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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 Dec 2018

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 …


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 Dec 2018

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 …


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 Dec 2018

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 …


When Parents Have Misunderstandings About The Risks And Benefits Of Palliative Surgery., Berklee Robins, Adam Booser, John Lantos Dec 2018

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 …


Genetic Predisposition To Necrotizing Enterocolitis In Premature Infants: Current Knowledge, Challenges, And Future Directions., Alain Cuna, Lovya George, Venkatesh Sampath Dec 2018

Genetic Predisposition To Necrotizing Enterocolitis In Premature Infants: Current Knowledge, Challenges, And Future Directions., Alain Cuna, Lovya George, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

The role of genetics in the pathogenesis of necrotizing enterocolitis (NEC) was initially informed by epidemiological data indicating differences in prevalence among different ethnic groups as well as concordance in twins. These early observations, together with major advances in genomic research, paved the way for studies that begin to reveal the contribution of genetics to NEC. Using the candidate gene or pathway approach, several potential pathogenic variants for NEC in premature infants have already been identified. More recently, genome-wide association studies and exome-sequencing based studies for NEC have been reported. These advances, however, are tempered by the lack of adequately …


New Advances In Amblyopia Therapy Ii: Refractive Therapies, Courtney L Kraus, Susan M Culican Dec 2018

New Advances In Amblyopia Therapy Ii: Refractive Therapies, Courtney L Kraus, Susan M Culican

Open Access Publications

The treatment of anisometropic or ametropic amblyopia has traditionally enjoyed a high treatment success rate. Early initiation and consistent use of spectacle correction can completely resolve amblyopia in a majority of patients. For those with anisometropic amblyopia that fail to improve with glasses wear alone, patching or atropine penalisation can lead to equalisation of visual acuity. However, successful treatment requires full-time compliance with refractive correction and this can be a challenge for a patient population that often has one eye with good acuity without correction. Other barriers for a select population with high anisometropic or ametropic amblyopia include rejection of …


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 Nov 2018

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 Aβ1-42 levels were measured as a marker of AD, and fluid-attenuated inversion recovery imaging and diffusion tensor imaging were obtained to assess …


Financial Incentives For Smoking Treatment: Protocol Of The Fiesta Trial And Fiesta Oral Microbiome Substudy, Katherine M French, Sasha Z Gonzalez, Scott E Sherman, Alissa R Link, Sadozai Zoe Malik, Chi-Hong Tseng, Saahil A Jumkhawala, Briesny Tejada, Andrew White, Joseph A Ladapo Nov 2018

Financial Incentives For Smoking Treatment: Protocol Of The Fiesta Trial And Fiesta Oral Microbiome Substudy, Katherine M French, Sasha Z Gonzalez, Scott E Sherman, Alissa R Link, Sadozai Zoe Malik, Chi-Hong Tseng, Saahil A Jumkhawala, Briesny Tejada, Andrew White, Joseph A Ladapo

NYMC Student Publications

BACKGROUND: Smoking is the leading preventable cause of death in the United States, but evidence-based smoking cessation therapy is underutilized. Financial incentive strategies represent an innovative approach for increasing the use of counseling and pharmacotherapy. If effective, they could supplement or supplant resource-intensive policy options, particularly in populations for whom smoking has substantial societal costs. FIESTA (Financial IncEntives for Smoking TreAtment) will randomize hospitalized smokers to receive usual smoking cessation care alone or usual smoking care augmented with financial incentives. We aim to compare the impact of these two strategies on 1) smoking abstinence, 2) use of counseling and nicotine …


Unilateral, 3d Arm Movement Kinematics Are Encoded In Ipsilateral Human Cortex, David T. Bundy, Nicholas Szrama, Mrinal Pahwa, Eric C. Leuthardt Nov 2018

Unilateral, 3d Arm Movement Kinematics Are Encoded In Ipsilateral Human Cortex, David T. Bundy, Nicholas Szrama, Mrinal Pahwa, Eric C. Leuthardt

