Digital Commons Network^™

Sex And Race And/Or Ethnicity Differences In Patients Undergoing Radiofrequency Ablation For Barrett's Esophagus: Results From The U.S. Rfa Registry., Sarina Pasricha, Nan Li, William J. Bulsiewicz, Richard I. Rothstein, Anthony Infantolino, Atilla Ertan, Daniel S. Camara, Evan S. Dellon, George Triadafilopoulos, Charles J. Lightdale, Ryan D. Madanick, William D. Lyday, Raman V. Muthusamy, Bergein F. Overholt, Nicholas J. Shaheen

Department of Medicine Faculty Papers

BACKGROUND: Little is known about differences in Barrett's esophagus (BE) characteristics by sex and race and/or ethnicity or these differences in response to radiofrequency ablation (RFA).

OBJECTIVE: We compared disease-specific characteristics, treatment efficacy, and safety outcomes by sex and race and/or ethnicity in patients treated with RFA for BE.

DESIGN: The U.S. RFA patient registry is a multicenter collaboration reporting processes and outcomes of care for patients treated with RFA for BE.

PATIENTS: Patients enrolled with BE.

INTERVENTIONS: RFA.

MAIN OUTCOME MEASUREMENTS: We assessed safety (stricture, bleeding, perforation, hospitalization), efficacy (complete eradication of intestinal metaplasia [CEIM]), complete eradication of dysplasia, …

Association Between Arsenic Exposure From Drinking Water And Longitudinal Change In Blood Pressure Among Heals Cohort Participants, Jieying Jiang, Mengling Liu, Faruque Parvez, Binhuan Wang, Fen Wu, Mahbub Eunus, Sripal Bangalore, Jonathan D. Newman, Alauddin Ahmed, Tariqul Islam, Muhammed Rakibuz-Zaman, Rabiul Hasan, Golam Sarwar, Diane Levy, Vesna Slavkovich, Maria Argos, Molly Scannell Bryan, Shohreh F. Farzan, Richard B. Hayes, Joseph H. Graziano, Habibul Ahsan, Yu Chen

Dartmouth Scholarship

Background:

Cross-sectional studies have shown associations between arsenic exposure and prevalence of high blood pressure; however, studies examining the relationship of arsenic exposure with longitudinal changes in blood pressure are lacking.

Method:

We evaluated associations of arsenic exposure in relation to longitudinal change in blood pressure in 10,853 participants in the Health Effects of Arsenic Longitudinal Study (HEALS). Arsenic was measured in well water and in urine samples at baseline and in urine samples every 2 years after baseline. Mixed-effect models were used to estimate the association of baseline well and urinary creatinine-adjusted arsenic with annual change in blood pressure …

Prevalence Of And Risk Factors For Intracranial Abnormalities In Unprovoked Seizures., Peter S. Dayan, Kathleen Lillis, Jonathan Bennett, Gregory P. Conners, Pam Bailey, James Callahan, Cigdem Akman, Neil Feldstein, Joshua Kriger, W Allen Hauser, Nathan Kuppermann

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: Prospective data are lacking to determine which children might benefit from prompt neuroimaging after unprovoked seizures. We aimed to determine the prevalence of, and risk factors for, relevant intracranial abnormalities in children with first, unprovoked seizures.

METHODS: We conducted a 6-center prospective study in children aged >28 days to 18 years with seemingly unprovoked seizures. Emergency department (ED) clinicians documented clinical findings on a standardized form. Our main outcome was the presence of a clinically relevant intracranial abnormality on computed tomography (CT) or MRI, defined as those that might change management, either emergently, urgently, or nonurgently.

RESULTS: …

Effects Of A Clinician Referral And Exercise Program For Men Who Have Completed Active Treatment For Prostate Cancer: A Multicenter Cluster Randomized Controlled Trial (Engage)., Patricia M. Livingston, Melinda J. Craike, Jo Salmon, Kerry S. Courneya, Cadeyrn J. Gaskin, Steve F. Fraser, Mohammadreza Mohebbi, Suzanne Broadbent, Mari Botti, Bridie Kent, Engage Uro-Oncology Clinicians' Group

