Medical Specialties Commons^™

Achieving Value In Spine Surgery: 10 Major Cost Contributors., Lucas R. Philipp, Adam Leibold, Aria Mahtabfar, Thiago Montenegro, Glenn Gonzalez, James Harrop

Department of Neurosurgery Faculty Papers

STUDY DESIGN: Narrative Review.

OBJECTIVES: The increasing cost of healthcare overall and for spine surgery, coupled with the growing burden of spine-related disease and rising demand have necessitated a shift in practice standards with a new emphasis on value-based care. Despite multiple attempts to reconcile the discrepancy between national recommendations for appropriate use and the patterns of use employed in clinical practice, resources continue to be overused-often in the absence of any demonstrable clinical benefit. The following discussion illustrates 10 areas for further research and quality improvement.

METHODS: We present a narrative review of the literature regarding 10 features in …

Bundled Payment Models In Spine Surgery., Kevin Hines, Nikolaos Mouchtouris, Charles Getz, Glenn Gonzalez, Thiago Montenegro, Adam Leibold, James Harrop

Department of Neurosurgery Faculty Papers

STUDY DESIGN: The following is a narrative discussion of bundled payments in spine surgery.

OBJECTIVE: The cost of healthcare in the United States has continued to increase. To lower the cost of healthcare, reimbursement models are being investigated as potential cost saving interventions by driving incentives and quality improvement in fields such a spine surgery.

METHODS: Narrative overview of literature pertaining to bundled payments in spine surgery synthesizing findings from computerized databases and authoritative texts.

RESULTS: Spine surgery is challenging to define payment modes because of high cost variability and surgical decision-making nuances. While implementing bundled care payments in spine …

A Diverse Nation Calls For A Diverse Healthcare Force., Autumn L Saizan, Annyella Douglas, Nada Elbuluk, Susan Taylor

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

The Use Of Actigraphy And Its Impact On Perceived Sleep Quality And Activity Levels In Individuals With Traumatic Brain Injury In An Inpatient Rehabilitation Setting., Lina Shkokani, Amanda Reyes, Bachar Hazim, Jason Kisser, Philip T. Roskos

Conference Presentation Abstracts

No abstract provided.

The Last Frontier For Global Non-Communicable Disease Action: The Emergency Department—A Cross-Sectional Study From East Africa, Christine Ngaruiya, Mbatha Wambua, Thomas Kedera Mutua, Daniel Owambo, Morgan Muchemi, Kipkoech Rop, Kaitlin R. Maciejewski, Rebecca Leff, Mugane Mutua, Benjamin Wachira

Emergency Medicine, East Africa

Introduction: Deaths due to non-communicable diseases (NCDs) have surpassed those due to communicable diseases globally and are projected to do so in Africa by 2030. Despite demonstrated effectiveness in high-income country (HIC) settings, the ED is a primary source of NCD care that has been under-prioritized in Africa. In this study, we assess the burden of leading NCDs and NCD risk factors in Kenyan Casualty Department patients to inform interventions targeting patients with NCDs in emergency care settings.

Materials and methods: Using the WHO STEPwise approach to surveillance (STEPS) tool and the Personal Health Questionnaire (PHQ-9), we conducted a …

Comorbidities And Complications In Adults With Pyruvate Kinase Deficiency., Audra N. Boscoe, Yan Yan, Elizabeth Hedgeman, Eduard J. Van Beers, Hanny Al-Samkari, Wilma Barcellini, Stefan W. Eber, Bertil Glader, Hassan M. Yaish, Satheesh Chonat, Mukta Sharma, Kevin H M Kuo, Ellis J. Neufeld, Heng Wang, Madeleine Verhovsek, Sujit Sheth, Rachael F. Grace

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: Pyruvate kinase (PK) deficiency is caused by PKLR gene mutations, leading to defective red blood cell glycolysis and hemolytic anemia. Rates of comorbidities and complications by transfusion history and relative to the general population remain poorly quantified.

