-Randomised Feasibility Study., Kristen Reilly, Trish Tucker, Jennifer D. Irwin Phd, Andrew Johnson, Erin S Pearson, Dirk E Bock, Shauna M. Burke

Paediatrics Publications

Childhood obesity represents a significant global health challenge, and treatment interventions are needed. The purpose of this paper is to describe the components and theoretical model that was used in the development and implementation of a unique parent-focussed paediatric overweight/obesity intervention. C.H.A.M.P. Families was a single-centre, prospective intervention offered to parents of children aged between 6⁻14 years with a body mass index (BMI) ≥85th percentile for age and sex. The intervention included: (1) eight group-based (parent-only) education sessions over 13-weeks; (2) eight home-based activities; and (3) two group-based (family) follow-up support sessions. The first section of the manuscript contains a …

Social Determinants Of Health And What Mothers Say They Need And Want After Release From Jail., Elisabeth Stelson, Marjie Mogul, Holly Harner, Jeane Ann Grisso, Rosemary Frasso Phd, Msc, Cph

College of Population Health Faculty Papers

Identifying the biopsychosocial needs of mothers who have been released from jail is critical to understanding the best ways to support their health and stability after release. In May through August 2014, we interviewed 15 mothers who had been released from an urban jail about their reentry experiences, and we analyzed transcripts for themes. Eight domains of community reentry emerged through analysis: behavioral health services, education, employment, housing, material resources, medical care, relationships with children, and social support. Participants defined barriers to successful reentry, which paralleled the social determinants of health, and shared suggestions that could be used to mitigate …

Targeting The Brd4/Foxo3a/Cdk6 Axis Sensitizes Akt Inhibition In Luminal Breast Cancer, Jingyi Liu, Weijie Guo, Zhibing Duan, Lei Zeng, Yadi Wu, Yule Chen, Fang Tai, Yifan Wang, Yiwei Lin, Qiang Zhang, Yanling He, Jiong Deng, Rachel L. Stewart, Chi Wang, Pengnian Charles Lin, Saghi Ghaffari, B. Mark Evers, Suling Liu, Ming-Ming Zhou, Binhua P. Zhou, Jian Shi

Molecular and Cellular Biochemistry Faculty Publications

BRD4 assembles transcriptional machinery at gene super-enhancer regions and governs the expression of genes that are critical for cancer progression. However, it remains unclear whether BRD4-mediated gene transcription is required for tumor cells to develop drug resistance. Our data show that prolonged treatment of luminal breast cancer cells with AKT inhibitors induces FOXO3a dephosphorylation, nuclear translocation, and disrupts its association with SirT6, eventually leading to FOXO3a acetylation as well as BRD4 recognition. Acetylated FOXO3a recognizes the BD2 domain of BRD4, recruits the BRD4/RNAPII complex to the CDK6 gene promoter, and induces its transcription. Pharmacological inhibition of either BRD4/FOXO3a association or …

Morphometric Characteristics And Time To Hatch As Efficacious Indicators For Potential Nanotoxicity Assay In Zebrafish, Seyed-Mohammadreza Samaee, Nafiseh Manteghi, Robert A. Yokel, Mohammad Reza Mohajeri-Tehrani

Pharmaceutical Sciences Faculty Publications

Although the effects of nano-sized titania (nTiO₂) on hatching events (change in hatching time and total hatching) in zebrafish have been reported, additional consequences of nTiO₂ exposure (i.e., the effects of nTiO₂-induced changes in hatching events and morphometric parameters on embryo-larvae development and survivability) have not been reported. To address this knowledge gap, embryos 4 h postfertilization were exposed to nTiO₂ (0, 0.01, 10, and 1000 μg/mL) for 220 h. Hatching rate (58, 82, and 106 h postexposure [hpe]), survival rate (8 times from 34 to 202 hpe), and 21 morphometric characteristics (8 times …

Phenytoin Activates Smad3 Phosphorylation And Periostin Expression In Drug-Induced Gingival Enlargement., Shawna S Kim, Georgia Nikoloudaki, Mark Darling, Michael J Rieder, Douglas W Hamilton

