Medical Specialties Commons^™

Risk Factors And Prognostic Significance Of Anemia In Children With Hiv Infection On Antiretroviral Therapy, Joseph Lubega, Amanda Grimes, Gladstone Airewele, Shaun Bulsara, Taylor Olmsted Kim, Heather Haq, Erin Peckham-Gregory, Sebastian R Wanless, Peter Elyanu, Philippa Musoke, Mwita Lumumba, Adeodata Kekitiinwa, Mogomotsi Matshaba, Jenny Despotovic, Michael Scheurer

Faculty, Staff and Students Publications

OBJECTIVES: To establish the incidence, risk factors and prognostic effect of anemia in children living with HIV (CLWH).

DESIGN: Retrospective nested case-control study of patients 0-18 years in five centers in sub-Saharan Africa, 2004-2014.

METHODS: Incident cases of anemia were identified from electronic records and matched with CLWH without anemia. We calculated the incidence density of anemia and used conditional logistic regression to evaluate its association with risk factors, stratified by severity and type of anemia. We used a Cox proportional hazards model to evaluate the impact of anemia on survival.

RESULTS: Two thousand, one hundred and thirty-seven children were …

Foxi3 Haploinsufficiency Contributes To Low T-Cell Receptor Excision Circles And T-Cell Lymphopenia, Rajarshi Ghosh, Marita Bosticardo, Sunita Singh, Morgan Similuk, Ottavia M Delmonte, Francesca Pala, Christine Peng, Colleen Jodarski, Michael D Keller, Ivan K Chinn, Andrew K Groves, Luigi D Notarangelo, Magdalena A Walkiewicz, Javier Chinen, Vanessa Bundy

Faculty, Staff and Students Publications

BACKGROUND: Newborn screening can identify neonatal T-cell lymphopenia through detection of a low number of copies of T-cell receptor excision circles in dried blood spots collected at birth. After a positive screening result, further diagnostic testing is required to determine whether the subject has severe combined immunodeficiency or other causes of T-cell lymphopenia. Even after thorough evaluation, approximately 15% of children with a positive result of newborn screening for T-cell receptor excision circles remain genetically undiagnosed. Identifying the underlying genetic etiology is necessary to guide subsequent clinical management and family planning.

OBJECTIVE: We sought to elucidate the genetic basis of …

A Phase I/Ii Trial Of Nivolumab Plus Ipilimumab In Children And Young Adults With Relapsed/Refractory Solid Tumors: A Children's Oncology Group Study Advl1412, Kara L Davis, Elizabeth Fox, Emasenyie Isikwei, Joel M Reid, Xiaowei Liu, Charles G Minard, Stephan Voss, Stacey L Berg, Brenda J Weigel, Crystal L Mackall

Faculty, Staff and Students Publications

PURPOSE: In many cancers, nivolumab in combination with ipilimumab improves response rates compared with either agent alone, but the combination has not been evaluated in childhood cancer. We conducted a phase I/II trial of nivolumab plus ipilimumab in children and young adults with recurrent/refractory solid tumors.

PATIENTS AND METHODS: ADVL1412, Part C assessed safety of nivolumab plus ipilimumab at two dose levels (DL): DL1 1 mg/kg of each drug and DL2 3 mg/kg nivolumab plus 1 mg/kg ipilimumab. Part D evaluated response at the recommended phase II dose (RP2D) in Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma. Part E tested DL3 (1 …

Comparative Effectiveness Of Surveillance Colonoscopy Intervals On Colorectal Cancer Outcomes In A National Cohort Of Patients With Inflammatory Bowel Disease, Hyun-Seok Kim, Ruben Hernaez, Shubhada Sansgiry, Akbar K Waljee, Frank I Scott, James D Lewis, Hashem B El-Serag, Jason K Hou

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Surveillance colonoscopy is recommended to reduce colorectal cancer (CRC)-related morbidity and mortality in patients with inflammatory bowel disease (IBD). The comparative effectiveness of varying colonoscopy intervals on CRC outcomes among patients with IBD is unknown.