School of Nursing and Midwifery

BACKGROUND: The purpose of this study was to determine the efficacy of a clinician referral and exercise program in improving exercise levels and quality of life for men with prostate cancer. METHODS: This was a multicenter cluster randomized controlled trial in Melbourne, Australia comprising 15 clinicians: 8 clinicians were randomized to refer eligible participants (n = 54) to a 12-week exercise program comprising 2 supervised gym sessions and 1 home-based session per week, and 7 clinicians were randomized to follow usual care (n = 93). The primary outcome was self-reported physical activity; the secondary outcomes were quality of life, anxiety, …

Age At Onset In Patients With Medically Refractory Temporal Lobe Epilepsy And Mesial Temporal Sclerosis: Impact On Clinical Manifestations And Postsurgical Outcome., Ali Akbar Asadi-Pooya, Michael R. Sperling

Department of Neurology Faculty Papers

PURPOSE: To evaluate the demographic and clinical manifestations and postsurgical outcome of childhood-onset mesial temporal sclerosis and temporal lobe epilepsy (MTS-TLE) and establishing the potential differences as compared to the patients with adult-onset MTS-TLE.

METHOD: In this retrospective study all patients with a clinical diagnosis of medically refractory TLE due to mesial temporal sclerosis, who underwent epilepsy surgery at Jefferson comprehensive epilepsy center, were recruited. Patients were prospectively registered in a database from 1986 through 2014. Postsurgical outcome was classified into two groups; seizure-free or relapsed. Clinical manifestations and outcome were compared between patients with childhood-onset MTS-TLE (i.e., age at …

Numerical Chromosomal Instability Mediates Susceptibility To Radiation Treatment, Samuel F. Bakhoum, Lilian Kabeche, Matthew D. Wood, Christopher D. Laucius

Dartmouth Scholarship

The exquisite sensitivity of mitotic cancer cells to ionizing radiation (IR) underlies an important rationale for the widely used fractionated radiation therapy. However, the mechanism for this cell cycle-dependent vulnerability is unknown. Here we show that treatment with IR leads to mitotic chromosome segregation errors in vivo and long-lasting aneuploidy in tumour-derived cell lines. These mitotic errors generate an abundance of micronuclei that predispose chromosomes to subsequent catastrophic pulverization thereby independently amplifying radiation-induced genome damage. Experimentally suppressing whole-chromosome missegregation reduces downstream chromosomal defects and significantly increases the viability of irradiated mitotic cells. Further, orthotopically transplanted human glioblastoma tumours in which …

Genome-Wide Meta-Analysis In Alopecia Areata Resolves Hla Associations And Reveals Two New Susceptibility Loci, Regina C. Betz, Lynn Petukhova, Stephan Ripke, Hailiang Huang, Androniki Menelaou, Silke Redeler, Tim Becker, Stefanie Heilmann, Tarek Yamany, Madeleine Duvic, Maria Hordinsky, David Norris, Vera H. Price, Julian Mackay-Wiggan, Annemieke De Jong, Gina M. Destefano, Susanne Moebus, Markus Böhm, Ulrike Blume-Peytavi, Hans Wolff, Gerhard Lutz, Roland Kruse, Li Bian, Christopher I. Amos

Dartmouth Scholarship

Alopecia areata (AA) is a prevalent autoimmune disease with ten known susceptibility loci. Here we perform the first meta-analysis in AA by combining data from two genome-wide association studies (GWAS), and replication with supplemented ImmunoChip data for a total of 3,253 cases and 7,543 controls. The strongest region of association is the MHC, where we fine-map 4 independent effects, all implicating HLA-DR as a key etiologic driver. Outside the MHC, we identify two novel loci that exceed statistical significance, containing ACOXL/BCL2L11(BIM) (2q13); GARP (LRRC32) (11q13.5), as well as a third nominally significant region SH2B3(LNK)/ ATXN2 (12q24.12). Candidate susceptibility gene expression …

Efficacy Of Galactose And Adalimumab In Patients With Resistant Focal Segmental Glomerulosclerosis: Report Of The Font Clinical Trial Group., Howard Trachtman, Suzanne Vento, Emily Herreshoff, Milena Radeva, Jennifer Gassman, Daniel T. Stein, Virginia J. Savin, Mukut Sharma, Jochen Reiser, Changli Wei, Michael Somers, Tarak Srivastava, Debbie S. Gipson

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Patients with resistant focal segmental glomerulosclerosis (FSGS) who are unresponsive to corticosteroids and other immunosuppressive agents are at very high risk of progression to end stage kidney disease. In the absence of curative treatment, current therapy centers on renoprotective interventions that reduce proteinuria and fibrosis. The FONT (Novel Therapies for Resistant FSGS) Phase II clinical trial (NCT00814255, Registration date December 22, 2008) was designed to assess the efficacy of adalimumab and galactose compared to standard medical therapy which was comprised of lisinopril, losartan, and atorvastatin.