Open Access Publications

There is increasing evidence that the hemisphere ipsilateral to a moving limb plays a role in planning and executing movements. However, the exact relationship between cortical activity and ipsilateral limb movements is uncertain. We sought to determine whether 3D arm movement kinematics (speed, velocity, and position) could be decoded from cortical signals recorded from the hemisphere ipsilateral to the moving limb. By having invasively monitored patients perform unilateral reaches with each arm, we also compared the encoding of contralateral and ipsilateral limb kinematics from a single cortical hemisphere. In four motor-intact human patients (three male, one female) implanted with electrocorticography …


Micu1 Interacts With The D-Ring Of The Mcu Pore To Control Its Ca2+ Flux And Sensitivity To Ru360, Melanie Paillard, György Csordás, Kai-Ting Huang, Peter Várnai, Suresh K. Joseph, György Hajnóczky Nov 2018

Micu1 Interacts With The D-Ring Of The Mcu Pore To Control Its Ca2+ Flux And Sensitivity To Ru360, Melanie Paillard, György Csordás, Kai-Ting Huang, Peter Várnai, Suresh K. Joseph, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Proper control of the mitochondrial Ca2+ uniporter’s pore (MCU) is required to allow Ca2+ dependent activation of oxidative metabolism and to avoid mitochondrial Ca2+ overload and cell death. The MCU’s gatekeeping and cooperative activation is mediated by the Ca2+ sensing MICU1 protein, which has been proposed to form dimeric complexes anchored to the EMRE scaffold of MCU. We unexpectedly find that MICU1 suppresses inhibition of MCU by ruthenium red/Ru360, which bind to MCU’s DIME motif, the selectivity filter. This led us to recognize in MICU1’s sequence, a putative DIME Interacting Domain (DID) which is required for …


The Fatal Failure Of The Regulatory State, W. Kip Viscusi Nov 2018

The Fatal Failure Of The Regulatory State, W. Kip Viscusi

William & Mary Law Review

Although regulatory agencies place high values on the benefits associated with the reduction in mortality risks due to regulations, these same agencies substantially undervalue lives in their enforcement efforts. The disparity between the valuation of prospective risks and fatalities that have occurred is often by several orders of magnitude, diminishing whatever safety incentives the regulations might have generated. A review of the practices by the major federal agencies with responsibility for product safety and occupational safety finds that the value placed on fatalities in agencies’ regulatory analyses can be a factor of 1000 times greater than the magnitude of the …


Dysregulated Nk Cell Plcγ2 Signaling And Activity In Juvenile Dermatomyositis, Allison A Throm, Joshua B Alinger, Jeanette T Pingel, Allyssa L Daugherty, Lauren M Pachman, Anthony R French Nov 2018

Dysregulated Nk Cell Plcγ2 Signaling And Activity In Juvenile Dermatomyositis, Allison A Throm, Joshua B Alinger, Jeanette T Pingel, Allyssa L Daugherty, Lauren M Pachman, Anthony R French

Open Access Publications

Juvenile dermatomyositis (JDM) is a debilitating pediatric autoimmune disease manifesting with characteristic rash and muscle weakness. To delineate signaling abnormalities in JDM, mass cytometry was performed with PBMCs from treatment-naive JDM patients and controls. NK cell percentages were lower while frequencies of naive B cells and naive CD4+ T cells were higher in JDM patients than in controls. These cell frequency differences were attenuated with cessation of active disease. A large number of signaling differences were identified in treatment-naive JDM patients compared with controls. Classification models incorporating feature selection demonstrated that differences in phospholipase Cγ2 (PLCγ2) phosphorylation comprised 10 of …


Functional Brain Activation Changes Associated With Practice In Delaying Smoking Among Moderate To Heavy Smokers: Study Protocol And Rationale Of A Randomized Trial (Cope)., Andrew T. Fox, Delwyn Catley, Kimber P. Richter, Edward F. Ellerbeck, Morgan G. Brucks, Vlad B. Papa, Laura E. Martin Nov 2018