METHODS: We performed a retrospective cohort study of patients with confirmed CRC within a cohort of 77,824 patients with IBD during 2000 to 2015 in the National Veterans Health Administration. We examined the association between colonoscopy surveillance intervals on CRC stage, treatment, or all-cause and cancer-specific mortality. The interval of colonoscopy prior to CRC diagnosis was categorized as those performed within <1 >year, …

Lack Of Consensus Among Healthcare Professionals At A Large Academic Medical Center On The Use Of Exome Sequencing For Prenatal Diagnosis, Kylie Johnson, Hadi Erfani, Mohamad Ali Maktabi, Ignatia Van Den Veyver, Salma Nassef

Center for Medical Ethics and Health Policy Staff Publications

Prenatal exome sequencing (ES) is increasingly used for prenatal diagnosis because emerging data indicate it has incremental diagnostic benefit in pregnancies with fetal anomalies without identified genetic abnormalities by karyotyping and chromosomal microarray analysis. The aim of this study was to evaluate the medical community's attitude toward the clinical utility and use of exome sequencing for prenatal diagnosis and to address differences in attitudes and responses by type of practitioner, level of training, and years passed since last full-time training. We analyzed the answers of 109 trainees and professionals in the fields of genetic counseling, laboratory science, and medicine to …

Cic Missense Variants Contribute To Susceptibility For Spina Bifida, Xiao Han, Xuanye Cao, Vanessa Aguiar-Pulido, Wei Yang, Menuka Karki, Paula Andrea Pimienta Ramirez, Robert M Cabrera, Ying Linda Lin, Bogdan J Wlodarczyk, Gary M Shaw, M Elizabeth Ross, Cuilian Zhang, Richard H Finnell, Yunping Lei

Faculty, Staff and Students Publications

Neural tube defects (NTDs) are congenital malformations resulting from abnormal embryonic development of the brain, spine, or spinal column. The genetic etiology of human NTDs remains poorly understood despite intensive investigation. CIC, homolog of the Capicua transcription repressor, has been reported to interact with ataxin-1 (ATXN1) and participate in the pathogenesis of spinocerebellar ataxia type 1. Our previous study demonstrated that CIC loss of function (LoF) variants contributed to the cerebral folate deficiency syndrome by downregulating folate receptor 1 (FOLR1) expression. Given the importance of folate transport in neural tube formation, we hypothesized that CIC variants could contribute to increased …

Implementation Of Systematic Safety Checklists In A Neurocritical Care Unit: A Quality Improvement Study, César E Escamilla-Ocañas, Gabriel Torrealba-Acosta, Pitchaiah Mandava, Muhammad Suhaib Qasim, Bárbara Gutiérrez-Flores, Eric Bershad, Mohammad Hirzallah, Chethan P Venkatasubba Rao, Rahul Damani

Faculty, Staff and Students Publications

Background and objectives: Structured and systematised checklists have been shown to prevent complications and improve patient care. We evaluated the implementation of systematic safety checklists in our neurocritical care unit (NCCU) and assessed its effect on patient outcomes.

Design/methods: This quality improvement project followed a Plan-Do-Study-Act (PDSA) methodology. A checklist for medication reconciliation, thromboembolic prophylaxis, glycaemic control, daily spontaneous awakening, breathing trial, diet, catheter/lines duration monitoring and antibiotics de-escalation was implemented during daily patient rounds. Main outcomes included the rate of new infections, mortality and NCCU-length of stay (LOS). Intervened patients were compared with historical controls after propensity score and …

Incidence Of An Insulin-Requiring Hyperglycemic Syndrome In Sars-Cov-2-Infected Young Individuals: Is It Type 1 Diabetes?, Massimo Pietropaolo, Peter Hotez, Nick Giannoukakis

Center for Medical Ethics and Health Policy Staff Publications

Pancreatic ACE2 receptor expression, together with increased prevalence of insulin-requiring hyperglycemia in patients with coronavirus disease 2019 (COVID-19), suggested that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pancreatic infection might trigger a β-cell-selective inflammation precipitating autoimmune type 1 diabetes (T1D). We examined T1D incidence in patients with COVID-19 inside a large, global population using a "big data" approach. The incidence in 0-30-year-old patients with confirmed COVID-19 over an ∼15-month period from the beginning of the COVID-19 pandemic was compared with an age-matched population without COVID-19 inside the TriNetX COVID-19 Research Network (>80 million deidentified patient electronic medical records globally). …