METHODS: Data for patients aged ≥ 18 years with two confirmed PKLR mutations were obtained from the PK deficiency Natural History Study (NCT02053480). Frequencies of select conditions were compared with an age- and sex-matched cohort from a general insured US population without PK deficiency.

RESULTS: Compared with the matched population (n = 1220), patients with PK deficiency (n = 122) had significantly …

Meal-Induced Symptoms In Children With Dyspepsia-Relationships To Sex And The Presence Of Gastroparesis, Liz Febo-Rodriguez, Bruno P Chumpitazi, Salma Musaad, Andrew C Sher, Robert J Shulman

Children’s Nutrition Research Center Staff Publications

Objectives: To test the hypothesis that in children with dyspepsia, prospective symptom severity following ingestion of a meal would correlate with percent gastric retention, and those ultimately diagnosed with gastroparesis would report worse symptoms.

Study design: Prospective, single-center study with 104 children with dyspepsia completing a prospective dyspepsia symptom questionnaire before and after eating a standardized Tougas meal during gastric emptying scintigraphy. Main outcomes included correlation between gastric retention and symptoms and comparison of symptom severity between those with and without gastroparesis.

Results: Fifty-two children (50%) had gastroparesis (gastroparesis: 12.5 ± 2.9 years, 65% female; nongastroparesis: 13.0 ± 2.9 years, …

Research Participation Of Minor Adolescents In Foster Care, Jenny Francis, Jane Andresen, Heidi Kloster, Jill Mcleigh, Alexis Guzman, Susan Rosenthal

Health Status, Outcomes, and Literacy and Healthcare Utilization

In this study we evaluated published studies about foster care to: (1) determine the types of data used; (2) describe the degree to which a sexual/reproductive health topic was addressed; and (3) describe the consent process.

For questions about this study or others, please email [email protected]

childrens.com/fostercare

Nhanes Iii Mortality Follow Up: Social Determinants Creating Disparity Within The Health Outcomes Of Persons With Diabetes, Claire B. Adams

University Honors Theses

Given the recent research into the social determinants affecting health outcomes, the goal of this thesis is to examine whether a non-urban setting, among other social determinants of health, increases the risk of mortality among the United States diabetic population. We examined the relationship of urban and non-urban diabetes rates among those aged 40-74 years using a national sample of diabetic and nondiabetic Americans. The data was pulled from the Third National Health and Nutrition Examination Survey (NHANES III) which was conducted from 1988 to 1994. After excluding pregnant women, those who did not complete a fasting AM glucose, and …

Association Of Race With Lung Cancer Risk Among Adults Undergoing Lung Cancer Screening., Christine S Shusted, Nathaniel R Evans, Hee-Soon Juon, Gregory C Kane, Julie A Barta

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

No abstract provided.

Serotonergic Therapy In Epilepsy, Frank Gilliam, Hrvoje Hećimović, Matthew S. Gentry

School of Medicine Publications

Purpose of review

The serotonergic system is implicated in multiple aspects of epilepsy, including seizure susceptibility, sudden unexpected death in epilepsy (SUDEP), and comorbid depression. Despite the complexity of serotonin’s effects on various neuronal networks, ongoing research provides considerable insight into the role of serotonin in human epilepsy. This review explores the potential roles of serotonergic therapies to improve clinical outcomes in epilepsy.

Recent findings

In recent decades research has markedly increased our knowledge of the diverse effects of serotonin on brain function. Animal models of epilepsy have identified the influence of serotonin on seizure threshold in specific brain regions, …

Demand Satisfied By Modern Contraceptive Among Married Women Of Reproductive Age In Kenya, Peter Gichangi, Michael Waithaka, Mary Thiongo, Alfred Agwanda, Scott Radloff, Amy Tsui, Linea Zimmerman, Marleen Temmerman

Obstetrics and Gynaecology, East Africa

Background: Demand for family planning met/satisfied with modern contraceptive methods (mDFPS) has been proposed to track progress in Family Planning (FP) programs for Sustainable Development Goals. This study measured mDFPS among married women of reproductive age (MWRA) in Kenya to identify which groups were not being reached by FP programs.