Paediatrics Publications

Drug-induced gingival enlargement (DIGE) is a fibrotic condition associated with systemic administration of the anti-epileptic drug, phenytoin. We have previously demonstrated that periostin, which is transforming growth factor-beta (TGF-β) inducible gene, is upregulated in various fibrotic conditions including gingival enlargement associated with nifedipine. The objective of this study was to assess periostin expression in phenytoin-induced gingival enlargement (PIGE) tissues and to investigate the mechanisms underlying periostin expression. Human PIGE tissues were assessed using Masson's trichrome, with cell infiltration and changes in extracellular matrix composition characterized through labeling with antibodies to periostin, phospho-SMAD 3, TGF-β, as well as the macrophage markers …

The Impact Of Pulmonary Hypertension In Preterm Infants With Severe Bronchopulmonary Dysplasia Through 1 Year., Joanne M. Lagatta, Erik B. Hysinger, Isabella Zaniletti, Erica M. Wymore, Shilpa Vyas-Read, Sushmita Yallapragada, Leif D. Nelin, William E. Truog, Michael A. Padula, Nicolas F M Porta, Rashmin C. Savani, Karin P. Potoka, Steven M. Kawut, Robert Digeronimo, Girija Natarajan, Huayan Zhang, Theresa R. Grover, William A. Engle, Karna Murthy, Children's Hospital Neonatal Consortium Severe Bpd Focus Group

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To assess the effect of pulmonary hypertension on neonatal intensive care unit mortality and hospital readmission through 1 year of corrected age in a large multicenter cohort of infants with severe bronchopulmonary dysplasia.

STUDY DESIGN: This was a multicenter, retrospective cohort study of 1677 infants bornChildren's Hospital Neonatal Consortium with records linked to the Pediatric Health Information System.

RESULTS: Pulmonary hypertension occurred in 370 out of 1677 (22%) infants. During the neonatal admission, pulmonary hypertension was associated with mortality (OR 3.15, 95% CI 2.10-4.73, P < .001), ventilator support at 36 weeks of postmenstrual age (60% vs 40%, P < .001), duration of ventilation (72 IQR 30-124 vs 41 IQR 17-74 days, P < .001), and higher respiratory severity score (3.6 IQR 0.4-7.0 vs 0.8 IQR 0.3-3.3, P < .001). At discharge, pulmonary hypertension was associated with tracheostomy (27% vs 9%, P < .001), supplemental oxygen use (84% vs 61%, P < .001), and tube feeds (80% vs 46%, P < .001). Through 1 year of corrected age, pulmonary hypertension was associated with increased frequency of readmission (incidence rate ratio [IRR] = 1.38, 95% CI 1.18-1.63, P < .001).

CONCLUSIONS: Infants with severe bronchopulmonary dysplasia-associated pulmonary hypertension have increased morbidity and mortality through …

When Parents Have Misunderstandings About The Risks And Benefits Of Palliative Surgery., Berklee Robins, Adam Booser, John Lantos

Manuscripts, Articles, Book Chapters and Other Papers

When a child needs surgery, both the surgeon and the anesthesiologist must obtain informed consent from the parents. In theory, each specialist obtains permission for their respective portion of the procedure, with the anesthesiologist only obtaining informed consent for the administration of anesthesia and management in the operating room and recovery room. However, he or she may occasionally realize that the parents have misunderstandings about what the surgery and perioperative course entail. In such cases, he or she must decide whether their role is only to discuss the issues related to anesthesia care or whether he or she should also …

Evaluation Of The Hiv Infant Tracking System (Hitsystem) To Optimise Quality And Efficiency Of Early Infant Diagnosis: A Cluster-Randomised Trial In Kenya., Sarah Finocchario-Kessler, Brad Gautney, Anlin Cheng, Catherine Wexler, May Maloba, Niaman Nazir, Samoel Khamadi, Raphael Lwembe, Melinda Brown, Thomas A. Odeny, Jacinda K. Dariotis, Matthew Sandbulte, Natabhona Mabachi, Kathy Goggin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The HIV Infant Tracking System (HITSystem) is a web-based intervention linking providers of early infant diagnosis, laboratory technicians, and mothers and infants to improve outcomes for HIV-exposed infants. We aimed to evaluate the efficacy of the HITSystem on key outcomes of early infant diagnosis.