Proteasome Inhibitors Silence Oncogenes In Multiple Myeloma Through Localized Histone Deacetylase 3 (Hdac3) Stabilization And Chromatin Condensation, Laure Maneix, Polina Iakova, Shannon E Moree, Joanne I Hsu, Ragini M Mistry, Fabio Stossi, Premal Lulla, Zheng Sun, Ergun Sahin, Sarvari V Yellapragada, André Catic

Faculty, Staff and Students Publications

Proteasome inhibitors have become the standard of care for multiple myeloma (MM). Blocking protein degradation particularly perturbs the homeostasis of short-lived polypeptides such as transcription factors and epigenetic regulators. To determine how proteasome inhibitors directly impact gene regulation, we performed an integrative genomics study in MM cells. We discovered that proteasome inhibitors reduce the turnover of DNA-associated proteins and repress genes necessary for proliferation through epigenetic silencing. Specifically, proteasome inhibition results in the localized accumulation of histone deacetylase 3 (HDAC3) at defined genomic sites, which reduces H3K27 acetylation and increases chromatin condensation. The loss of active chromatin at super-enhancers critical …

Long-Term Relugolix Combination Therapy For Symptomatic Uterine Leiomyomas, Ayman Al-Hendy, Andrea S Lukes, Alfred N Poindexter, Roberta Venturella, Claudio Villarroel, Laura Mckain, Yulan Li, Rachel B Wagman, Elizabeth A Stewart

Faculty, Staff and Students Publications

OBJECTIVE: In the LIBERTY 1 and LIBERTY 2 placebo-controlled trials, once-daily relugolix combination therapy reduced menstrual blood loss volume and pain in women with heavy menstrual bleeding associated with uterine leiomyomas and was well tolerated, with preservation of bone mineral density (BMD) through 24 weeks. Here we report the long-term efficacy and safety of relugolix combination therapy treatment for up to 52 weeks.

METHODS: Women with uterine leiomyoma-associated heavy menstrual bleeding who completed any treatment arm in either the LIBERTY 1 or LIBERTY 2 trial were eligible to enroll in a 28-week long-term extension study. All participants received once-daily relugolix …

Outcomes Of Audio-Instructed And Video-Instructed Dispatcher-Assisted Cardiopulmonary Resuscitation: A Systematic Review And Meta-Analysis, Karol Bielski, Bernd W Böttiger, Michal Pruc, Aleksandra Gasecka, Mariusz Sieminski, Milosz J Jaguszewski, Jacek Smereka, Natasza Gilis-Malinowska, Frank W Peacock, Lukasz Szarpak

Faculty, Staff and Students Publications

BACKGROUND: The present meta-analysis of clinical and simulation trials aimed to compare video-instructed dispatcher-assisted bystander cardiopulmonary resuscitation (V-DACPR) with conventional audio-instructed dispatcher-assisted bystander cardiopulmonary resuscitation (C-DACPR).

METHODS: We searched PubMed, Embase, Web of Science, Cochrane Collaboration databases and Scopus from inception until June 10, 2021. The primary outcomes were the prehospital return of spontaneous circulation (ROSC), survival to hospital discharge, and survival to hospital discharge with a good neurological outcome for clinical trials, and chest compression quality for simulation trials. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) indicated the pooled effect. The analyses were performed …

Human Loss-Of-Function Variants In The Serotonin 2c Receptor Associated With Obesity And Maladaptive Behavior, Yang He, Bas Brouwers, Hesong Liu, Hailan Liu, Katherine Lawler, Edson Mendes De Oliveira, Dong-Kee Lee, Yongjie Yang, Aaron R Cox, Julia M Keogh, Elana Henning, Rebecca Bounds, Aliki Perdikari, Vikram Ayinampudi, Chunmei Wang, Meng Yu, Longlong Tu, Nan Zhang, Na Yin, Junying Han, Nikolas A Scarcelli, Zili Yan, Kristine M Conde, Camille Potts, Jonathan C Bean, Mengjie Wang, Sean M Hartig, Lan Liao, Jianming Xu, Inês Barroso, Jacek Mokrosinski, Yong Xu, I Sadaf Farooqi

