Digital Commons Network^™

Family Factors That Characterize Adolescents With Severe Obesity And Their Role In Weight Loss Surgery Outcomes., Meg H. Zeller, Sanita Hunsaker, Carmen Mikhail, Jennifer Reiter-Purtill, Mary Beth Mccullough, Beth Garland, Heather Austin, Gia Washington, Amy Baughcum, Dana Rofey, Kevin Smith, Teenview Study Group And In Collaboration With The Teen-Labs Consortium

Manuscripts, Articles, Book Chapters and Other Papers

Objective: To comprehensively assess family characteristics of adolescents with severe obesity and whether family factors impact weight loss outcomes following weight loss surgery (WLS).

Methods: Multisite prospective data from 138 adolescents undergoing WLS and primary caregivers (adolescent: Mage = 16.9; MBMI = 51.5 kg/m2 ; caregiver: Mage = 44.5; 93% female) and 83 nonsurgical comparators (NSComp: adolescent: Mage = 16.1; MBMI = 46.9 kg/m2 ; caregiver: Mage = 43.9; 94% female) were collected using standardized measures at presurgery/baseline and at 1 and 2 years.

Results: The majority (77.3%) of caregivers had obesity, with rates of caregiver WLS significantly higher in …

A Trial Of Unrelated Donor Marrow Transplantation For Children With Severe Sickle Cell Disease., Shalini Shenoy, Mary Eapen, Julie A. Panepinto, Brent R. Logan, Juan Wu, Allistair Abraham, Joel Brochstein, Sonali Chaudhury, Kamar Godder, Ann E. Haight, Kimberly A. Kasow, Kathryn Leung, Martin Andreansky, Monica Bhatia, Jignesh Dalal, Hilary Haines, Jennifer Jaroscak, Hillard M. Lazarus, John E. Levine, Lakshmanan Krishnamurti, David Margolis, Gail C. Megason, Lolie C. Yu, Michael A. Pulsipher, Iris Gersten, Nancy Difronzo, Mary M. Horowitz, Mark C. Walters, Naynesh Kamani

Manuscripts, Articles, Book Chapters and Other Papers

Children with sickle cell disease experience organ damage, impaired quality of life, and premature mortality. Allogeneic bone marrow transplant from an HLA-matched sibling can halt disease progression but is limited by donor availability. A Blood and Marrow Transplant Clinical Trials Network (BMT CTN) phase 2 trial conducted from 2008 to 2014 enrolled 30 children aged 4 to 19 years; 29 were eligible for evaluation. The primary objective was 1-year event-free survival (EFS) after HLA allele-matched (at HLA-A, -B, -C, and -DRB1 loci) unrelated donor transplant. The conditioning regimen included alemtuzumab, fludarabine, and melphalan. Graft-versus-host disease (GVHD) prophylaxis included calcineurin inhibitor, …

Correlates Of Sexual-Risk Behaviors Among Young Black Msm: Implications For Clinic-Based Counseling Programs, Richard A. Crosby, Leandro Mena, Janelle M. Ricks

Health, Behavior & Society Faculty Publications

This study applied an 8-item index of recent sexual-risk behaviors to young Black men who have sex with men (YBMSM) and evaluated the distribution for normality. The distribution was tested for associations with possible antecedents of sexual risk. YBMSM (N = 600), aged 16–29 years, were recruited from a sexually transmitted infection clinic, located in the southern US. Men completed an extensive audio computer-assisted self-interview. Thirteen possible antecedents of sexual risk, as assessed by the index, were selected for analyses. The 8-item index formed a normal distribution with a mean of 4.77 (SD = 1.77). In adjusted analyses, not …

Functional Validation Of Novel Compound Heterozygous Variants In B3gat3 Resulting In Severe Osteopenia And Fractures: Expanding The Disease Phenotype., Florian Job, Shuji Mizumoto, Laurie Smith, Natario Couser, Ashley Brazil, Howard Saal, Melanie Patterson, Margaret Gibson, Sarah E. Soden, Neil A. Miller, Isabelle Thiffault, Carol J. Saunders, Shuhei Yamada, Katrin Hoffmann, Kazuyuki Sugahara, Emily G. Farrow

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: A new disease class of syndromes, described as linkeropathies, which are derived from defects in the glycosaminoglycan-linker region as well as glycosaminoglycan-side chains of proteoglycans is increasingly being recognized as a cause of human disease. Proteoglycans are an essential component of the extracellular matrix. Defects in the enzymatic process of proteoglycan synthesis broadly occur due to the incorrect addition of side chains. Previously, homozygous missense variants within the B3GAT3 gene encoding beta 1,3 glucuronyltransferase 3(GlcAT-I) responsible for the biosynthesis of glycosaminoglycans have been described in 7 individuals.