Functional Brain Activation Changes Associated With Practice In Delaying Smoking Among Moderate To Heavy Smokers: Study Protocol And Rationale Of A Randomized Trial (Cope)., Andrew T. Fox, Delwyn Catley, Kimber P. Richter, Edward F. Ellerbeck, Morgan G. Brucks, Vlad B. Papa, Laura E. Martin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Most smokers struggle to overcome tobacco addiction. Neuroscientific models of addiction emphasize the importance of brain regions associated with cognitive control and reward to understand the cycle of addiction and relapse. During an attempt at abstinence, the cognitive control system appears to be underpowered to override the heightened reward system of the addicted brain. Thus, one neural target for treatment is to strengthen the cognitive control system. It may be possible to improve the functioning of the cognitive control system via deliberate practice.

METHODS/DESIGN: This study will determine the effects of practicing delaying smoking on brain and behavioral measures …


Effects Of A Community Population Health Initiative On Blood Pressure Control In Latinos, James R Langabeer, Timothy D Henry, Carlos Perez Aldana, Larissa Deluna, Nora Silva, Tiffany Champagne-Langabeer Nov 2018

Effects Of A Community Population Health Initiative On Blood Pressure Control In Latinos, James R Langabeer, Timothy D Henry, Carlos Perez Aldana, Larissa Deluna, Nora Silva, Tiffany Champagne-Langabeer

Faculty, Staff and Student Publications

Background Hypertension remains one of the most important, modifiable cardiovascular risk factors. Yet, the largest minority ethnic group (Hispanics/Latinos) often have different health outcomes and behavior, making hypertension management more difficult. We explored the effects of an American Heart Association-sponsored population health intervention aimed at modifying behavior of Latinos living in Texas. Methods and Results We enrolled 8071 patients, and 5714 (65.7%) completed the 90-day program (58.5 years ±11.7; 59% female) from July 2016 to June 2018. Navigators identified patients with risk factors; initial and final blood pressure ( BP ) readings were performed in the physician's office; and interim …


Association Between Health Insurance Literacy And Avoidance Of Health Care Services Owing To Cost, Renuka Tipirneni, Mary C. Politi, Jeffrey T. Kullgren, Edith C. Kieffer, Susan D. Goold, Aaron M. Scherer Nov 2018

Association Between Health Insurance Literacy And Avoidance Of Health Care Services Owing To Cost, Renuka Tipirneni, Mary C. Politi, Jeffrey T. Kullgren, Edith C. Kieffer, Susan D. Goold, Aaron M. Scherer

Open Access Publications

Importance: Navigating health insurance and health care choices requires considerable health insurance literacy. Although recommended preventive services are exempt from out-of-pocket costs under the Affordable Care Act, many people may remain unaware of this provision and its effect on their required payment. Little is known about the association between individuals' health insurance literacy and their use of preventive or nonpreventive health care services.

Objective: To assess the association between health insurance literacy and self-reported avoidance of health care services owing to cost.

Design, Setting, and Participants: In this survey study, a US national, geographically diverse, nonprobability sample of 506 US …


Changes In The Us Burden Of Chronic Kidney Disease From 2002 To 2016: An Analysis Of The Global Burden Of Disease Study, Benjamin Bowe, Yan Xie, Tingting Li, Ali H. Mokdad, Hong Xian, Yan Yan, Geetha Maddukuri, Ziyad Al-Aly Nov 2018

Changes In The Us Burden Of Chronic Kidney Disease From 2002 To 2016: An Analysis Of The Global Burden Of Disease Study, Benjamin Bowe, Yan Xie, Tingting Li, Ali H. Mokdad, Hong Xian, Yan Yan, Geetha Maddukuri, Ziyad Al-Aly

Open Access Publications

Introduction: Over the past 15 years, changes in demographic, social, and epidemiologic trends occurred in the United States. These changes likely contributed to changes in chronic kidney disease (CKD) epidemiology.