METHODS: Key eligibility criteria were biopsy confirmed primary FSGS or documentation of a causative …

Consumption Of Sutherlandia Frutescens By Hiv-Seropositive South African Adults: An Adaptive Double-Blind Randomized Placebo Controlled Trial., Douglas Wilson, Kathy Goggin, Karen Williams, Mary M. Gerkovich, Nceba Gqaleni, James Syce, Patricia Bartman, Quinton Johnson, William R. Folk

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Sutherlandia frutescens (L.) R. Br. is widely used as an over the counter complementary medicine and in traditional medications by HIV seropositive adults living in South Africa; however the plant's safety has not been objectively studied. An adaptive two-stage randomized double-blind placebo controlled study was used to evaluate the safety of consuming dried S. frutescens by HIV seropositive adults with CD4 T-lymphocyte count of >350 cells/μL.

METHODS: In Stage 1 56 participants were randomized to S. frutescens 400, 800 or 1,200 mg twice daily or matching placebo for 24 weeks. In Stage 2 77 additional participants were randomized to …

A Trimodality Approach In The Management Of Metastatic Low-Grade Epithelioid Hemangioendothelioma Of The Bone, Abhijit Saste, Diego F. Cabrera-Fernandez, Rohit Gulati, Steven Gamalski

Hematology/Oncology Articles

A 29-year-old man presented with a 2-week history of severe pain in the left foot with no preceding history of trauma. A left foot radiograph demonstrated a cortical lucency in the mid-distal shaft of the third metatarsal bone. MRI of the left foot showed an expansile lesion in the same location. A staging bone scan showed a focal uptake in the known lucency in the left third metatarsal and in the proximal left femur. A subsequent left hip radiograph demonstrated a lucency in the intertrochanteric region. CT scan of the chest, abdomen and pelvis was unremarkable. A biopsy of the …

Sex Differences In Clinical Features Of Early, Treated Parkinson's Disease, Erika F. Augustine, Adriana Pérez, Rohit Dhall, Chizoba C. Umeh, Aleksandar Videnovic, Franca Cambi, Anne-Marie A. Wills, Jordan J. Elm, Richard M. Zweig, Lisa M. Shulman, Martha A. Nance, Jacquelyn Bainbridge, Oksana Suchowersky

Neurology Faculty Publications

INTRODUCTION: To improve our understanding of sex differences in the clinical characteristics of Parkinson's Disease, we sought to examine differences in the clinical features and disease severity of men and women with early treated Parkinson's Disease (PD) enrolled in a large-scale clinical trial.

METHODS: Analysis was performed of baseline data from the National Institutes of Health Exploratory Trials in Parkinson's Disease (NET-PD) Long-term Study-1, a randomized, multi-center, double-blind, placebo-controlled study of 10 grams of oral creatine/day in individuals with early, treated PD. We compared mean age at symptom onset, age at PD diagnosis, and age at randomization between …

Dna-Pkcs-Mediated Transcriptional Regulation Drives Prostate Cancer Progression And Metastasis., Jonathan F Goodwin, Vishal Kothari, Justin M Drake, Shuang Zhao, Emanuela Dylgjeri, Jeffry L. Dean, Matthew J. Schiewer, Christopher Mcnair, Jennifer K. Jones, Alvaro Aytes, Michael S. Magee, Adam E. Snook, Ziqi Zhu, Robert Den, Ruth C. Birbe, Leonard G. Gomella, Nicholas A. Graham, Ajay A. Vashisht, James A. Wohlschlegel, Thomas G. Graeber, R. Jeffrey Karnes, Mandeep Takhar, Elai Davicioni, Scott A. Tomlins, Cory Abate-Shen, Nima Sharifi, Owen N. Witte, Felix Y. Feng, Karen E. Knudsen