CASE PRESENTATION: In this study, a 4-year-old patient with a severe phenotype …

Quantitative Proteomic Profiling Reveals Hepatic Lipogenesis And Liver X Receptor Activation In The Pander Transgenic Model., Mark G. Athanason, Whitney A. Ratliff, Dale Chaput, Catherine B. Marelia, Melanie N. Kuehl, Stanley M. Stevens Jr., Brant R. Burkhardt

Molecular Biosciences Faculty Publications

PANcreatic-DERived factor (PANDER) is a member of a superfamily of FAM3 proteins modulating glycemic levels by metabolic regulation of the liver and pancreas. The precise PANDER-induced hepatic signaling mechanism is still being elucidated and has been very complex due to the pleiotropic nature of this novel hormone. Our PANDER transgenic (PANTG) mouse displays a selective hepatic insulin resistant (SHIR) phenotype whereby insulin signaling is blunted yet lipogenesis is increased, a phenomena observed in type 2 diabetes. To examine the complex PANDER-induced mechanism of SHIR, we utilized quantitative mass spectrometry-based proteomic analysis using Stable Isotope Labeling by Amino Acids in Cell …

Relationships Between Digit Ratio (2d:4d) And Basketball Performance In Australian Men, Nathan A. Frick, Melissa J. Hull, John T. Manning, Grant Tomkinson

Education, Health & Behavior Studies Faculty Publications

Objective

To investigate relationships between the digit ratio (2D:4D) and competitive basketball performance in Australian men.

Methods

Using an observational cross‐sectional design a total of 221 Australian basketball players who competed in the Olympic Games, International Basketball Federation World Championships/Cup, Australian National Basketball League, Central Australian Basketball League or socially had their 2D:4Ds measured. Analysis of variance was used to assess differences in mean 2D:4Ds between men playing at different competitive standards, with relationships between 2D:4Ds and basketball game‐related statistics assessed using Pearson's product moment correlations in men playing at a single competitive standard.

Results

There were significant differences between …

The Serotonin Transporter Promoter Polymorphism Moderates The Continuity Of Behavioral Inhibition In Early Childhood., Victoria C Johnson, Katie R Kryski, Haroon I Sheikh, Heather J Smith, Shiva M Singh, Elizabeth P Hayden

Brain and Mind Institute Researchers' Publications

Persistently elevated behavioral inhibition (BI) in children is a marker of vulnerability to psychopathology. However, little research has considered the joint influences of caregiver and child factors that may moderate the continuity of BI in early childhood, particularly genetic variants that may serve as markers of biological plasticity, such as the serotonin transporter linked polymorphic region (5-HTTLPR). We explored this issue in 371 preschoolers and their caregivers, examining whether parent characteristics (i.e., overinvolvement or anxiety disorder) and child 5-HTTLPR influenced the continuity of BI between ages 3 and 5. Measures were observational ratings of child BI, observational and questionnaire measures …

Performance Of A1c Versus Ogtt For The Diagnosis Of Prediabetes In A Community-Based Screening, Jenny E. Camacho, Vallabh O. Shah, Ronald Schrader, Craig S. Wong, Mark R. Burge

Pediatrics Research and Scholarship

OBJECTIVE: Reliable identification of individuals at risk for developing diabetes is critical to instituting preventative strategies. Studies suggest that the accuracy of using hemoglobin A1c as a sole diagnostic criterion for diabetes may be variable across different ethnic groups. We postulate that there will be lack of concordance between A1c and the oral glucose tolerance test (OGTT) for diagnosing prediabetes across Hispanic and non-Hispanic white (NHW) populations.