Children’s Nutrition Research Center Staff Publications

Serotonin reuptake inhibitors and receptor agonists are used to treat obesity, anxiety and depression. Here we studied the role of the serotonin 2C receptor (5-HT2CR) in weight regulation and behavior. Using exome sequencing of 2,548 people with severe obesity and 1,117 control individuals without obesity, we identified 13 rare variants in the gene encoding 5-HT2CR (HTR2C) in 19 unrelated people (3 males and 16 females). Eleven variants caused a loss of function in HEK293 cells. All people who carried variants had hyperphagia and some degree of maladaptive behavior. Knock-in male mice harboring a human loss-of-function HTR2C variant developed …

Standards For Evaluating Neonatal Growth Outcomes Using Individualized Pathological Growth Potential Realization Indices, Russell L Deter, Wesley Lee, Roberto Romero

Faculty, Staff and Students Publications

OBJECTIVE: Provide standards for detecting neonatal growth abnormalities with the average pathological Growth Potential Realization Index (av. pGPRI).

METHODS: Individualized Growth Assessment (IGA) evaluations of 117 neonates with normal growth outcomes were carried out using measurements of WT, HC, AC, ThC and CHL. Growth Potential Realization Index (GPRI) values for each parameter were calculated from predicted and actual birth measurements, the former obtained using Rossavik size models derived from the second-trimester growth potential estimates. Subtraction of either the upper and lower boundaries of GPRI reference ranges from these GPRI measurements gave + pGPRI and - pGPRI measurements. GPRI's within their …

Baseline Microperimetry And Oct In The Rush2a Study: Structure-Function Association And Correlation With Disease Severity, Eleonora M Lad, Jacque L Duncan, Wendi Liang, Maureen G Maguire, Allison R Ayala, Isabelle Audo, David G Birch, Joseph Carroll, Janet K Cheetham, Todd A Durham, Abigail T Fahim, Jessica Loo, Zengtian Deng, Dibyendu Mukherjee, Elise Heon, Robert B Hufnagel, Bin Guan, Alessandro Iannaccone, Glenn J Jaffe, Christine N Kay, Michel Michaelides, Mark E Pennesi, Ajoy Vincent, Christina Y Weng, Sina Farsiu

Faculty, Staff and Students Publications

PURPOSE: To investigate baseline mesopic microperimetry (MP) and spectral domain optical coherence tomography (OCT) in the Rate of Progression in USH2A-related Retinal Degeneration (RUSH2A) study.

DESIGN: Natural history study METHODS: Setting: 16 clinical sites in Europe and North AmericaStudy Population: Participants with Usher syndrome type 2 (USH2) (N = 80) or autosomal recessive nonsyndromic RP (ARRP) (N = 47) associated with biallelic disease-causing sequence variants in USH2AObservation Procedures: General linear models were used to assess characteristics including disease duration, MP mean sensitivity and OCT intact ellipsoid zone (EZ) area. The associations between mean sensitivity and EZ area with other measures, …

Impact Of Diabetes Status And Related Factors On Covid-19-Associated Hospitalization: A Nationwide Retrospective Cohort Study Of 116,370 Adults With Sars-Cov-2 Infection., Erin M. Tallon, Osagie Ebekozien, Janine Sanchez, Vincent S. Staggs, Diana Ferro, Ryan Mcdonough, Carla Demeterco-Berggren, Sarit Polsky, Patricia Gomez, Neha Patel, Priya Prahalad, Ori Odugbesan, Priyanka Mathias, Joyce M. Lee, Chelsey Smith, Chi-Ren Shyu, Mark A. Clements

Manuscripts, Articles, Book Chapters and Other Papers

Aims: We examined diabetes status (no diabetes; type 1 diabetes [T1D]; type 2 diabetes [T2D]) and other demographic and clinical factors as correlates of coronavirus disease 2019 (COVID-19)-related hospitalization. Further, we evaluated predictors of COVID-19-related hospitalization in T1D and T2D.