METHODS: We did a cluster-randomised trial at six hospitals in Kenya, which were matched on geographic region, resource level, and volume of patients (high, medium, and low). We randomly allocated hospitals within a matched pair to either the HITSystem (intervention; n=3) or standard of care (control; n=3). A random number generator was used to assign …

Child Abuse, Incarceration, And Decisions About Life-Sustaining Treatment., Paul C. Mann, Elliott Mark Weiss, Rebecca R. Seltzer, Rachel A B Dodge, Renee D. Boss, John Lantos

Manuscripts, Articles, Book Chapters and Other Papers

Most critical care interventions for children occur in the framework of a supportive environment with loving parents that are present at the bedside to help to guide medical interventions through shared decision-making. What happens, however, if the parents are precluded from being at the bedside because of legal entanglements? How should clinical decisions progress in those cases? In this Ethics Rounds, we present the case of an infant with severe hypoxic-ischemic encephalopathy at birth whose mother was incarcerated shortly after delivery. We explore clinical and legal challenges that the medical team faces in determining best interests for the infant in …

A Multicenter Study To Evaluate Pulmonary Function In Osteogenesis Imperfecta., Allison Tam, Shan Chen, Evan Schauer, Ingo Grafe, Venkata Bandi, Jay R. Shapiro, Robert D. Steiner, Peter A. Smith, Michael B. Bober, Tracy Hart, David Cuthbertson, Jeffrey Krischer, Mary Mullins, Peter H. Byers, Robert A. Sandhaus, Michaela Durigova, Francis H. Glorieux, Frank Rauch, Vernon Reid Sutton, Brendan Lee, Members Of The Brittle Bone Disorders Consortium, Eric T. Rush, Sandesh C S Nagamani

Manuscripts, Articles, Book Chapters and Other Papers

Pulmonary complications are a significant cause for morbidity and mortality in osteogenesis imperfecta (OI). However, to date, there have been few studies that have systematically evaluated pulmonary function in individuals with OI. We analyzed spirometry measurements, including forced vital capacity (FVC) and forced expiratory volume in the first second (FEV₁ ), in a large cohort of individuals with OI (n = 217) enrolled in a multicenter, observational study. We show that individuals with the more severe form of the disease, OI type III, have significantly reduced FVC and FEV₁ which do not follow the expected trends of the …

Risk Stratification Of Febrile Infants ≤60 Days Old Without Routine Lumbar Puncture., Paul L. Aronson, Marie E. Wang, Eugene D. Shapiro, Samir S. Shah, Adrienne G. Deporre, Russell J Mcculloh, Christopher M. Pruitt, Sanyukta Desai, Lise E. Nigrovic, Richard D. Marble, Rianna C. Leazer, Sahar N. Rooholamini, Laura F. Sartori, Fran Balamuth, Christopher Woll, Mark I. Neuman, Febrile Young Infant Research Collaborative

Manuscripts, Articles, Book Chapters and Other Papers

Video Abstract: media-1vid110.1542/5840460609001PEDS-VA_2018-1879

OBJECTIVES: To evaluate the Rochester and modified Philadelphia criteria for the risk stratification of febrile infants with invasive bacterial infection (IBI) who do not appear ill without routine cerebrospinal fluid (CSF) testing.

METHODS: We performed a case-control study of febrile infants ≤60 days old presenting to 1 of 9 emergency departments from 2011 to 2016. For each infant with IBI (defined as a blood [bacteremia] and/or CSF [bacterial meningitis] culture with growth of a pathogen), controls without IBI were matched by site and date of visit. Infants were excluded if they appeared ill or had a …

Rapid And Robust Restoration Of Breathing Long After Spinal Cord Injury, Philippa M. Warren, Stephanie C. Steiger, Thomas E. Dick, Peter M. Macfarlane, Warren J. Alilain, Jerry Silver

Spinal Cord and Brain Injury Research Center Faculty Publications

There exists an abundance of barriers that hinder functional recovery following spinal cord injury, especially at chronic stages. Here, we examine the rescue of breathing up to 1.5 years following cervical hemisection in the rat. In spite of complete hemidiaphragm paralysis, a single injection of chondroitinase ABC in the phrenic motor pool restored robust and persistent diaphragm function while improving neuromuscular junction anatomy. This treatment strategy was more effective when applied chronically than when assessed acutely after injury. The addition of intermittent hypoxia conditioning further strengthened the ventilatory response. However, in a sub-population of animals, this combination treatment caused excess …