METHODS: A total of 218 asymptomatic adults at risk for type 2 diabetes (T2D) were assessed with A1c and OGTT for the diagnosis of prediabetes. Glucose homeostasis status was assigned as no diabetes …

Circumcision Status Is Not Associated With Condom Use And Prevalence Of Sexually Transmitted Infections Among Young Black Msm, Richard A. Crosby, Cynthia A. Graham, Leandro Mena, William L. Yarber, Stephanie A. Sanders, Robin R. Milhausen, Angelica Geter

Health, Behavior & Society Faculty Publications

This study investigated whether intact young Black MSM differed from their circumcised counterparts regarding condom use behaviors and perceptions and HIV/Chlamydia/gonorrhea. Young Black MSM completed a self-interview, including a pictorial item assessing circumcision status and measures of condom use. Twenty-seven percent of 388 participants reported not being circumcised. With one exception, no associations tested approached significance. The mean frequency of unprotected insertive anal sex for circumcised men was about twice as high compared to those intact (P = .04). Intact young Black MSM did not differ from circumcised men relative to prevalence of STIs (including HIV) or condom use behaviors …

Institutional Racism Through The Eyes Of African American Male Faculty At Community Colleges In The Pacific Northwest, Kimberly Harden

CUP Ed.D. Dissertations

The purpose of this qualitative study is to explore the lived experiences of African American male faculty at community colleges in the Pacific Northwest. Regional data mirrors national statistics denoting the low number of faculty of color working at state-funded community colleges. The literature reviewed for this study suggests that African American male faculty experience racism and gender bias during their academic career journeys. This study sought insight from five African American male faculty to answer the overarching research question: What are the possible perceived institutional barriers that contribute to the underrepresentation of African American male faculty? These individuals were …

Human-Associated Bacteroides Spp. And Human Polyomaviruses As Microbial Source Tracking Markers In Hawaii, Marek Kirs, Roberto A Caffaro-Filho, Mayee Wong, Valerie J. Harwood, Philip Moravcik, Roger S Fujioka

Integrative Biology Faculty and Staff Publications

Identification of sources of fecal contaminants is needed to (i) determine the health risk associated with recreational water use and (ii) implement appropriate management practices to mitigate this risk and protect the environment. This study evaluated human-associated Bacteroides spp. (HF183TaqMan) and human polyomavirus (HPyV) markers for host sensitivity and specificity using human and animal fecal samples collected in Hawaii. The decay rates of those markers and indicator bacteria were identified in marine and freshwater microcosms exposed and not exposed to sunlight, followed by field testing of the usability of the molecular markers. Both markers were strongly associated with sewage, although …

Shorter Remission Telomere Length Predicts Delayed Neutrophil Recovery After Acute Myeloid Leukemia Therapy: A Report From The Children's Oncology Group., Robert B. Gerbing, Todd A. Alonzo, Lillian Sung, Alan S. Gamis, Soheil Meshinchi, Sharon E. Plon, Alison A. Bertuch, Maria M. Gramatges

Manuscripts, Articles, Book Chapters and Other Papers

Purpose Suboptimal outcomes for children with acute myeloid leukemia (AML) necessitate maximally intensive therapy. Consequently, serious adverse events, such as prolonged periods of profound myelosuppression, contribute to AML treatment-related mortality. Telomeres, the repetitive DNA-protein structures at chromosome ends, influence cellular replicative capacity in that critically short telomeres can induce cell senescence or apoptosis. Our objective was to evaluate the impact of telomere length on duration of post-therapy neutropenia in a pediatric AML cohort. Patients and Methods Patients were diagnosed with de novo AML, enrolled in Children's Oncology Group study AAML0531, and included those with (n = 53) and without (n …

Ibd Live Case Series-Case 6., Dhyan Rajan, Julia B. Greer, Miguel D. Regueiro, Leonard Baidoo, David G. Binion, Hans H. Herfarth, Corey A. Siegel, Douglas J. Hartman, Francis A. Farraye, Ioannis E. Koutroubakis, Myron H. Brand, Emmanuelle D. Williams, Alka Goyal, Raymond K. Cross

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Association Between Prolonged Neutropenia And Reduced Relapse Risk In Pediatric Aml: A Report From The Children's Oncology Group., Lillian Sung, Richard Aplenc, Todd A. Alonzo, Robert B. Gerbing, Yi-Cheng Wang, Soheil Meshinchi, A S. Gamis

Manuscripts, Articles, Book Chapters and Other Papers

Objective was to describe the relationship between the number of sterile site infections and duration of neutropenia during the first four cycles of chemotherapy and the risk of recurrence and overall survival in children with newly diagnosed acute myeloid leukemia (AML). AAML0531 was a Children's Oncology Group randomized phase 3 clinical trial that included 1022 children with de novo AML. For this analysis, we focused on non-Down syndrome favorable and standard risk patients who completed at least 4 cycles of chemotherapy without recurrence or withdrawal during protocol therapy. Those receiving hematopoietic stem cell transplantation in first remission were excluded. Five …

Risk Factors For Sleep-Related Infant Deaths In In-Home And Out-Of-Home Settings., Hilina Kassa, Rachel Y. Moon, Jeffrey D. Colvin

Manuscripts, Articles, Book Chapters and Other Papers

Background and objective: Multiple environmental risk factors are associated with sleep-related infant deaths. Little is known about differences in risk factors for deaths occurring in-home and out-of-home. We sought to compare risk factors for in-home and out-of-home infant deaths.