Materials and methods: Performance, Monitoring and Accountability 2020 (PMA2020) survey data from 2014–2018 was used. PMA2020 surveys are cross-sectional including women 15–49 years. PMA2020 used a 2-stage cluster design with urban/rural regions as strata with random selection of households. Univariate and multivariate analysis was done using stata V15.

Results: Of …

Cerebral Perfusion Using The Resistive Index On Doppler Ultrasound In Extremely Premature Newborns With Ventriculomegaly, Rawad Obeid, Marni Jacobs, Taeun Chang, An N. Massaro, Dorothy Bulas, Anna Penn

Conference Presentation Abstracts

Background: In extremely premature newborns, the effect of ventriculomegaly, as seen on cranial ultrasound (CUS), on cerebral perfusion is not well studied. The resistive index (RI) (Figure-1) is a marker of change of the flow velocity on Doppler ultrasound that could be used to understand this effect.

Objective: To identify the following: 1- The normal RI values in premature infants without intraventricular hemorrhage (IVH), 2- The relation between the RI in the major intracerebral arteries and the ventricular size on CUS using the fronto-temporal horn ratio (FTHR) in newborns with and without IVH, and 3-The association with white matter injury …

Evali During The Covid-19 Pandemic: A Needle In The Ground Glass, Derek J. Fikse Do, Matthew Nimmo Do, Alexandra Amaducci Do, Kenneth D. Katz Md

Department of Emergency Medicine

No abstract provided.

Escape This Emergency Room: Simulation Education During A Pandemic, Michael C. Nguyen Md, Nicole Elliott Do, Julie A. Fritzges Do, Louis Morolla Do, Steven A Johnson Md

Department of Emergency Medicine

No abstract provided.

Interventions To Reduce Emergency Department Demand During A Pandemic, Cynthia Wang Bs, Bryan G. Kane Md, Jason L. Forgeon Md, Justin Giordano Do, Armando Orta Md, Richard S. Mackenzie Md

Department of Emergency Medicine

No abstract provided.

Level I Nodal Positivity As A Factor For Involvement Of The Submandibular Gland In Oral Cavity Carcinoma: A Case Series Report, Hamdan Ahmed Pasha, Rahim Dhanani, Shayan Khalid, Kulsoom Ghias, Mumtaz Jamshed Khan

Section of Otolaryngology, Head & Neck Surgery

Introduction: The routine practice of neck dissection in the surgical management of oral carcinoma has evolved into a more functionally conservative approach. Over time, the rationale for removal of the submandibular gland has been questioned. Routine extirpation of the submandibular gland can aggravate the xerostomia experienced by many patients, significantly affecting their quality of life.
Objective: The objective of the present study was to determine the incidence of submandibular gland metastases in oral cavity carcinoma and to identify possible factors that may affect their involvement.
Methods: A total of 149 cases of oral carcinoma presenting at a private tertiary care …

Intimate Partner Violence Is A Barrier To Antiretroviral Therapy Adherence Among Hiv - Positive Women: Evidence From Government Facilities In Kenya, Bornice C. Biomndo, Alexander Bergmann, Nils Lahmann, Lukoye Atwoli

Internal Medicine, East Africa

Introduction: Intimate Partner Violence (IPV) is linked to low engagement with HIV management services and adverse clinical outcomes, including poor ART adherence. In sub-Saharan Africa, studies on pregnant/postpartum women and transactional sex workers have produced divergent evidence regarding IPV’s association with poor ART adherence. We investigate this association among a broad group of women.