Methods: We analyzed electronic health record data from the de-identified COVID-19 database (December 2019 through mid-September 2020; 87 US health systems). Logistic mixed models were used to examine predictors of hospitalization at index encounters associated with confirmed SARS-CoV-2 infection.

Results: In 116,370 adults ( >=18 years old) with COVID-19 (93,098 no diabetes; 802 T1D; 22,470 T2D), factors that independently increased …

Avpcancerfree: Impact Of A Digital Behavior Change Intervention On Parental Hpv Vaccine –Related Perceptions And Behaviors, Ross Shegog, Lara S Savas, C Mary Healy, Erica L Frost, Sharon P Coan, Efrat K Gabay, Sharice M Preston, Stanley W Spinner, Mathew Wilbur, Elisabeth Becker, Travis Teague, Sally W Vernon

Faculty, Staff and Student Publications

Parent hesitancy contributes to reduced HPV vaccination rates. The HPVcancerfree app (HPVCF) was designed to assist parents in making evidence-based decisions regarding HPV vaccination. This study examined if parents of vaccine-eligible youth (11-12 yrs.) who use HPVCF in addition to usual care demonstrate significantly more positive intentions and attitudes toward HPV vaccination and greater HPV vaccination rates compared to those not using HPVCF. Clinics (n = 51) within a large urban pediatric network were randomly assigned to treatment (HPVCF + usual care) or comparison (usual care only) conditions in a RCT conducted between September 2017 and February 2019. Parents completed …

An Ai-Driven Clinical Care Pathway To Reduce 30-Day Readmission For Chronic Obstructive Pulmonary Disease (Copd) Patients, Lin Wang, Guihua Li, Chika F Ezeana, Richard Ogunti, Mamta Puppala, Tiancheng He, Xiaohui Yu, Solomon S Y Wong, Zheng Yin, Aaron W Roberts, Aryan Nezamabadi, Pingyi Xu, Adaani Frost, Robert E Jackson, Stephen T C Wong

Faculty, Staff and Student Publications

Healthcare regulatory agencies have mandated a reduction in 30-day hospital readmission rates and have targeted COPD as a major contributor to 30-day readmissions. We aimed to develop and validate a simple tool deploying an artificial neural network (ANN) for early identification of COPD patients with high readmission risk. Using COPD patient data from eight hospitals within a large urban hospital system, four variables were identified, weighted and validated. These included the number of in-patient admissions in the previous 6 months, the number of medications administered on the first day, insurance status, and the Rothman Index on hospital day one. An …

Hippo-Yap Signaling Maintains Sinoatrial Node Homeostasis, Mingjie Zheng, Rich G Li, Jia Song, Xiaolei Zhao, Li Tang, Shannon Erhardt, Wen Chen, Bao H Nguyen, Xiao Li, Min Li, Jianxin Wang, Sylvia M Evans, Vincent M Christoffels, Na Li, Jun Wang

Faculty, Staff and Student Publications

BACKGROUND: The sinoatrial node (SAN) functions as the pacemaker of the heart, initiating rhythmic heartbeats. Despite its importance, the SAN is one of the most poorly understood cardiac entities because of its small size and complex composition and function. The Hippo signaling pathway is a molecular signaling pathway fundamental to heart development and regeneration. Although abnormalities of the Hippo pathway are associated with cardiac arrhythmias in human patients, the role of this pathway in the SAN is unknown.

METHODS: We investigated key regulators of the Hippo pathway in SAN pacemaker cells by conditionally inactivating the Hippo signaling kinases

RESULTS: We …

Digital Biomarkers Of Gait And Balance In Diabetic Foot, Measurable By Wearable Inertial Measurement Units: A Mini Review, Gu Eon Kang, Angeloh Stout, Ke'vaughn Waldon, Seungmin Kang, Amanda L Killeen, Peter A Crisologo, Michael Siah, Daniel Jupiter, Bijan Najafi, Ashkan Vaziri, Lawrence A Lavery