Department of Cancer Biology Faculty Papers

Emerging evidence demonstrates that the DNA repair kinase DNA-PKcs exerts divergent roles in transcriptional regulation of unsolved consequence. Here, in vitro and in vivo interrogation demonstrate that DNA-PKcs functions as a selective modulator of transcriptional networks that induce cell migration, invasion, and metastasis. Accordingly, suppression of DNA-PKcs inhibits tumor metastases. Clinical assessment revealed that DNA-PKcs is significantly elevated in advanced disease and independently predicts for metastases, recurrence, and reduced overall survival. Further investigation demonstrated that DNA-PKcs in advanced tumors is highly activated, independent of DNA damage indicators. Combined, these findings reveal unexpected DNA-PKcs functions, identify DNA-PKcs as a potent driver …

A Randomized Controlled Trial Of Exercise In Spinal And Bulbar Muscular Atrophy., Joseph A Shrader, Ilona Kats, Angela Kokkinis, Cris Zampieri, Ellen Levy, Galen O Joe, Joshua G. Woolstenhulme, Bart E Drinkard, Michaele R Smith, Willie Ching, Laboni Ghosh, Derrick Fox, Sungyoung Auh, Alice B Schindler, Kenneth H Fischbeck, Christopher Grunseich

Physical Therapy and Health Care Sciences Faculty Publications

OBJECTIVE: To determine the safety and efficacy of a home-based functional exercise program in spinal and bulbar muscular atrophy (SBMA).

METHODS: Subjects were randomly assigned to participate in 12 weeks of either functional exercises (intervention) or a stretching program (control) at the National Institutes of Health in Bethesda, MD. A total of 54 subjects enrolled, and 50 completed the study with 24 in the functional exercise group and 26 in the stretching control group. The primary outcome measure was the Adult Myopathy Assessment Tool (AMAT) total score, and secondary measures included total activity by accelerometry, muscle strength, balance, timed up …

Ketamine For The Treatment Of Depression In Patients Receiving Hospice Care: A Retrospective Medical Record Review Of Thirty-One Cases., Alana Iglewicz, Katherine Morrison, Richard A. Nelesen, Tingting Zhan, Boris Iglewicz, Nathan Fairman, Jeremy M. Hirst, Scott A. Irwin

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Depression is prevalent in patients receiving hospice care. Standard antidepressant medications do not work rapidly enough in this setting. Evidence suggests that ketamine rapidly treats treatment refractory depression in the general population. Ketamine׳s role for treating depression in the hospice population warrants further study.

METHODS: A retrospective medical record review of 31 inpatients receiving hospice care who received ketamine for depression on a clinical basis was conducted. The primary outcome measure was the Clinical Global Impression Scale, which was used retrospectively to rate subjects׳ therapeutic improvement, global improvement, and side effects from ketamine over 21 days. Additionally, time to …

Beta-Blocker Use And 30-Day All-Cause Readmission In Medicare Beneficiaries With Systolic Heart Failure, Vikas Bhatia, Kumar Sanam, Taimoor Hashim, Prakash Deedwania, Wilbert S. Aronow, Ross Fletcher, Ali Ahmed

NYMC Faculty Publications

BACKGROUND: Beta-blockers improve outcomes in patients with systolic heart failure. However, it is unknown whether their initial negative inotropic effect may increase 30-day all-cause readmission, a target outcome for Medicare cost reduction and financial penalty for hospitals under the Affordable Care Act.

METHODS: Of the 3067 Medicare beneficiaries discharged alive from 106 Alabama hospitals (1998-2001) with a primary discharge diagnosis of heart failure and ejection fraction

RESULTS: Beta-blocker use was not associated with 30-day all-cause readmission (hazard ratio [HR] 0.87; 95% confidence interval [CI], 0.64-1.18) or heart failure readmission (HR 0.95; 95% CI, 0.57-1.58), but was significantly associated with lower …

Placental Dna Methylation Related To Both Infant Toenail Mercury And Adverse Neurobehavioral Outcomes, Jennifer Zeynab Joukhadar Maccani, Devin C. Koestler, Barry Lester, E Andres Houseman, David A. Armstrong, Karl T. Kelsey, Carmen J. Marsit

Dartmouth Scholarship

Background:

Prenatal mercury (Hg) exposure is associated with adverse child neurobehavioral outcomes. Because Hg can interfere with placental functioning and cross the placenta to target the fetal brain, prenatal Hg exposure can inhibit fetal growth and development directly and indirectly.

Objectives:

We examined potential associations between prenatal Hg exposure assessed through infant toenail Hg, placental DNA methylation changes, and newborn neurobehavioral outcomes.