Methods: We sampled 408 HIV-positive women receiving free ART from different types of HIV clinics at government health facilities, assessing for IPV exposure by a current partner, ART adherence rate, and other factors that affect ART adherence (e.g. education, disclosure). ART adherence rates were measured using …

Targeting Resistance To Radiation-Immunotherapy In Cold Hnsccs By Modulating The Treg-Dendritic Cell Axis., Michael W. Knitz, Thomas E. Bickett, Laurel B. Darragh, Ayman J. Oweida, Shilpa Bhatia, Benjamin Van Court, Shiv Bhuvane, Miles Piper, Jacob Gadwa, Adam C. Mueller, Diemmy Nguyen, Varuna Nangia, Douglas G. Osborne, Xiyuan Bai, Sarah E. Ferrara, Mary-Keara Boss, Andrew Goodspeed, Matthew A. Burchill, Beth A. Jirón Tamburini, Edward D. Chan, Curtis R. Pickering, Eric T. Clambey, Sana D. Karam

Department of Radiation Oncology Faculty Papers

BACKGROUND: Numerous trials combining radiation therapy (RT) and immunotherapy in head and neck squamous cell carcinoma (HNSCC) are failing. Using preclinical immune cold models of HNSCC resistant to RT-immune checkpoint inhibitors, we investigate therapeutic approaches of overcoming such resistance by examining the differential microenvironmental response to RT.

METHODS: We subjected two HPV-negative orthotopic mouse models of HNSCC to combination RT, regulatory T cells (Treg) depletion, and/or CD137 agonism. Tumor growth was measured and intratumorous and lymph node immune populations were compared among treatment groups. Human gene sets, genetically engineered mouse models DEREG and BATF3-/-, flow and time-of-flight cytometry, RNA-Seq, …

Gastric Volvulus In Adults In A Tertiary Care Hospital Karachi, Pakistan: A Case Series, Om Parkash, Roger Christopher Gill, Iman Qaiser, Muhammad Sharoz Rabbani, Tabish Chawla, Hasnain Zafar

Section of Gastroenterology

Gastric volvulus is a rare surgical emergency which is rare in children and occasionally presents in adults. It results due to pathological malrotation of the stomach along its longitudinal or short axis. The condition, if not treated promptly, can result in increased morbidity and carries a high risk of death. Very few cases have been reported in literature regards this important clinical condition. Early decompression and repair of anatomical defects are the corner stone of its management. There is a dire need to develop guidelines and algorithms for management and treatment of this rare condition to improve patient outcome, prevent …

Mechanical Support Of Superior Cavopulmonary (Glenn) Physiology To Heart Transplantation, Edo K S Bedzra, Aliessa P. Barnes, Brian Birnbaum, James D. St. Louis

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Quality Outcomes For Pediatric Colorectal Surgery Treated During Short-Term International Medical Service Trips At A Dedicated Site In Honduras., Wilfried Krois, Rebecca M. Rentea, Pastora X. Hernandez, Juan Craniotis-Rios, Richard J. Wood, Marc A. Levitt, Carlos A. Reck-Burneo

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Short-term international medical service trips (MSTs) provide specialized care in resource-constrained countries. There are limited data on immediate and long-term reported outcomes following specialty MST. We hypothesized that dedicated collaborative MST team and host institution produce outcomes and results comparable to those of high-income settings. Our primary aim was to analyze the long-term surgical and functional outcomes of our specialty-specific MSTs following five years of annual MST in Honduras.