Center on Aging Staff Publications

People with diabetic foot frequently exhibit gait and balance dysfunction. Recent advances in wearable inertial measurement units (IMUs) enable to assess some of the gait and balance dysfunction associated with diabetic foot (i.e., digital biomarkers of gait and balance). However, there is no review to inform digital biomarkers of gait and balance dysfunction related to diabetic foot, measurable by wearable IMUs (e.g., what gait and balance parameters can wearable IMUs collect? Are the measurements repeatable?). Accordingly, we conducted a web-based, mini review using PubMed. Our search was limited to human subjects and English-written papers published in peer-reviewed journals. We identified …

The Fate Of Early Perichondrial Cells In Developing Bones, Yuki Matsushita, Angel Ka Yan Chu, Chiaki Tsutsumi-Arai, Shion Orikasa, Mizuki Nagata, Sunny Y Wong, Joshua D Welch, Wanida Ono, Noriaki Ono

Faculty, Staff and Student Publications

In endochondral bone development, bone-forming osteoblasts and bone marrow stromal cells have dual origins in the fetal cartilage and its surrounding perichondrium. However, how early perichondrial cells distinctively contribute to developing bones remain unidentified. Here we show using in vivo cell-lineage analyses that Dlx5+ fetal perichondrial cells marked by Dlx5-creER do not generate cartilage but sustainably contribute to cortical bone and marrow stromal compartments in a manner complementary to fetal chondrocyte derivatives under the regulation of Hedgehog signaling. Postnatally, Dlx5+ fetal perichondrial cell derivatives preferentially populate the diaphyseal marrow stroma with a dormant adipocyte-biased state and are refractory to parathyroid …

Inactivation Of Lats1/2 Drives Luminal-Basal Plasticity To Initiate Basal-Like Mammary Carcinomas, Joseph G Kern, Andrew M Tilston-Lunel, Anthony Federico, Boting Ning, Amy Mueller, Grace B Peppler, Eleni Stampouloglou, Nan Cheng, Randy L Johnson, Marc E Lenburg, Jennifer E Beane, Stefano Monti, Xaralabos Varelas

Faculty, Staff and Student Publications

Basal-like breast cancers, an aggressive breast cancer subtype that has poor treatment options, are thought to arise from luminal mammary epithelial cells that undergo basal plasticity through poorly understood mechanisms. Using genetic mouse models and ex vivo primary organoid cultures, we show that conditional co-deletion of the LATS1 and LATS2 kinases, key effectors of Hippo pathway signaling, in mature mammary luminal epithelial cells promotes the development of Krt14 and Sox9-expressing basal-like carcinomas that metastasize over time. Genetic co-deletion experiments revealed that phenotypes resulting from the loss of LATS1/2 activity are dependent on the transcriptional regulators YAP/TAZ. Gene expression analyses of …

Metabolic Targeting Of Nrf2 Potentiates The Efficacy Of The Trap1 Inhibitor G-Tpp Through Reduction Of Ros Detoxification In Colorectal Cancer, Hong-Yuan Tsai, Mary P Bronner, Jordon K March, John F Valentine, Noah F Shroyer, Lisa A Lai, Teresa A Brentnall, Sheng Pan, Ru Chen

Faculty, Staff and Students Publications

Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial homolog of HSP90 chaperones. It plays an important role in protection against oxidative stress and apoptosis by regulating reactive oxidative species (ROS). To further elucidate the mechanistic role of TRAP1 in regulating tumor cell survival, we used gamitrinib-triphenylphosphonium (G-TPP) to inhibit TRAP1 signaling pathways in colon cancer. Inhibition of TRAP1 by G-TPP disrupted redox homeostasis and induced cell death. However, colon cancers show a wide range of responses to G-TPP treatment through the induction of variable ER stress responses and ROS accumulation. Interestingly, a strong inverse correlation was observed between …

Glial Interference: Impact Of Type I Interferon In Neurodegenerative Diseases, Ethan Roy, Wei Cao

Faculty, Staff and Student Publications

No abstract provided.