Methods:

The methylation status of > 485,000 CpG loci was interrogated in 192 placental samples using Illumina’s Infinium HumanMethylation450 BeadArray. Hg concentrations were analyzed in toenail clippings from a subset of 41 infants; neurobehavior was assessed using the NICU …

Treatment Of Severe Metabolic Alkalosis With Continuous Renal Replacement Therapy: Bicarbonate Kinetic Equations Of Clinical Value, Lenar Yessayan, Jerry Yee, Stan Frinak, David Kwon, Balazs Szamosfalvi

Nephrology Articles

Concomitant severe metabolic alkalosis, hypernatremia, and kidney failure pose a therapeutic challenge. Hemodialysis to correct azotemia and abnormal electrolytes results in rapid correction of serum sodium, bicarbonate, and urea but presents a risk for dialysis disequilibrium and brain edema. We describe a patient with Zollinger-Ellison syndrome with persistent encephalopathy, severe metabolic alkalosis (highest bicarbonate 81 mEq/L), hypernatremia (sodium 157 mEq/L), and kidney failure despite 30 hours of intravenous crystalloids and proton pump inhibitor. We used continuous renal replacement therapy (RRT) with delivered hourly urea clearance of ~3 L/hour (24 hour sustained low efficiency dialysis with regional citrate anticoagulation protocol at …

Risk Analysis Of Prostate Cancer In Practical, A Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci., Ali Amin Al Olama, Sara Benlloch, Antonis C Antoniou, Graham G Giles, Gianluca Severi, David E Neal, Freddie C Hamdy, Jenny L Donovan, Kenneth Muir, Johanna Schleutker, Brian E Henderson, Christopher Haiman, Fredrick R Schumacher, Nora Pashayan, Paul D P Pharoah, Elaine A Ostrander, Janet L Stanford, Jyotsna Batra, Judith A Clements, Suzanne K Chambers, Maren Weischer, Børge G Nordestgaard, Sue A Ingles, Karina D Sorensen, Torben F Orntoft, Jong Y Park, Cezary Cybulski, Christiane Maier, Thilo Doerk, Joanne L Dickinson, Lisa Cannon-Albright, Hermann Brenner, Timothy R Rebbeck, Charnita Zeigler-Johnson, Tomonori Habuchi, Stephen N Thibodeau, Kathleen A Cooney, Pierre O Chappuis, Pierre Hutter, Radka P Kaneva, William D Foulkes, Maurice P Zeegers, Yong-Jie Lu, Hong-Wei Zhang, Robert Stephenson, Angela Cox, Melissa C Southey, Amanda B Spurdle, Liesel Fitzgerald, Daniel Leongamornlert, Edward Saunders, Malgorzata Tymrakiewicz, Michelle Guy, Tokhir Dadaev, Sarah J Little, Koveela Govindasami, Emma Sawyer, Rosemary Wilkinson, Kathleen Herkommer, John L Hopper, Aritaya Lophatonanon, Antje E Rinckleb, Zsofia Kote-Jarai, Rosalind A Eeles, Douglas F Easton

Department of Medical Oncology Faculty Papers

BACKGROUND: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer.

METHODS: We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history.

RESULTS: The prostate cancer risk for men in the top 1% of the …

Hla-Dqa1 And Plcg2 Are Candidate Risk Loci For Childhood-Onset Steroid-Sensitive Nephrotic Syndrome., Rasheed A. Gbadegesin, Adebowale Adeyemo, Nicholas J A Webb, Larry A A. Greenbaum, Asiri Abeyagunawardena, Shenal Thalgahagoda, Arundhati Kale, Debbie Gipson, Tarak Srivastava, Jen-Jar Lin, Deepa Chand, Tracy E. Hunley, Patrick D. Brophy, Arvind Bagga, Aditi Sinha, Michelle N. Rheault, Joanna Ghali, Kathy Nicholls, Elizabeth Abraham, Halima S. Janjua, Abiodun Omoloja, Gina-Marie Barletta, Yi Cai, David D. Milford, Catherine O'Brien, Atif Awan, Vladimir Belostotsky, William E. Smoyer, Alison Homstad, Gentzon Hall, Guanghong Wu, Shashi Nagaraj, Delbert Wigfall, John Foreman, Michelle P. Winn, Mid-West Pediatric Nephrology Consortium