Methods: We conducted a cross-sectional analysis of sleep-related infant deaths from 2004 to 2014 in the National Child Fatality Review and Prevention database. The main exposure was setting (in-home versus out-of-home) at time of death. Primary outcomes were known risk factors: sleep position, sleep location (eg, crib), objects in the environment, and bed sharing. Risk factors for in-home versus out-of-home deaths …

The Influence Of Age On The Diagnostic Performance Of White Blood Cell Count And Absolute Neutrophil Count In Suspected Pediatric Appendicitis., Richard G. Bachur, Peter S. Dayan, Nanette C. Dudley, Lalit Bajaj, Michelle D. Stevenson, Charles G. Macias, Manoj K. Mittal, Jonathan Bennett, Kelly A. Sinclair, Michael C. Monuteaux, Anupam B. Kharbanda

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: White blood cell (WBC) count and absolute neutrophil count (ANC) are a standard part of the evaluation of suspected appendicitis. Specific threshold values are utilized in clinical pathways, but the discriminatory value of WBC count and ANC may vary by age. The objective of this study was to investigate whether the diagnostic value of WBC count and ANC varies across age groups and whether diagnostic thresholds should be age-adjusted.

METHODS: This is a multicenter prospective observational study of patients aged 3-18 years who were evaluated for appendicitis. Receiver operator characteristic curves were developed to assess overall discriminative power of …

Plant Expression Of Cocaine Hydrolase-Fc Fusion Protein For Treatment Of Cocaine Abuse, Guojun Wang, Ting Zhang, Haifeng Huang, Shurong Hou, Xiabin Chen, Fang Zheng, Chang-Guo Zhan

Molecular Modeling and Biopharmaceutical Center Faculty Publications

BACKGROUND: A recently reported cocaine hydrolase (CocH3) fused with fragment crystallizable (Fc) region of human immunoglobulin G1, denoted as CocH3-Fc, is known as a promising therapeutic candidate for the treatment of cocaine overdose and addiction. A challenge for practical therapeutic use of this enzyme exists in the large-scale protein production and, therefore, it is interesting to identify a low-cost and feasible, sustainable source of CocH3-Fc production.

RESULTS: CocH3-Fc was transiently expressed in plant Nicotiana benthamiana leaves. The plant-expressed protein, denoted as pCocH3-Fc, was as active as that expressed in mammalian cells both in vitro and in vivo. However, compared to …

Biallelic Mutations In Tbcd, Encoding The Tubulin Folding Cofactor D, Perturb Microtubule Dynamics And Cause Early-Onset Encephalopathy., Elisabetta Flex, Marcello Niceta, Serena Cecchetti, Isabelle Thiffault, Margaret G. Au, Alessandro Capuano, Emanuela Piermarini, Anna A. Ivanova, Joshua W. Francis, Giovanni Chillemi, Balasubramanian Chandramouli, Giovanna Carpentieri, Charlotte A. Haaxma, Andrea Ciolfi, Simone Pizzi, Ganka V. Douglas, Kara Levine, Antonella Sferra, Maria Lisa Dentici, Rolph R. Pfundt, Jean-Baptist Lepichon, Emily G. Farrow, Frank Baas, Fiorella Piemonte, Bruno Dallapiccola, John M. Graham, Carol J. Saunders, Enrico Bertini, Richard A. Kahn, David A. Koolen, Marco Tartaglia