Distinct White Matter Changes Associated With Cerebrospinal Fluid Amyloid-Β1-42 And Hypertension, Omar M. Al-Janabi, Christopher A. Brown, Ahmed A. Bahrani, Erin L. Abner, Justin M. Barber, Brian T. Gold, Larry B. Goldstein, Richard R. Murphy, Peter T. Nelson, Nathan F. Johnson, Leslie M. Shaw, Charles D. Smith, John Q. Trojanowski, Donna M. Wilcock, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Alzheimer's disease (AD) pathology and hypertension (HTN) are risk factors for development of white matter (WM) alterations and might be independently associated with these alterations in older adults.

OBJECTIVE: To evaluate the independent and synergistic effects of HTN and AD pathology on WM alterations.

METHODS: Clinical measures of cerebrovascular disease risk were collected from 62 participants in University of Kentucky Alzheimer's Disease Center studies who also had cerebrospinal fluid (CSF) sampling and MRI brain scans. CSF Aβ_1-42 levels were measured as a marker of AD, and fluid-attenuated inversion recovery imaging and diffusion tensor imaging were obtained to assess …

Multicenter Trial Of A Combination Probiotic For Children With Gastroenteritis., Stephen B Freedman, Sarah Williamson-Urquhart, Ken J Farion, Serge Gouin, Andrew R Willan, Naveen Poonai, Katrina Hurley, Philip M Sherman, Yaron Finkelstein, Bonita E Lee, Xiao-Li Pang, Linda Chui, David Schnadower, Jianling Xie, Marc Gorelick, Suzanne Schuh

Paediatrics Publications

Background

Gastroenteritis accounts for approximately 1.7 million visits to the emergency department (ED) by children in the United States every year. Data to determine whether the use of probiotics improves outcomes in these children are lacking.

Methods

We conducted a randomized, double-blind trial involving 886 children 3 to 48 months of age with gastroenteritis who presented to six pediatric EDs in Canada. Participants received a 5-day course of a combination probiotic product containing Lactobacillus rhamnosus R0011 and L. helveticus R0052, at a dose of 4.0×10

Results

Moderate-to-severe gastroenteritis within 14 days after enrollment occurred in 108 of 414 participants (26.1%) …

One-Day Oral Polyethylene Glycol Based Cleanout Is Effective For Pre-Colonoscopy Preparation In Children., Ashwath S. Kumar, Brooke L. Beutler, Thomas M. Attard

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The adequacy of pre-procedure preparation is the principal determinant of the quality of colonoscopy in pediatric as in adult patients. There is a lack of consensus, among providers on a standard pre-procedure regimen. Professional society guidelines include the use of Polyethylene glycol (PEG). Herein we report on the provider-assessed adequacy of a one day, age-categorized dosing, PEG based cleanout regimen in children undergoing colonoscopy in a tertiary institution.

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METHODS: The standard bowel preparation regime at our institution includes an age dependent minimum PEG dosing regimen in addition to clear liquids the day prior to the procedure. We retrospectively …

Blood Transfusions In Preterm Infants: Changes On Perfusion Index And Intermittent Hypoxemia, Katrina T. Ibonia, Henrietta S. Bada, Philip M. Westgate, Enrique Gomez Pomar, Prasad Bhandary, Abhijit R. Patwardhan, Elie G. Abu Jawdeh

Pediatrics Faculty Publications

BACKGROUND

Red blood cell (RBC) transfusion decreases intermittent hypoxemia (IH) events beyond the first week of life. This benefit may be related to improved perfusion to the respiratory control network. Perfusion index (PI) is a perfusion measure provided by the pulse oximeter. We hypothesized that the benefit in IH after RBC transfusion is associated with an increase in PI. In addition, we assessed the value of PI and clinical measures in predicting the effect of RBC transfusion on IH.