Manuscripts, Articles, Book Chapters and Other Papers

Steroid-sensitive nephrotic syndrome (SSNS) accounts for >80% of cases of nephrotic syndrome in childhood. However, the etiology and pathogenesis of SSNS remain obscure. Hypothesizing that coding variation may underlie SSNS risk, we conducted an exome array association study of SSNS. We enrolled a discovery set of 363 persons (214 South Asian children with SSNS and 149 controls) and genotyped them using the Illumina HumanExome Beadchip. Four common single nucleotide polymorphisms (SNPs) in HLA-DQA1 and HLA-DQB1 (rs1129740, rs9273349, rs1071630, and rs1140343) were significantly associated with SSNS at or near the Bonferroni-adjusted P value for the number of single variants that were …

Long-Term Oncological Outcomes Of A Phase Ii Trial Of Neoadjuvant Chemohormonal Therapy Followed By Radical Prostatectomy For Patients With Clinically Localised, High-Risk Prostate Cancer., Jonathan L. Silberstein, Stephen A. Poon, Daniel D. Sjoberg, Alexandra C. Maschino, Andrew J. Vickers, Aaron Bernie, Badrinath R. Konety, William Kevin Kelly, James A. Eastham

Department of Urology Faculty Papers

OBJECTIVE: To determine long-term oncological outcomes of radical prostatectomy (RP) after neoadjuvant chemohormonal therapy (CHT) for clinically localised, high-risk prostate cancer.

PATIENTS AND METHODS: In this phase II multicentre trial of patients with high-risk prostate cancer (PSA level >20 ng/mL, Gleason ≥8, or clinical stage ≥T3), androgen-deprivation therapy (goserelin acetate depot) and paclitaxel, carboplatin and estramustine were administered before RP. We report the long-term oncological outcomes of these patients and compared them to a contemporary cohort who met oncological inclusion criteria but received RP only.

RESULTS: In all, 34 patients were enrolled and followed for a median of 13.1 years. …

Obesity Early In Adulthood Increases Risk But Does Not Affect Outcomes Of Hepatocellular Carcinoma, Manal M. Hassan, Reham Abdel-Wahab, Ahmed Kaseb, Ahmed Shalaby, Alexandria Phan, Hashem El-Serag, Ernest Hawk, Jeff Morris, Kanwal Pratap Singh Raghav, Ju-Seog Lee, Jean-Nicolas Vauthey, Gehan Bortus, Harrys Torres, Christopher Amos, Robert Wolff, Donghui Li

Dartmouth Scholarship

Despite the significant association between obesity and several cancers, it has been difficult to establish an association between obesity and hepatocellular carcinoma (HCC). Patients with HCC often have ascites, making it a challenge to accurately determine body mass index (BMI), and many factors contribute to the development of HCC. We performed a case–control study to investigate whether obesity early in adulthood affects risk, age of onset, or outcomes of patients with HCC.

Telemetric Blood Pressure Assessment In Angiotensin Ii-Infused Apoe-/- Mice: 28 Day Natural History And Comparison To Tail-Cuff Measurements, Christopher M. Haggerty, Andrea C. Mattingly, Ming C. Gong, Wen Su, Alan Daugherty, Brandon K. Fornwalt

Saha Cardiovascular Research Center Faculty Publications

Abdominal aortic aneurysm (AAA) is a disease of the aortic wall, which can progress to catastrophic rupture. Assessment of mechanical characteristics of AAA, such as aortic distensibility, may provide important insights to help identify at-risk patients and understand disease progression. While the majority of studies on this topic have focused on retrospective patient data, recent studies have used mouse models of AAA to prospectively evaluate the evolution of aortic mechanics. Quantification of aortic distensibility requires accurate measurement of arterial blood pressure, particularly pulse pressure, which is challenging to perform accurately in murine models. We hypothesized that volume/pressure tail-cuff measurements of …

Space Environmental Factor Impacts Upon Murine Colon Microbiota And Mucosal Homeostasis, Lauren E. Ritchie, Stella S. Taddeo, Brad R. Weeks, Florence Lima, Susan A. Bloomfield, M. Andrea Azcarate-Peril, Sara R. Zwart, Scott M. Smith, Nancy D. Turner

Internal Medicine Faculty Publications

Astronaut intestinal health may be impacted by microgravity, radiation, and diet. The aim of this study was to characterize how high and low linear energy transfer (LET) radiation, microgravity, and elevated dietary iron affect colon microbiota (determined by 16S rDNA pyrosequencing) and colon function. Three independent experiments were conducted to achieve these goals: 1) fractionated low LET γ radiation (¹³⁷Cs, 3 Gy, RAD), high Fe diet (IRON) (650 mg/kg diet), and a combination of low LET γ radiation and high Fe diet (IRON+RAD) in male Sprague-Dawley rats; 2) high LET ³⁸Si particle exposure (0.050 Gy), 1/6 G …