Manuscripts, Articles, Book Chapters and Other Papers

Microtubules are dynamic cytoskeletal elements coordinating and supporting a variety of neuronal processes, including cell division, migration, polarity, intracellular trafficking, and signal transduction. Mutations in genes encoding tubulins and microtubule-associated proteins are known to cause neurodevelopmental and neurodegenerative disorders. Growing evidence suggests that altered microtubule dynamics may also underlie or contribute to neurodevelopmental disorders and neurodegeneration. We report that biallelic mutations in TBCD, encoding one of the five co-chaperones required for assembly and disassembly of the αβ-tubulin heterodimer, the structural unit of microtubules, cause a disease with neurodevelopmental and neurodegenerative features characterized by early-onset cortical atrophy, secondary hypomyelination, microcephaly, thin …

Throat Swabs And Sputum Culture As Predictors Of P. Aeruginosa Or S. Aureus Lung Colonization In Adult Cystic Fibrosis Patients, Darius Seidler, Mary Griffin, Amanda Nymon, Katja Koeppen, Alix Ashare

Dartmouth Scholarship

Background:

Due to frequent infections in cystic fibrosis (CF) patients, repeated respiratory cultures are obtained to inform treatment. When patients are unable to expectorate sputum, clinicians obtain throat swabs as a surrogate for lower respiratory cultures. There is no clear data in adult subjects demonstrating the adequacy of throat swabs as a surrogate for sputum or BAL. Our study was designed to determine the utility of throat swabs in identifying lung colonization with common organisms in adults with CF.

Methods:

Adult CF subjects (n = 20) underwent bronchoscopy with BAL. Prior to bronchoscopy, a throat swab was obtained. A sputum …

Post-Transplant Outcomes In High-Risk Compared With Non-High-Risk Multiple Myeloma: A Cibmtr Analysis., Emma C. Scott, Parameswaran Hari, Manish Sharma, Jennifer Le-Rademacher, Jiaxing Huang, Dan Vogl, Muneer Abidi, Amer Beitinjaneh, Henry Fung, Siddhartha Ganguly, Gerhard Hildebrandt, Leona Holmberg, Matt Kalaycio, Shaji Kumar, Robert Kyle, Hillard Lazarus, Cindy Lee, Richard T. Maziarz, Kenneth Meehan, Joseph Mikhael, Taiga Nishihori, Muthalagu Ramanathan, Saad Usmani, Jason Tay, David Vesole, Baldeep Wirk, Jean Yared, Bipin N. Savani, Cristina Gasparetto, Amrita Krishnan, Tomer Mark, Yago Nieto, Anita D'Souza

Department of Medical Oncology Faculty Papers

Conventional cytogenetics and interphase fluorescence in situ hybridization (FISH) identify high-risk multiple myeloma (HRM) populations characterized by poor outcomes. We analyzed these differences among HRM versus non-HRM populations after upfront autologous hematopoietic cell transplantation (autoHCT). Between 2008 and 2012, 715 patients with multiple myeloma identified by FISH and/or cytogenetic data with upfront autoHCT were identified in the Center for International Blood and Marrow Transplant Research database. HRM was defined as del17p, t(4;14), t(14;16), hypodiploidy (-Y) or chromosome 1 p and 1q abnormalities; all others were non-HRM. Among 125 HRM patients (17.5%), induction with bortezomib and immunomodulatory agents (imids) was higher …

Increased Peptide Yy Blood Concentrations, Not Decreased Acyl-Ghrelin, Are Associated With Reduced Hunger And Food Intake In Healthy Older Women: Preliminary Evidence., Mary Hickson, Charlotte Moss, Waljit S. Dhillo, Jeanne Bottin, Gary Frost

School of Health Professions

With ageing there is frequently a loss of appetite, termed anorexia of ageing, which can result in under-nutrition. We do not know how appetite control alters with ageing. The objective of this study was to investigate whether differences in the release of, and response to, gastrointestinal appetite hormones is altered in young compared to old healthy volunteers. We hypothesised that an increase in PYY and GLP-1 or a decrease ghrelin may result in a decreased appetite. A comparative experimental design, using a cross-sectional sample of ages from a healthy population, matched for sex and BMI was used. The study compared …

Decreasing Patient Cost And Travel Time Through Pediatric Rheumatology Telemedicine Visits., Elizabeth A. Kessler, Ashley K. Sherman, Mara L. Becker

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: There is a critical shortage of pediatric rheumatologists in the US. Substantial travel to clinics can impose time and monetary burdens on families. The aim of this study was to evaluate the cost of in-person pediatric rheumatology visits for families and determine if telemedicine clinics resulted in time and cost savings. Factors associated with interest in telemedicine were also explored.