STUDY DESIGN AND METHODS

We prospectively enrolled infants less than 30 weeks' gestation age. PI and oxygen saturation (SpO₂) …

Continuous Glucose Monitoring And Glycemic Control Among Youth With Type 1 Diabetes: International Comparison From The T1d Exchange And Dpv Initiative., Daniel Jj Desalvo, Kellee M. Miller, Julia M. Hermann, David M. Maahs, Sabine E. Hofer, Mark A. Clements, Eggert Lilienthal, Jennifer L. Sherr, Martin Tauschmann, Reinhard W. Holl, T1d Exchange And Dpv Registries

Manuscripts, Articles, Book Chapters and Other Papers

Background: To assess the change in rates of pediatric real-time or intermittent scanning continuous glucose monitoring (CGM) use over the past 5 years, and how it impacts glycemic control, data from two registries were compared: the US-based type 1 diabetes Exchange Registry (T1DX) and the German/Austrian DPV (Prospective Diabetes Follow-Up Registry).

Methods: Registry participants aged≥1 year encompassed 29 007 individuals in 2011 and 29 150 participants in 2016. Demographic data, CGM use and hemoglobin A1c (HbA1c) were obtained from medical records.

Results: CGM use increased from 2011 to 2016 in both registries across all age groups, regardless of gender, ethnic …

Pediatric Cardioembolic Stroke In Midaortic Syndrome, Ana C. Albuja, Mauricio F. Villamar, Alejandra M. Stewart, Donita D. Lightner

Neurology Faculty Publications

No abstract provided.

Duet: A Phase 2 Study Evaluating The Efficacy And Safety Of Sparsentan In Patients With Fsgs., Howard Trachtman, Peter Nelson, Sharon Adler, Kirk N. Campbell, Abanti Chaudhuri, Vimal Kumar Derebail, Giovanni Gambaro, Loreto Gesualdo, Debbie S. Gipson, Jonathan Hogan, Kenneth Lieberman, Brad Marder, Kevin Edward Meyers, Esmat Mustafa, Jai Radhakrishnan, Tarak Srivastava, Miganush Stepanians, Vladimír Tesar, Olga Zhdanova, Radko Komers, Duet Study Group

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: We evaluated and compared the effects of sparsentan, a dual endothelin type A (ETA) and angiotensin II type 1 receptor antagonist, with those of the angiotensin II type 1 receptor antagonist irbesartan in patients with primary FSGS.

METHODS: In this phase 2, randomized, double-blind, active-control Efficacy and Safety of Sparsentan (RE-021), a Dual Endothelin Receptor and Angiotensin Receptor Blocker, in Patients with Focal Segmental Glomerulosclerosis (FSGS): A Randomized, Double-blind, Active-Control, Dose-Escalation Study (DUET), patients aged 8-75 years with biopsy-proven FSGS, eGFR>30 ml/min per 1.73 m2, and urinary protein-to-creatinine ratio (UP/C) ≥1.0 g/g received sparsentan (200, 400, or 800 …

Azithromycin For Early Pseudomonas Infection In Cystic Fibrosis. The Optimize Randomized Trial., Nicole Mayer-Hamblett, George Retsch-Bogart, Margaret Kloster, Frank Accurso, Margaret Rosenfeld, Gary Albers, Philip Black, Perry Brown, Annemarie Cairns, Stephanie D. Davis, Gavin R. Graff, Gwendolyn S. Kerby, David Orenstein, Rachael Buckingham, Bonnie W. Ramsey, Optimize Study Group

Manuscripts, Articles, Book Chapters and Other Papers

RATIONALE: New isolation of Pseudomonas aeruginosa (Pa) is generally treated with inhaled antipseudomonal antibiotics such as tobramycin inhalation solution (TIS). A therapeutic approach that complements traditional antimicrobial therapy by reducing the risk of pulmonary exacerbation and inflammation may ultimately prolong the time to Pa recurrence.

OBJECTIVES: To test the hypothesis that the addition of azithromycin to TIS in children with cystic fibrosis and early Pa decreases the risk of pulmonary exacerbation and prolongs the time to Pa recurrence.