Transaction Cost Analysis Of In-Clinic Versus Telehealth Consultations For Chronic Pain: Preliminary Evidence For Rapid And Affordable Access To Interdisciplinary Collaborative Consultation, Brian R. Theodore, Jan Whittington, Cara Towle, David J. Tauben, Barbara Endicott-Popovsky, Alex Cahana, Ardith Z. Doorenbos

Project ECHO Bibliography

OBJECTIVES: With ever increasing mandates to reduce costs and increase the quality of pain management, health care institutions are faced with the challenge of adopting innovative technologies and shifting workflows to provide value-based care. Transaction cost economic analysis can provide comparative evaluation of the consequences of these changes in the delivery of care. The aim of this study was to establish proof-of-concept using transaction cost analysis to examine chronic pain management in-clinic and through telehealth.

METHODS: Participating health care providers were asked to identify and describe two comparable completed transactions for patients with chronic pain: one consultation between patient and …

Genome-Wide Association Study And Admixture Mapping Reveal New Loci Associated With Total Ige Levels In Latinos, Maria Pino-Yanes, Christopher R. Gignoux, Joshua M. Galanter, Albert M. Levin, Catarina D. Campbell, Celeste Eng, Scott Huntsman, Katherine K. Nishimura, Pierre-Antoine Gourraud, Kiana Mohajeri, Brian O'Roak, Donglei Hu, Rasika A. Mathias, Elizabeth A. Nguyen, Lindsey A. Roth, Badri Padhukasahasram, Andres Moreno-Estrada, Karla Sandoval, Cheryl A. Winkler, Fred Lurmann, Adam Davis, Harold J. Farber, Kelley Meade, Pedro C. Avila, Denise Serebrisky, Rocio Chapela, Jean G. Ford, Michael A. Lenoir, Shannon M. Thyne, Emerita Brigino-Buenaventura, Luisa N. Borrell, William Rodriguez-Cintron, Saunak Sen, Rajesh Kumar, Jose R. Rodriguez-Santana, Carlos D. Bustamante, Fernando D. Martinez, Benjamin A. Raby, Scott T. Weiss, Dan L. Nicolae, Carole Ober, Deborah A. Meyers, Eugene R. Bleecker, Steven J. Mack, Ryan D. Hernandez, Evan E. Eichler, Kathleen C. Barnes, Keoki L. Williams, Dara G. Torgerson, Esteban G. Burchard

Center for Health Policy and Health Services Research Articles

BACKGROUND: IgE is a key mediator of allergic inflammation, and its levels are frequently increased in patients with allergic disorders.

OBJECTIVE: We sought to identify genetic variants associated with IgE levels in Latinos.

METHODS: We performed a genome-wide association study and admixture mapping of total IgE levels in 3334 Latinos from the Genes-environments & Admixture in Latino Americans (GALA II) study. Replication was evaluated in 454 Latinos, 1564 European Americans, and 3187 African Americans from independent studies.

RESULTS: We confirmed associations of 6 genes identified by means of previous genome-wide association studies and identified a novel genome-wide significant association of …

Quantifying Unnecessary Normal Tissue Complication Risks Due To Suboptimal Planning: A Secondary Study Of Rtog 0126., Kevin L. Moore, Rachel Schmidt, Vitali Moiseenko, Lindsey A. Olsen, Jun Tan, Ying Xiao, James Galvin, Stephanie Pugh, Michael J Seider, Adam P. Dicker, Walter Bosch, Jeff Michalski, Sasa Mutic

Department of Radiation Oncology Faculty Papers

PURPOSE: The purpose of this study was to quantify the frequency and clinical severity of quality deficiencies in intensity modulated radiation therapy (IMRT) planning in the Radiation Therapy Oncology Group 0126 protocol.