METHODS: We performed a single-institution retrospective analysis of 56 children who underwent colorectal and pelvic reconstructive operations between 2014 and 2018. Demographics, diagnosis, comorbidities, type of repair, long-term complications, and …

Assessment Of Nutritional Status In Children With Kidney Diseases-Clinical Practice Recommendations From The Pediatric Renal Nutrition Taskforce., Christina L. Nelms, Vanessa Shaw, Larry A. Greenbaum, Caroline Anderson, An Desloovere, Dieter Haffner, Michiel J S Oosterveld, Fabio Paglialonga, Nonnie Polderman, Leila Qizalbash, Lesley Rees, José Renken-Terhaerdt, Jetta Tuokkola, Johan Vande Walle, Rukshana Shroff, Bradley A. Warady

Manuscripts, Articles, Book Chapters and Other Papers

In children with kidney diseases, an assessment of the child's growth and nutritional status is important to guide the dietary prescription. No single metric can comprehensively describe the nutrition status; therefore, a series of indices and tools are required for evaluation. The Pediatric Renal Nutrition Taskforce (PRNT) is an international team of pediatric renal dietitians and pediatric nephrologists who develop clinical practice recommendations (CPRs) for the nutritional management of children with kidney diseases. Herein, we present CPRs for nutritional assessment, including measurement of anthropometric and biochemical parameters and evaluation of dietary intake. The statements have been graded using the American …

The Impact Of 2020 And The Future Of Cardiology Training: How Do We Innovate?, Prasanti Alekhya Kotta, Brittany Corso, Yevgeniy Brailovsky, Estefania Oliveros

Division of Cardiology Faculty Papers

No abstract provided.

Preparticipation Evaluation Of The Special Olympics Athlete, Mary M. Stephens, Md, Mph

Department of Family & Community Medicine Presentations and Grand Rounds

Objectives

• By the end of this module the student will be able to describe the components of a pre-participation sports evaluation.
• By the end of this module the student will be able to articulate an assessment for atlantoaxial instability.
• By the end of this module the student will be able to apply the learned knowledge from the module to a case study.
• By the end of this module the student will be able to recommend appropriate anticipatory guidance to the athlete.

Distraction Osteogenesis With Temporal Bone Remodeling For Unicoronal Craniosynostosis, Phuong D Nguyen, Ahmed Belal, George N Washington, Matthew R Greives, David I Sandberg, Stephen A Fletcher, Manish N Shah

Faculty, Staff and Student Publications

Unicoronal craniosynostosis correction with fronto-orbital advancement and cranial vault remodeling has traditionally been the gold standard. Distraction osteogenesis has the advantage of increased size of movement without constriction of the scalp and decreased morbidity. Although fronto-orbital advancement and cranial vault remodeling are usually performed at 6 months of age or later, distraction osteogenesis is performed at a younger age, between 3 and 6 months, to take advantage of the infant bony physiology. Herein, the authors demonstrate a case of distraction osteogenesis for unicoronal craniosynostosis in a 3-month-old female with significant improvement of her orbital, nasal, and frontal symmetry.