Objective: To describe the change in burden of CKD at the US state level from 2002 to 2016.

Design, Setting, and Participants: This systematic analysis used data and methodologies from the 2016 Global Burden of Disease study in the United States. Data on CKD from 2002 to 2016 were examined at the state level.

Main Outcomes and Measures: Disability-adjusted life years (DALYs) and death due to CKD.

Results: In this …


Implementation Of Smart Pump Technology With Home Infusion Providers: An Assessment Of Clinician Workflow And Patient Satisfaction., Thomas D. Brown, Martha Michael, David S. Grady, Mary Ward Nov 2018

Implementation Of Smart Pump Technology With Home Infusion Providers: An Assessment Of Clinician Workflow And Patient Satisfaction., Thomas D. Brown, Martha Michael, David S. Grady, Mary Ward

Jefferson Hospital Staff Papers and Presentations

While hospitals have adopted smart pump technology (SPT) featuring drug libraries and medication safety software, most home infusion providers (HIPs) continue to use traditional infusion pumps that don't offer drug libraries or medication safety software. As infusion delivery is moving from the hospital to the home, the purpose of this study was to determine whether SPT was a feasible alternative at both a hospital-based and a rural HIP. HIP personnel were trained on an ambulatory infusion pump. Patients requiring home infusion used the pump and recorded daily pump interactions for 5 to 7 days. After the creation of a drug …


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 Nov 2018

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 …


Proteomics Of Human Liver Membrane Transporters: A Focus On Fetuses And Newborn Infants., Bianca D. Van Groen, Evita Van De Steeg, Miriam G. Mooij, Marola M H Van Lipzig, Barbara A E De Koning, Robert M. Verdijk, Heleen M. Wortelboer, R Gaedigk, Chengpeng Bi, J Steven Leeder, Ron H N Van Schaik, Joost Van Rosmalen, Dick Tibboel, Wouter H. Vaes, Saskia N. De Wildt Nov 2018

Proteomics Of Human Liver Membrane Transporters: A Focus On Fetuses And Newborn Infants., Bianca D. Van Groen, Evita Van De Steeg, Miriam G. Mooij, Marola M H Van Lipzig, Barbara A E De Koning, Robert M. Verdijk, Heleen M. Wortelboer, R Gaedigk, Chengpeng Bi, J Steven Leeder, Ron H N Van Schaik, Joost Van Rosmalen, Dick Tibboel, Wouter H. Vaes, Saskia N. De Wildt

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Hepatic membrane transporters are involved in the transport of many endogenous and exogenous compounds, including drugs. We aimed to study the relation of age with absolute transporter protein expression in a cohort of 62 mainly fetus and newborn samples.

METHODS: Protein expressions of BCRP, BSEP, GLUT1, MCT1, MDR1, MRP1, MRP2, MRP3, NTCP, OCT1, OATP1B1, OATP1B3, OATP2B1 and ATP1A1 were quantified with LC-MS/MS in isolated crude membrane fractions of snap-frozen post-mortem fetal and pediatric, and surgical adult liver samples. mRNA expression was quantified using RNA sequencing, and genetic variants with TaqMan assays. We explored relationships between protein expression and age …


Pharmacokinetics Of Ferric Pyrophosphate Citrate Administered Via Dialysate And Intravenously To Pediatric Patients On Chronic Hemodialysis., Raymond D. Pratt, Sarah Grimberg, Joshua J. Zaritsky, Bradley A. Warady Nov 2018

Pharmacokinetics Of Ferric Pyrophosphate Citrate Administered Via Dialysate And Intravenously To Pediatric Patients On Chronic Hemodialysis., Raymond D. Pratt, Sarah Grimberg, Joshua J. Zaritsky, Bradley A. Warady

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Iron deficiency is a common cause of anemia in pediatric patients with hemodialysis-dependent chronic kidney disease (CKD-5HD). Ferric pyrophosphate citrate (FPC, Triferic®) donates iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration. Administration of FPC via dialysate or intravenously (IV) may provide a suitable therapeutic option to current IV iron preparations for these patients.