METHODS: The OPTIMIZE (Optimizing Treatment for Early Pseudomonas aeruginosa Infection in Cystic Fibrosis) trial was a multicenter, double-blind, randomized, placebo-controlled, 18-month trial …

Rationale, Design And Methods Of "Set The Rules": A Tailored Peer-To-Peer Health Information Intervention, Jennifer R. Warren, Brandi M. White

Health and Clinical Sciences Faculty Publications

Ensuring equitable access to health information is one strategy to promote health equity for underserved communities, especially for low-income African Americans (AAs). Childcare centers are one viable site to deliver health information to address this disparity. This paper describes the methods used in a community-based participatory research project with a childcare facility that aimed to reduce environmental tobacco smoke (ETS) exposure among low-income AA children. Through collaboration and multiple data collection methods, partners identified communication strategies to overcome informational barriers. These initial findings indicated a peer-to-peer health information intervention, entitled “Set the Rules”, as the best strategy to increase awareness. …

Collagen Prolyl 4-Hydroxylase 1 Is Essential For Hif-1Α Stabilization And Tnbc Chemoresistance, Gaofeng Xiong, Rachel L. Stewart, Jie Chen, Tianyan Gao, Timothy L. Scott, Luis M. Samayoa, Kathleen L. O'Connor, Andrew N. Lane, Ren Xu

Markey Cancer Center Faculty Publications

Collagen prolyl 4-hydroxylase (P4H) expression and collagen hydroxylation in cancer cells are necessary for breast cancer progression. Here, we show that P4H alpha 1 subunit (P4HA1) protein expression is induced in triple-negative breast cancer (TNBC) and HER2 positive breast cancer. By modulating alpha ketoglutarate (α-KG) and succinate levels P4HA1 expression reduces proline hydroxylation on hypoxia-inducible factor (HIF) 1α, enhancing its stability in cancer cells. Activation of the P4HA/HIF-1 axis enhances cancer cell stemness, accompanied by decreased oxidative phosphorylation and reactive oxygen species (ROS) levels. Inhibition of P4HA1 sensitizes TNBC to the chemotherapeutic agent docetaxel and doxorubicin in xenografts and patient-derived …

High Report Of Miscarriage Among Women Living With Hiv Who Want To Conceive In Uganda., Sarah Finocchario-Kessler, Kathy Goggin, Vincent S. Staggs, Rhoda K. Wanyenze, Jolly Beyeza-Kashesya, Deborah Mindry, Josephine Birungi, Glenn J Wagner

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Data on early miscarriage incidence is limited due to various social and methodological barriers. We report on 24-month pregnancy outcomes of 299 female Ugandan HIV clients in committed relationships with an intention to conceive. Miscarriage data are reported as auxiliary findings to a larger study (5R01HD072633).

RESULTS: 127 (42%) participants reported a pregnancy during the study; among the remaining 172, 82 indicated they stopped trying to conceive, and 16 dropped out prior to month 24. Of the 127 pregnancies, 55 (43%) resulted in live births, 67 (53%) in spontaneous miscarriage, 1 (< 1%) in stillbirth, 1 (< 1%) in abortion, and 3 (2%) in unknown outcomes. Three-quarters (75%) of miscarriages for which time until miscarriage was available were reported to occur in the first trimester (mean = 11.3 weeks gestation). The 67 participants who reported a miscarriage tended to be older (mean 33 vs. 30 years), but the significance of age did not persist after adjusting for multiple tests. We observed relatively low rates of pregnancy and high rates of miscarriage among this cohort of HIV-positive women wanting to conceive. Rigorously designed studies are needed to better understand the observed high rate of early miscarriage among HIV-infected women.

Exome Sequencing Identifies Gene Variants And Networks Associated With Extreme Respiratory Outcomes Following Preterm Birth, Aaron Hamvas, Rui Feng, Yingtao Bi, Fan Wang, Soumyaroop Bhattacharya, Jared Mereness, Madhurima Kaushal, C Michael Cotten, Philip L Ballard, Thomas J Mariani

Journal Articles

BACKGROUND: Previous studies have identified genetic variants associated with bronchopulmonary dysplasia (BPD) in extremely preterm infants. However, findings with genome-wide significance have been rare, and not replicated. We hypothesized that whole exome sequencing (WES) of premature subjects with extremely divergent phenotypic outcomes could facilitate the identification of genetic variants or gene networks contributing disease risk.