METHODS AND MATERIALS: A total of 219 IMRT patients from the high-dose arm (79.2 Gy) of RTOG 0126 were analyzed. To quantify plan quality, we used established knowledge-based methods for patient-specific dose-volume histogram (DVH) prediction of organs at risk and a Lyman-Kutcher-Burman (LKB) model for grade ≥2 rectal complications to convert DVHs into normal tissue complication probabilities (NTCPs). The LKB model was validated by fitting dose-response parameters relative …

Prophylactic Methylprednisolone To Reduce Inflammation And Improve Outcomes From One Lung Ventilation In Children: A Randomized Clinical Trial., Mary C. Theroux, Alicia Olivant Fisher, Maria E. Rodriguez, Robert P. Brislin, Kirk W. Reichard, Suken A. Shah, Matt Mccoy, Melinda Brown, Kirk W. Dabney, William G. Mackenzie, Douglas A. Katz, Thomas H. Shaffer

Department of Anesthesiology Faculty Papers

BACKGROUND: One lung ventilation (OLV) results in inflammatory and mechanical injury, leading to intraoperative and postoperative complications in children. No interventions have been studied in children to minimize such injury.

OBJECTIVE: We hypothesized that a single 2-mg·kg(-1) dose of methylprednisolone given 45-60 min prior to lung collapse would minimize injury from OLV and improve physiological stability.

METHODS: Twenty-eight children scheduled to undergo OLV were randomly assigned to receive 2 mg·kg(-1) methylprednisolone (MP) or normal saline (placebo group) prior to OLV. Anesthetic management was standardized, and data were collected for physiological stability (bronchospasm, respiratory resistance, and compliance). Plasma was assayed for …

Integrated Psychological Care In Head And Neck Cancer: Views From Health Care Providers, Patients, And Supports, Michelle T. Jesse, Michael Ryan, Anne Eshelman, Tamer Ghanem, Amy M. Williams, Lisa R. Miller-Matero, Kathleen Yaremchuk

Otolaryngology Articles

OBJECTIVES/HYPOTHESIS: An evaluation by head-and-neck cancer (HNC) staff, patients, and patient support feedback regarding integrated psychological care and perceived benefit based on patient characteristics.

STUDY DESIGN: Cross-sectional survey of HNC staff, patients, and their primary supports; and retrospective chart review of psychiatric characteristics of HNC patients.

METHODS: HNC staff, patients (who were evaluated by the integrated psychologist), and their primary supports were given questionnaires on their perception of benefit of including a psychologist in the evaluation and treatment of HNC patients. Also, a retrospective chart review on patients who were psychiatrically evaluated by the psychologist on sociodemographics and psychiatric characteristics. …

Identification Of Novel Genes That Regulate Androgen Receptor Signaling And Growth Of Androgen-Deprived Prostate Cancer Cells, Elina Levina, Hao Ji, Mengqiang Chen, Mirza Baig, David Oliver, Patrice Ohouo, Chang-Uk Lim, Garry Schools, Steven Carmack, Ye Ding, Eugenia Broude, Igor Roninson, Ralph Buttyan, Michael Shtutman

Faculty Publications

Prostate cancer progression to castration refractory disease is associated with anomalous transcriptional activity of the androgen receptor (AR) in an androgen-depleted milieu. To identify novel gene products whose downregulation transactivates AR in prostate cancer cells, we performed a screen of enzymatically-generated shRNA lenti-libraries selecting for transduced LNCaP cells with elevated expression of a fluorescent reporter gene under the control of an AR-responsive promoter. The shRNAs present in selected populations were analyzed using high-throughput sequencing to identify target genes. Highly enriched gene targets were then validated with siRNAs against selected genes, testing first for increased expression of luciferase from an AR-responsive …

Disease-Related Microglia Heterogeneity In The Hippocampus Of Alzheimer's Disease, Dementia With Lewy Bodies, And Hippocampal Sclerosis Of Aging, Adam D. Bachstetter, Linda J. Van Eldik, Frederick A. Schmitt, Janna H. Neltner, Eseosa T. Ighodaro, Scott J. Webster, Ela Patel, Erin L. Abner, Richard J. Kryscio, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Introduction: Neuropathological, genetic, and biochemical studies have provided support for the hypothesis that microglia participate in Alzheimer's disease (AD) pathogenesis. Despite the extensive characterization of AD microglia, there are still many unanswered questions, and little is known about microglial morphology in other common forms of age-related dementia: particularly, dementia with Lewy bodies (DLB) and hippocampal sclerosis of aging (HS-Aging). In addition, no prior studies have attempted to compare and contrast the microglia morphology in the hippocampus of various neurodegenerative conditions.

Results: Here we studied cases with pathologically-confirmed AD (n = 7), HS-Aging (n = 7), AD + HS-aging …