METHODS: The pharmacokinetics and safety of FPC administered via dialysate and IV to patients aged < 6 years (n = 3), 6 to < 12 years (n = 4), and 12 to < 18 years (n = 15) were investigated in a multicenter, open-label, two-period, single-dose study. FPC (0.07 mg iron/kg) was infused IV into the venous blood return line during hemodialysis session no. 1. FPC iron was added to bicarbonate concentrate to deliver 2 μM (110 μg/L) iron via dialysate during hemodialysis session no. 2.

RESULTS: Mean serum total iron concentrations peaked 3 to 4 h after administration via dialysate and 2 to 4 h after IV administration and returned to baseline …


Trex1 Is Expressed By Microglia In Normal Human Brain And Increases In Regions Affected By Ischemia, Parul H Kothari, Grant R Kolar, Joanna C Jen, Rula Hajj-Ali, Paula Bertram, Robert E Schmidt, John P Atkinson Nov 2018

Trex1 Is Expressed By Microglia In Normal Human Brain And Increases In Regions Affected By Ischemia, Parul H Kothari, Grant R Kolar, Joanna C Jen, Rula Hajj-Ali, Paula Bertram, Robert E Schmidt, John P Atkinson

Open Access Publications

BACKGROUND: Mutations in the three-prime repair exonuclease 1 (TREX1) gene have been associated with neurological diseases, including Retinal Vasculopathy with Cerebral Leukoencephalopathy (RVCL). However, the endogenous expression of TREX1 in human brain has not been studied.

METHODS: We produced a rabbit polyclonal antibody (pAb) to TREX1 to characterize TREX1 by Western blotting (WB) of cell lysates from normal controls and subjects carrying an RVCL frame-shift mutation. Dual staining was performed to determine cell types expressing TREX1 in human brain tissue. TREX1 distribution in human brain was further evaluated by immunohistochemical analyses of formalin-fixed, paraffin-embedded samples from normal controls and patients …


Glasdegib In Combination With Cytarabine And Daunorubicin In Patients With Aml Or High-Risk Mds: Phase 2 Study Results, Jorge E Cortes, Mark A Schroeder, Et Al Nov 2018

Glasdegib In Combination With Cytarabine And Daunorubicin In Patients With Aml Or High-Risk Mds: Phase 2 Study Results, Jorge E Cortes, Mark A Schroeder, Et Al

Open Access Publications

Glasdegib is a Hedgehog pathway inhibitor. This ongoing, open-label, phase 2 study (NCT01546038) evaluated glasdegib plus cytarabine/daunorubicin in patients with untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS). Patients received glasdegib 100 mg orally, once daily in continuous 28-day cycles from day -3, with intravenous cytarabine 100 mg/m


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 Oct 2018

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 …


Genome-Wide Association Study Of Brain Amyloid Deposition As Measured By Pittsburgh Compound-B (Pib)-Pet Imaging, Qi Yan, Jorge L Del-Aguila, Carlos Cruchaga, Et Al Oct 2018

Genome-Wide Association Study Of Brain Amyloid Deposition As Measured By Pittsburgh Compound-B (Pib)-Pet Imaging, Qi Yan, Jorge L Del-Aguila, Carlos Cruchaga, Et Al

Open Access Publications

Deposition of amyloid plaques in the brain is one of the two main pathological hallmarks of Alzheimer's disease (AD). Amyloid positron emission tomography (PET) is a neuroimaging tool that selectively detects in vivo amyloid deposition in the brain and is a reliable endophenotype for AD that complements cerebrospinal fluid biomarkers with regional information. We measured in vivo amyloid deposition in the brains of ~1000 subjects from three collaborative AD centers and ADNI using