The video …

Discovery And Fine-Mapping Of Height Loci Via High-Density Imputation Of Gwass In Individuals Of African Ancestry, Mariaelisa Graff, Anne E Justice, Kristin L Young, Eirini Marouli, Xinruo Zhang, Rebecca S Fine, Elise Lim, Victoria Buchanan, Kristin Rand, Mary F Feitosa, Mary K Wojczynski, Lisa R Yanek, Yaming Shao, Rebecca Rohde, Adebowale A Adeyemo, Melinda C Aldrich, Matthew A Allison, Christine B Ambrosone, Stefan Ambs, Christopher Amos, Donna K Arnett, Larry Atwood, Elisa V Bandera, Traci Bartz, Diane M Becker, Sonja I Berndt, Leslie Bernstein, Lawrence F Bielak, William J Blot, Erwin P Bottinger, Donald W Bowden, Jonathan P Bradfield, Jennifer A Brody, Ulrich Broeckel, Gregory Burke, Brian E Cade, Qiuyin Cai, Neil Caporaso, Chris Carlson, John Carpten, Graham Casey, Stephen J Chanock, Guanjie Chen, Minhui Chen, Yii-Der I Chen, Wei-Min Chen, Alessandra Chesi, Charleston W K Chiang, Lisa Chu, Gerry A Coetzee, David V Conti, Richard S Cooper, Mary Cushman, Ellen Demerath, Sandra L Deming, Latchezar Dimitrov, Jingzhong Ding, W Ryan Diver, Qing Duan, Michele K Evans, Adeyinka G Falusi, Jessica D Faul, Myriam Fornage, Caroline Fox, Barry I Freedman, Melissa Garcia, Elizabeth M Gillanders, Phyllis Goodman, Omri Gottesman, Struan F A Grant, Xiuqing Guo, Hakon Hakonarson, Talin Haritunians, Tamara B Harris, Curtis C Harris, Brian E Henderson, Anselm Hennis, Dena G Hernandez, Joel N Hirschhorn, Lorna Haughton Mcneill, Timothy D Howard, Barbara Howard, Ann W Hsing, Yu-Han H Hsu, Jennifer J Hu, Chad D Huff, Dezheng Huo, Sue A Ingles, Marguerite R Irvin, Esther M John, Karen C Johnson, Joanne M Jordan, Edmond K Kabagambe, Sun J Kang, Sharon L Kardia, Brendan J Keating, Rick A Kittles, Eric A Klein, Suzanne Kolb, Laurence N Kolonel, Charles Kooperberg, Lewis Kuller, Abdullah Kutlar, Leslie Lange, Carl D Langefeld, Loic Le Marchand, Hampton Leonard, Guillaume Lettre, Albert M Levin, Yun Li, Jin Li, Yongmei Liu, Youfang Liu, Simin Liu, Kurt Lohman, Vaneet Lotay, Yingchang Lu, William Maixner, Joann E Manson, Barbara Mcknight, Yan Meng, Keri L Monda, Kris Monroe, Jason H Moore, Thomas H Mosley, Poorva Mudgal, Adam B Murphy, Rajiv Nadukuru, Mike A Nalls, Katherine L Nathanson, Uma Nayak, Amidou N'Diaye, Barbara Nemesure, Christine Neslund-Dudas, Marian L Neuhouser, Sarah Nyante, Heather Ochs-Balcom, Temidayo O Ogundiran, Adesola Ogunniyi, Oladosu Ojengbede, Hayrettin Okut, Olufunmilayo I Olopade, Andrew Olshan, Badri Padhukasahasram, Julie Palmer, Cameron D Palmer, Nicholette D Palmer, George Papanicolaou, Sanjay R Patel, Curtis A Pettaway, Patricia A Peyser, Michael F Press, D C Rao, Laura J Rasmussen-Torvik, Susan Redline, Alex P Reiner, Suhn K Rhie, Jorge L Rodriguez-Gil, Charles N Rotimi, Jerome I Rotter, Edward A Ruiz-Narvaez, Benjamin A Rybicki, Babatunde Salako, Michele M Sale, Maureen Sanderson, Eric Schadt, Pamela J Schreiner, Claudia Schurmann, Ann G Schwartz, Daniel A Shriner, Lisa B Signorello, Andrew B Singleton, David S Siscovick, Jennifer A Smith, Shad Smith, Elizabeth Speliotes, Margaret Spitz, Janet L Stanford, Victoria L Stevens, Alex Stram, Sara S Strom, Lara Sucheston, Yan V Sun, Salman M Tajuddin, Herman Taylor, Kira Taylor, Bamidele O Tayo, Michael J Thun, Margaret A Tucker, Dhananjay Vaidya, David J Van Den Berg, Sailaja Vedantam, Mara Vitolins, Zhaoming Wang, Erin B Ware, Sylvia Wassertheil-Smoller, David R Weir, John K Wiencke, Scott M Williams, L Keoki Williams, James G Wilson, John S Witte, Margaret Wrensch, Xifeng Wu, Jie Yao, Neil Zakai, Krista Zanetti, Babette S Zemel, Wei Zhao, Jing Hua Zhao, Wei Zheng, Degui Zhi, Jie Zhou, Xiaofeng Zhu, Regina G Ziegler, Joe Zmuda, Alan B Zonderman, Bruce M Psaty, Ingrid B Borecki, L Adrienne Cupples, Ching-Ti Liu, Christopher A Haiman, Ruth Loos, Maggie C Y Ng, Kari E North