METHODS: Surveys were offered to parents and guardians of patients in Pediatric Rheumatology follow-up clinics in Kansas City, Missouri, the primary site of in-person care, and at a telemedicine outreach site 160 miles away, in Joplin, Missouri. Survey questions …

Methodology Of Aa Crash: A Prospective Observational Study Evaluating The Incidence And Pathogenesis Of Adverse Post-Traumatic Sequelae In African-Americans Experiencing Motor Vehicle Collision., Sarah D. Linnstaedt, Jun-Mei Hu, Andrea Y. Liu, April C. Soward, Kenneth A. Bollen, Henry E. Wang, Phyllis L. Hendry, Erin Zimny, Christopher A. Lewandowski, Marc-Anthony Velilla, Kathia Damiron, Claire Pearson, Robert Domeier, Sangeeta Kaushik, James Feldman, Mark Rosenberg, Jeffrey Jones, Robert Swor, Niels Rathlev, Samuel A. Mclean

Emergency Medicine Articles

INTRODUCTION: A motor vehicle collision (MVC) is one of the most common life-threatening events experienced by individuals living in the USA. While most individuals recover following MVC, a significant proportion of individuals develop adverse post-traumatic sequelae such as post-traumatic stress disorder or persistent musculoskeletal pain. Adverse post-traumatic sequelae are common, morbid and costly public health problems in the USA and other industrialised countries. The pathogenesis of these disorders following MVC remains poorly understood. In the USA, available data suggest that African-Americans experience an increased burden of adverse post-traumatic sequelae after MVC compared to European Americans, but to date no studies …

Conditional Ablation Of Hdac3 In Islet Beta Cells Results In Glucose Intolerance And Enhanced Susceptibility To Stz-Induced Diabetes, Wen-Bin Chen, Ling Gao, Jie Wang, Yan-Gang Wang, Zheng Dong, Jiajun Zhao, Qing-Sheng Mi, Li Zhou

Dermatology Articles

Histone deacetylases (HDACs) are enzymes that regulate gene expression by modifying chromatin structure through removal of acetyl groups from target histones or non-histone proteins. Previous in vitro studies suggest that HDACs may be novel pharmacological targets in immune-mediated islet β-cell destruction. However, the role of specific HDAC in islet β-cell development and function remain unclear. Here, we generated a conditional islet β-cells specific HDAC3 deletion mouse model to determine the consequences of HDAC3 depletion on islet β-cell differentiation, maintenance and function. Islet morphology, insulin secretion, glucose tolerance, and multiple low-dose streptozotocin (STZ)-induced diabetes incidence were evaluated and compared between HDAC3 …

The Effects Of Oncologist Implicit Racial Bias In Racially Discordant Oncology Interactions, Louis A. Penner, John F. Dovidio, Richard Gonzalez, Terrance L. Albrecht, Robert Chapman, Tanina Foster, Felicity Wk Harper, Nao Hagiwara, Lauren M. Hamel, Anthony F. Shields, Shirish Gadgeel, Michael S. Simon, Jennifer J. Griggs, Susan Eggly

Hematology/Oncology Articles

PURPOSE: Health providers' implicit racial bias negatively affects communication and patient reactions to many medical interactions. However, its effects on racially discordant oncology interactions are largely unknown. Thus, we examined whether oncologist implicit racial bias has similar effects in oncology interactions. We further investigated whether oncologist implicit bias negatively affects patients' perceptions of recommended treatments (i.e., degree of confidence, expected difficulty). We predicted oncologist implicit bias would negatively affect communication, patient reactions to interactions, and, indirectly, patient perceptions of recommended treatments.

METHODS: Participants were 18 non-black medical oncologists and 112 black patients. Oncologists completed an implicit racial bias measure several …

Adam17 Substrate Release In Proximal Tubule Drives Kidney Fibrosis, Eirini Kefaloyianni, Muthu Lakshmi Muthu, Jakob Kaeppler, Xiaoming Sun, Venkata Sabbisetti, Athena Chalaris, Stefan Rose-John, Eitan Wong, Irit Sagi, Sushrut S. Waikar, Helmut Rennke, Benjamin D. Humphreys, Joseph V. Bonventre, Andreas Herrlich