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 Oct 2018

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

Faculty, Staff and Student Publications

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 …


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 Oct 2018

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

Faculty, Staff and Student Publications

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 Oct 2018

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

Faculty, Staff and Student Publications

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 …


Understanding The Association Between Negative Symptoms And Performance On Effort-Based Decision-Making Tasks: The Importance Of Defeatist Performance Beliefs, L Felice Reddy, William P Horan, Deanna M Barch, Robert W Buchanan, James M Gold, Stephen R Marder, Jonathan K Wynn, Jared Young, Michael F Green Oct 2018

Understanding The Association Between Negative Symptoms And Performance On Effort-Based Decision-Making Tasks: The Importance Of Defeatist Performance Beliefs, L Felice Reddy, William P Horan, Deanna M Barch, Robert W Buchanan, James M Gold, Stephen R Marder, Jonathan K Wynn, Jared Young, Michael F Green

2010-2019 OA Pubs

Effort-based decision-making paradigms are increasingly utilized to gain insight into the nature of motivation deficits. Research has shown associations between effort-based decision making and experiential negative symptoms; however, the associations are not consistent. The current study had two primary goals. First, we aimed to replicate previous findings of a deficit in effort-based decision making among individuals with schizophrenia on a test of cognitive effort. Second, in a large sample combined from the current and a previous study, we sought to examine the association between negative symptoms and effort by including the related construct of defeatist beliefs. The results replicated previous …


Characteristics Of Adolescents Living With Hiv Receiving Care And Treatment Services In Antiretroviral Therapy Clinics In Cambodia: Descriptive Findings From A Cross-Sectional Study., Siyan Yi, Sovannary Tuot, Khuondyla Pal, Vohith Khol, Say Sok, Pheak Chhoun, Laura Ferguson, Gitau Mburu Oct 2018

Characteristics Of Adolescents Living With Hiv Receiving Care And Treatment Services In Antiretroviral Therapy Clinics In Cambodia: Descriptive Findings From A Cross-Sectional Study., Siyan Yi, Sovannary Tuot, Khuondyla Pal, Vohith Khol, Say Sok, Pheak Chhoun, Laura Ferguson, Gitau Mburu


BACKGROUND: Adolescents living with HIV experience worse HIV care outcomes compared to adults, especially during transition from pediatric to adult care. However, data regarding adolescents are limited. This paper describes and compares characteristics of male and female adolescents living with HIV preparing for transition from pediatric to adult care in Cambodia.

METHODS: This cross-sectional study was conducted in August 2016 among 328 adolescents aged 15-17, randomly selected from 11 antiretroviral therapy (ART) clinics. Data were collected using a structured questionnaire, and descriptive analyses were conducted to compare characteristics of male and female adolescents.

RESULTS: Of total, 55.2% were male, and …


Uncovering The Complex Genetics Of Human Character, Igor Zwir, Dragan M Svrakic, Sandor Rozsa, Maribel Martinez, C Robert Cloninger, Et Al Oct 2018

Uncovering The Complex Genetics Of Human Character, Igor Zwir, Dragan M Svrakic, Sandor Rozsa, Maribel Martinez, C Robert Cloninger, Et Al

Open Access Publications

Human personality is 30-60% heritable according to twin and adoption studies. Hundreds of genetic variants are expected to influence its complex development, but few have been identified. We used a machine learning method for genome-wide association studies (GWAS) to uncover complex genotypic-phenotypic networks and environmental interactions. The Temperament and Character Inventory (TCI) measured the self-regulatory components of personality critical for health (i.e., the character traits of self-directedness, cooperativeness, and self-transcendence). In a discovery sample of 2149 healthy Finns, we identified sets of single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (i.e., SNP sets) regardless of phenotype. Second, we identified five …