RESULTS: The Prematurity and Respiratory Outcomes Program (PROP) recruited a cohort of > 765 extremely preterm infants for the identification of markers of respiratory morbidity. We completed WES on 146 PROP subjects (85 affected, 61 unaffected) representing extreme phenotypes of early respiratory morbidity. We tested for …

The Impact Of Stuttering On Development Of Self-Identity, Relationships, And Quality Of Life In Women Who Stutter, Charn Nang, Deborah J. Hersh, Katie Milton, Su Re Lau

Research outputs 2014 to 2021

Purpose: The experiences of women who stutter have been underresearched. Clinicians have little guidance from the research literature on issues specific to women who stutter and are likely to have less clinical contact with this group than with men who stutter because of the higher prevalence of stuttering in men. This study explored the experiences of a small group of women who stutter with a particular focus on what the main current issues are and how gender may have influenced experiences with stuttering.

Method: This qualitative study involved recruitment of 9 women who stutter (aged 35-80 years) through a support …

Effect Of Aspirin On Cardiovascular Events And Bleeding In The Healthy Elderly, John J Mcneil, Rory Wolfe, Robyn L Woods, Andrew M Tonkin, Geoffrey A Donnan, Mark R Nelson, Christopher M Reid, Jessica E Lockery, Brenda Kirpach, Elsdon Storey, Raj C Shah, Jeff D Williamson, Karen L Margolis, Michael E Ernst, Walter P Abhayaratna, Nigel Stocks, Sharyn M Fitzgerald, Suzanne G Orchard, Ruth E Trevaks, Lawrence J Beilin, Colin I Johnston, Joanne Ryan, Barbara Radziszewska, Michael Jelinek, Mobin Malik, Charles B Eaton, Donna Brauer, Geoff Cloud, Erica M Wood, Suzanne E Mahady, Suzanne Satterfield, Richard Grimm, Anne M Murray

Journal Articles

BACKGROUND: Aspirin is a well-established therapy for the secondary prevention of cardiovascular events. However, its role in the primary prevention of cardiovascular disease is unclear, especially in older persons, who have an increased risk.

METHODS: From 2010 through 2014, we enrolled community-dwelling men and women in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or disability. Participants were randomly assigned to receive 100 mg of enteric-coated aspirin or placebo. The primary end point was a …

Effect Of Aspirin On All-Cause Mortality In The Healthy Elderly, John J Mcneil, Mark R Nelson, Robyn L Woods, Jessica E Lockery, Rory Wolfe, Christopher M Reid, Brenda Kirpach, Raj C Shah, Diane G Ives, Elsdon Storey, Joanne Ryan, Andrew M Tonkin, Anne B Newman, Jeff D Williamson, Karen L Margolis, Michael E Ernst, Walter P Abhayaratna, Nigel Stocks, Sharyn M Fitzgerald, Suzanne G Orchard, Ruth E Trevaks, Lawrence J Beilin, Geoffrey A Donnan, Peter Gibbs, Colin I Johnston, Barbara Radziszewska, Richard Grimm, Anne M Murray

Journal Articles

BACKGROUND: In the primary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, now published in the Journal, we report that the daily use of aspirin did not provide a benefit with regard to the primary end point of disability-free survival among older adults. A numerically higher rate of the secondary end point of death from any cause was observed with aspirin than with placebo.

METHODS: From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics …

Effect Of Aspirin On Disability-Free Survival In The Healthy Elderly, John J Mcneil, Robyn L Woods, Mark R Nelson, Christopher M Reid, Brenda Kirpach, Rory Wolfe, Elsdon Storey, Raj C Shah, Jessica E Lockery, Andrew M Tonkin, Anne B Newman, Jeff D Williamson, Karen L Margolis, Michael E Ernst, Walter P Abhayaratna, Nigel Stocks, Sharyn M Fitzgerald, Suzanne G Orchard, Ruth E Trevaks, Lawrence J Beilin, Geoffrey A Donnan, Peter Gibbs, Colin I Johnston, Joanne Ryan, Barbara Radziszewska, Richard Grimm, Anne M Murray

Journal Articles

BACKGROUND: Information on the use of aspirin to increase healthy independent life span in older persons is limited. Whether 5 years of daily low-dose aspirin therapy would extend disability-free life in healthy seniors is unclear.

METHODS: From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or physical disability. Participants were randomly assigned to receive 100 mg per day of enteric-coated aspirin or placebo orally. The primary end …