Using Genomic Variation To Distinguish Ovarian High-Grade Serous Carcinoma From Benign Fallopian Tubes, Jesus Gonzalez-Bosquet, Nicholas D Cardillo, Henry D Reyes, Brian J Smith, Kimberly K Leslie, David P Bender, Michael J Goodheart, Eric J Devor

Department of Obstetrics and Gynecology Faculty Papers

The preoperative diagnosis of pelvic masses has been elusive to date. Methods for characterization such as CA-125 have had limited specificity. We hypothesize that genomic variation can be used to create prediction models which accurately distinguish high grade serous ovarian cancer (HGSC) from benign tissue.

Methods: In this retrospective, pilot study, we extracted DNA and RNA from HGSC specimens and from benign fallopian tubes. Then, we performed whole exome sequencing and RNA sequencing, and identified single nucleotide variants (SNV), copy number variants (CNV) and structural variants (SV). We used these variants to create prediction models to distinguish cancer from benign …

Clinical And Molecular Insights Into Gastrointestinal Dysfunction In Myotonic Dystrophy Types 1 & 2, Janel A M Peterson, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic dystrophy (DM) is a highly variable, multisystemic disorder that clinically affects one in 8000 individuals. While research has predominantly focused on the symptoms and pathological mechanisms affecting striated muscle and brain, DM patient surveys have identified a high prevalence for gastrointestinal (GI) symptoms amongst affected individuals. Clinical studies have identified chronic and progressive dysfunction of the esophagus, stomach, liver and gallbladder, small and large intestine, and rectum and anal sphincters. Despite the high incidence of GI dysmotility in DM, little is known regarding the pathological mechanisms leading to GI dysfunction. In this review, we summarize results from clinical and …

Interventions For Preventing And Ameliorating Cognitive Deficits In Adults Treated With Cranial Irradiation, Matthew A Kirkman, Julia Day, Karin Gehring, Karolis Zienius, David Grosshans, Martin Taphoorn, Jing Li, Paul D Brown

Faculty, Staff and Student Publications

BACKGROUND: Cognitive deficits are common in people who have received cranial irradiation and have a serious impact on daily functioning and quality of life. The benefit of pharmacological and non-pharmacological treatment of cognitive deficits in this population is unclear. This is an updated version of the original Cochrane Review published in Issue 12, 2014.

OBJECTIVES: To assess the effectiveness of interventions for preventing or ameliorating cognitive deficits in adults treated with cranial irradiation.

SEARCH METHODS: For this review update we searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE via Ovid, Embase via Ovid, and PsycInfo via Ovid to 12 …

Variation In Human Water Turnover Associated With Environmental And Lifestyle Factors, Yosuke Yamada, Xueying Zhang, Mary E T Henderson, Hiroyuki Sagayama, Herman Pontzer, Daiki Watanabe, Tsukasa Yoshida, Misaka Kimura, Philip N Ainslie, Lene F Andersen, Liam J Anderson, Lenore Arab, Issad Baddou, Kweku Bedu-Addo, Ellen E Blaak, Stephane Blanc, Alberto G Bonomi, Carlijn V C Bouten, Pascal Bovet, Maciej S Buchowski, Nancy F Butte, Stefan G Camps, Graeme L Close, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Lara R Dugas, Simon Eaton, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Annelies H Goris, Michael Gurven, Lewis G Halsey, Catherine Hambly, Asmaa El Hamdouchi, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Kitty P Kempen, William E Kraus, Wantanee Kriengsinyos, Robert F Kushner, Estelle V Lambert, William R Leonard, Nader Lessan, Corby K Martin, Anine C Medin, Erwin P Meijer, James C Morehen, James P Morton, Marian L Neuhouser, Theresa A Nicklas, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Roberto A Rabinovich, Susan B Racette, David A Raichlen, Eric Ravussin, Leanne M Redman, John J Reilly, Rebecca M Reynolds, Susan B Roberts, Albertine J Schuit, Luis B Sardinha, Analiza M Silva, Anders M Sjödin, Eric Stice, Samuel S Urlacher, Giulio Valenti, Ludo M Van Etten, Edgar A Van Mil, Jonathan C K Wells, George Wilson, Brian M Wood, Jack A Yanovski, Alexia J Murphy-Alford, Cornelia U Loechl, Amy H Luke, Jennifer Rood, Klaas R Westerterp, William W Wong, Motohiko Miyachi, Dale A Schoeller, John R Speakman