Faculty, Staff and Student Publications

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two …

Efficacy, Pharmacokinetics, And Safety Over 48 Weeks With Ibalizumab-Based Therapy In Treatment-Experienced Adults Infected With Hiv-1: A Phase 2a Study, Joseph C Gathe, Robin L Hardwicke, Fernando Garcia, Steven Weinheimer, Stanley T Lewis, Robert Brandon Cash

Faculty, Staff and Student Publications

Ibalizumab, a humanized monoclonal antibody targeting CD4, blocks HIV-1 entry into cells and is the first Food and Drug Adminstration-approved long-acting agent for HIV-1 treatment. In this phase 2a study, 82 HIV-infected adults failing antiretroviral therapy were assigned an individually optimized background regimen (OBR) and randomized 1:1:1 to arm A (15 mg/kg ibalizumab q2wk), arm B (10 mg/kg weekly for 9 weeks, then q2wk), or placebo. Subjects with an inadequate response at week 16 were permitted to cross over to a new OBR plus 15 mg/kg ibalizumab q2wk. At week 16, viral load (VL) reduction was significantly greater than placebo …

Hypoxia-Inducible Factor–1Α–Dependent Induction Of Mir122 Enhances Hepatic Ischemia Tolerance, Cynthia Ju, Meng Wang, Eunyoung Tak, Boyun Kim, Christoph Emontzpohl, Yang Yang, Xiaoyi Yuan, Huban Kutay, Yafen Liang, David R Hall, Wasim A Dar, J Steve Bynon, Peter Carmeliet, Kalpana Ghoshal, Holger K Eltzschig

Faculty, Staff and Student Publications

Hepatic ischemia and reperfusion (IR) injury contributes to the morbidity and mortality associated with liver transplantation. microRNAs (miRNAs) constitute a family of noncoding RNAs that regulate gene expression at the posttranslational level through the repression of specific target genes. Here, we hypothesized that miRNAs could be targeted to enhance hepatic ischemia tolerance. A miRNA screen in a murine model of hepatic IR injury pointed us toward the liver-specific miRNA miR122. Subsequent studies in mice with hepatocyte-specific deletion of miR122 (miR122loxP/loxP Alb-Cre+ mice) during hepatic ischemia and reperfusion revealed exacerbated liver injury. Transcriptional studies implicated hypoxia-inducible factor-1α (HIF1α) in the induction …

Hypoxia-Inducible Factor-Dependent Induction Of Myeloid-Derived Netrin-1 Attenuates Natural Killer Cell Infiltration During Endotoxin-Induced Lung Injury, Nathaniel K Berg, Jiwen Li, Boyun Kim, Tingting Mills, Guangsheng Pei, Zhongming Zhao, Xiangyun Li, Xu Zhang, Wei Ruan, Holger K Eltzschig, Xiaoyi Yuan

Faculty, Staff and Student Publications

Sepsis and sepsis-associated lung inflammation significantly contribute to the morbidity and mortality of critical illness. Here, we examined the hypothesis that neuronal guidance proteins could orchestrate inflammatory events during endotoxin-induced lung injury. Through a targeted array, we identified netrin-1 as the top upregulated neuronal guidance protein in macrophages treated with lipopolysaccharide (LPS). Furthermore, we found that netrin-1 is highly enriched in infiltrating myeloid cells, particularly in macrophages during LPS-induced lung injury. Transcriptional studies implicate hypoxia-inducible factor HIF-1α in the transcriptional induction of netrin-1 during LPS treatment. Subsequently, the deletion of netrin-1 in the myeloid compartment (Ntn1