Open Access Publications

Kidney fibrosis following kidney injury is an unresolved health problem and causes significant morbidity and mortality worldwide. In a study into its molecular mechanism, we identified essential causative features. Acute or chronic kidney injury causes sustained elevation of a disintegrin and metalloprotease 17 (ADAM17); of its cleavage-activated proligand substrates, in particular of pro-TNFα and the EGFR ligand amphiregulin (pro-AREG); and of the substrates' receptors. As a consequence, EGFR is persistently activated and triggers the synthesis and release of proinflammatory and profibrotic factors, resulting in macrophage/neutrophil ingress and fibrosis. ADAM17 hypomorphic mice, specific ADAM17 inhibitor-treated WT mice, or mice with inducible …

Mitochondrial Akt Regulation Of Hypoxic Tumor Reprogramming., Young Chan Chae, Valentina Vaira, M. Cecilia Caino, Hsin-Yao Tang, Jae Ho Seo, Andrew V. Kossenkov, Luisa Ottobrini, Cristina Martelli, Giovanni Lucignani, Irene Bertolini, Marco Locatelli, Kelly G. Bryant, Jagadish C. Ghosh, Sofia Lisanti, Bonsu Ku, Silvano Bosari, Lucia R. Languino, David W. Speicher, Dario C. Altieri

Department of Cancer Biology Faculty Papers

Hypoxia is a universal driver of aggressive tumor behavior, but the underlying mechanisms are not completely understood. Using a phosphoproteomics screen, we now show that active Akt accumulates in the mitochondria during hypoxia and phosphorylates pyruvate dehydrogenase kinase 1 (PDK1) on Thr346 to inactivate the pyruvate dehydrogenase complex. In turn, this pathway switches tumor metabolism toward glycolysis, antagonizes apoptosis and autophagy, dampens oxidative stress, and maintains tumor cell proliferation in the face of severe hypoxia. Mitochondrial Akt-PDK1 signaling correlates with unfavorable prognostic markers and shorter survival in glioma patients and may provide an "actionable" therapeutic target in cancer.

Expanding The Phenotype Associated With Naa10-Related N-Terminal Acetylation Deficiency., Chloé Saunier, Svein Isungset Støve, Bernt Popp, Bénédicte Gérard, Marina Blenski, Nicholas Ahmew, +Several Additional Authors

Pediatrics Faculty Publications

N-terminal acetylation is a common protein modification in eukaryotes associated with numerous cellular processes. Inherited mutations in NAA10, encoding the catalytic subunit of the major N-terminal acetylation complex NatA have been associated with diverse, syndromic X-linked recessive disorders, whereas de novo missense mutations have been reported in one male and one female individual with severe intellectual disability but otherwise unspecific phenotypes. Thus, the full genetic and clinical spectrum of NAA10 deficiency is yet to be delineated. We identified three different novel and one known missense mutation in NAA10, de novo in 11 females, and due to maternal germ …

Elevated Integrin Α6Β4 Expression Is Associated With Venous Invasion And Decreased Overall Survival In Non-Small Cell Lung Cancer, Rachel L. Stewart, Dava West, Chi Wang, Heidi L. Weiss, Tamas S. Gal, Eric B. Durbin, William O'Connor, Min Chen, Kathleen L. O'Connor

Pathology and Laboratory Medicine Faculty Publications

Lung cancer carries a poor prognosis and is the most common cause of cancer-related death worldwide. The integrin α6β4, a laminin receptor, promotes carcinoma progression in part by cooperating with various growth factor receptors to facilitate invasion and metastasis. In carcinoma cells with mutant TP53, the integrin α6β4 promotes cell survival. TP53 mutations and integrin α6β4 overexpression co-occur in many aggressive malignancies. Because of the high frequency of TP53 mutations in lung squamous cell carcinoma (SCC), we sought to investigate the association of integrin β4 expression with clinicopathologic features and survival in non–small cell lung cancer (NSCLC). We constructed …

Developing A Model System To Study The Mechanisms Of Resveratrol Inhibition Of Ar-V7 Transcriptional Activity, Sarah R. Wilson

PCOM Biomedical Studies Student Scholarship

Prostate cancer is one of the biggest threats to men’s health in the western world and it accounts for the second largest number of male cancer-related deaths in the United States. It is well established that prostate cancer cells depend on the androgen/androgen receptor pathway. Therefore, androgen deprivation therapy (ADT) has become the primary treatment option for prostate cancer. Patients with metastatic prostate cancer who receive (ADT) have shown increased quality of life. However, survival benefit with ADT is reduced dramatically in castration-resistant prostate cancer (CRPC). Androgen receptor (AR) continues to be functional in CRPC through various mechanisms. It is …