Children’s Nutrition Research Center Staff Publications

Water is essential for survival, but one in three individuals worldwide (2.2 billion people) lack access to safe drinking water. Water intake requirements largely reflect water turnover (WT), the water used by the body each day. We investigated the determinants of human WT in 5,604 people from the ages of 8 days to 96 years from 26 countries using isotope tracking (2H) methods. Age, body size, and composition were significantly associated with WT as were physical activity, athletic status, pregnancy, socioeconomic status, and environmental characteristics (latitude, altitude, air temperature, and humidity). People in countries with low human development index (HDI) …

Non-Invasive Tear Break-Up Detection With The Kowa Dr-1Α And Its Relationship To Dry Eye Clinical Severity, Stephen Pflugfelder, Lauren Nakhleh, Yasushi Kikukawa, Shin Tanaka, Takuya Kosugi

Faculty, Staff and Students Publications

The purpose of this study is to compare visual versus software detection of non-invasive tear break-up with the KOWA DR-1α tear interferometer and investigate the relationship between non-invasive tear break-up time (NIBUT) and dry eye clinical severity. Tear interferometry with the KOWA DR-1α, together with a standardized comprehensive ocular surface/tear evaluation, was performed on 348 consecutive eyes. Investigator visually detected or software detected non-invasive tear break-up and NIBUT were measured and compared on a subset of these examinations. The relationship between software-detected NIBUT and categorical dry eye severity based on irritation symptoms and corneal and conjunctival dye staining scores was …

The Innate Immune System In Cardiovascular Diseases And Its Role In Doxorubicin-Induced Cardiotoxicity, Anchit Bhagat, Pradeep Shrestha, Eugenie S Kleinerman

Faculty, Staff and Student Publications

Innate immune cells are the early responders to infection and tissue damage. They play a critical role in the initiation and resolution of inflammation in response to insult as well as tissue repair. Following ischemic or non-ischemic cardiac injury, a strong inflammatory response plays a critical role in the removal of cell debris and tissue remodeling. However, persistent inflammation could be detrimental to the heart. Studies suggest that cardiac inflammation and tissue repair needs to be tightly regulated such that the timely resolution of the inflammation may prevent adverse cardiac damage. This involves the recognition of damage; activation and release …

Genomic Profiling For Clinical Decision Making In Myeloid Neoplasms And Acute Leukemia, Eric J Duncavage, Adam Bagg, Robert P Hasserjian, Courtney D Dinardo, Lucy A Godley, Ilaria Iacobucci, Siddhartha Jaiswal, Luca Malcovati, Alessandro M Vannucchi, Keyur P Patel, Daniel A Arber, Maria E Arcila, Rafael Bejar, Nancy Berliner, Michael J Borowitz, Susan Branford, Anna L Brown, Catherine A Cargo, Hartmut Döhner, Brunangelo Falini, Guillermo Garcia-Manero, Torsten Haferlach, Eva Hellström-Lindberg, Annette S Kim, Jeffery M Klco, Rami Komrokji, Mignon Lee-Cheun Loh, Sanam Loghavi, Charles G Mullighan, Seishi Ogawa, Attilio Orazi, Elli Papaemmanuil, Andreas Reiter, David M Ross, Michael Savona, Akiko Shimamura, Radek C Skoda, Francesc Solé, Richard M Stone, Ayalew Tefferi, Matthew J Walter, David Wu, Benjamin L Ebert, Mario Cazzola

Faculty, Staff and Student Publications

Myeloid neoplasms and acute leukemias derive from the clonal expansion of hematopoietic cells driven by somatic gene mutations. Although assessment of morphology plays a crucial role in the diagnostic evaluation of patients with these malignancies, genomic characterization has become increasingly important for accurate diagnosis, risk assessment, and therapeutic decision making. Conventional cytogenetics, a comprehensive and unbiased method for assessing chromosomal abnormalities, has been the mainstay of genomic testing over the past several decades and remains relevant today. However, more recent advances in sequencing technology have increased our ability to detect somatic mutations through the use of targeted gene panels, whole-exome …