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1. Fam49b dampens TCR signal strength to regulate survival of positively selected thymocytes and peripheral T cells.

Author

Park, Chan-Su, Guan, Jian, Rhee, Peter, Gonzalez, Federico, Lee, Hee-Sung, Park, Ji-Hyun, Coscoy, Laurent, Robey, Ellen, Shastri, Nilabh, and Sadegh-Nasseri, Scheherazade

Subjects
Fam49b, Rac, T cell development, cytoskeleton remodeling, immunology, inflammation, intraepithelial T cells, mouse, negative selection, Animals, Mice, Cell Survival, Mice, Knockout, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocytes, Thymocytes
Abstract

The fate of developing T cells is determined by the strength of T cell receptor (TCR) signal they receive in the thymus. This process is finely regulated through the tuning of positive and negative regulators in thymocytes. The Family with sequence similarity 49 member B (Fam49b) protein is a newly discovered negative regulator of TCR signaling that has been shown to suppress Rac-1 activity in vitro in cultured T cell lines. However, the contribution of Fam49b to the thymic development of T cells is unknown. To investigate this important issue, we generated a novel mouse line deficient in Fam49b (Fam49b-KO). We observed that Fam49b-KO double positive (DP) thymocytes underwent excessive negative selection, whereas the positive selection stage was unaffected. Fam49b deficiency impaired the survival of single positive thymocytes and peripheral T cells. This altered development process resulted in significant reductions in CD4 and CD8 single-positive thymocytes as well as peripheral T cells. Interestingly, a large proportion of the TCRγδ+ and CD8αα+TCRαβ+ gut intraepithelial T lymphocytes were absent in Fam49b-KO mice. Our results demonstrate that Fam49b dampens thymocytes TCR signaling in order to escape negative selection during development, uncovering the function of Fam49b as a critical regulator of the selection process to ensure normal thymocyte development and peripheral T cells survival.

Published
2024

3. Contributors

Author

Abelson, Jennifer, primary, Aboutanos, Michel B., additional, Abraham, Peter J., additional, Abualruz, Abdul Rahman, additional, Agarwal, Suresh, additional, Agrawal, Devendra K., additional, Alverdy, John C., additional, Aly, Ahmed, additional, Amato, Stas, additional, Anstadt, Michael J., additional, Asensio, Juan A., additional, Avery, Martin, additional, Bailey, Jeffrey A., additional, Barie, Philip S., additional, Becker, Tyson, additional, Beckerman, Daniel, additional, Bedrick, Edward J., additional, Benson, Jamie, additional, Berne, John D., additional, Berry, Cherisse, additional, Berry, Stepheny, additional, Bhat, Sneha G., additional, Bowie, Jason M., additional, Bowyer, Mark W., additional, Bozeman, Matthew C., additional, Bradley, Matthew, additional, Brakenridge, Scott, additional, Brandes, Steven B., additional, Brenner, Megan, additional, Britt, L.D., additional, Brown, Carlos V., additional, Brown, Ian E., additional, Brown, J. Christian, additional, Brown, Tommy, additional, Buckman, Robert F., additional, Burlew, Clay Cothren, additional, Byers, Patricia M., additional, Caban, Kim M., additional, Cancio, Leopoldo C., additional, Cannon, Jeremy W., additional, Cantlie, Shawn M., additional, Carroll, Eben A., additional, Champion, Howard R., additional, Childs, Ed W., additional, Chiu, William C., additional, Christmas, A. Britton, additional, Cioffi, William G., additional, Cocanour, Christine S., additional, Cohen, Mitchell J., additional, Coimbra, Raul, additional, Cook, Alan, additional, Cornell, David L., additional, Cotton, Bryan A., additional, Couture, Daniel E., additional, Cox, Thomas B., additional, Cristancho, Luis Alfonso Bustamante, additional, Croce, Martin A., additional, Croft, Chasen A., additional, Cubano, Miguel A., additional, Dabestani, Parinaz J., additional, Danton, Gary H., additional, Davis, Christopher S., additional, Davis, Kimberly, additional, de Moya, Marc A., additional, Desai, Urmen, additional, Destiné, Henson, additional, Diebel, Lawrence N., additional, Doucet, Jay J., additional, DuBose, Joseph J., additional, Dubov, Wayne E., additional, Duchesne, Juan C., additional, Durham, Rodney M., additional, Durso, Anthony M., additional, Eastridge, Brian, additional, Efron, David T., additional, Efron, Philip A., additional, Elster, Eric, additional, Esposito, Thomas J., additional, Fakhry, Samir M., additional, Feliciano, David V., additional, Fernandez, Carlos, additional, Fernandez-Moure, Joseph S., additional, Fernández, Luis G., additional, Fiorentino, Michele, additional, Firstenberg, Michael S., additional, Flint, Lewis M., additional, Fredericks, Charles J., additional, Fry, Donald E., additional, Galán, Ricardo, additional, Galante, Joseph M., additional, Galvagno, Samuel M., additional, Garcia, Ana Maria, additional, García, Erwin Rodriguez, additional, García-Núñez, Col Luis Manuel, additional, Gentilello, Larry M., additional, Ghanta, Ravi K., additional, Gigena, Alejandro, additional, Gilani, Ramyar, additional, Glance, Laurent G., additional, Goldman, Matthew, additional, Gonzalez, Ernest A., additional, Gonzalez, Richard P., additional, Grabo, Daniel, additional, Gross, Ronald I., additional, Gummadi, Sriharsha, additional, Guerrero, Whitney M., additional, Gunter, Oliver L., additional, Gurney, Jennifer M., additional, Gutiérrez, Jorge A., additional, Hall, Chad, additional, Hauser, Carl J., additional, Henry, Sharon, additional, Hirshberg, Ashen, additional, Holcomb, John B., additional, Hosmer, David, additional, Hoth, J. Jason, additional, Gomez, Tatiana Hoyos, additional, Hoyt, David B., additional, Humphries, Ashley, additional, Iyengar, Rahul, additional, Jawa, Randeep S., additional, Jessie, Elliot, additional, Johannigman, Jay, additional, Aquino Jose, Victor M., additional, Jurkovich, Gregory J., additional, Kalamchi, Louay, additional, Kapil, Aditi M., additional, Karmy-Jones, Riyad, additional, Kasotakis, George, additional, Kelley, Kathryn C., additional, Keskey, Robert, additional, Kessler, John J., additional, Kim, Dennis Y., additional, Kiraly, Laszlo, additional, Kirton, Orlando C., additional, Kotaru, Tharun R., additional, Kunac, Anastasia, additional, Kwolek, Kinga, additional, Lallemand, Michael S., additional, Ledgerwood, Anna M., additional, Lee, Amanda, additional, Leeper, Christine M., additional, Li, Zhongyu, additional, Libby, Matthew, additional, Lim, Robert B., additional, Liveris, Anna, additional, Livingston, David H., additional, Lobb, Jennifer, additional, Loftus, Tyler J., additional, Lucas, Charles E., additional, Luchette, Fred A., additional, Lundeberg, Megan R., additional, Mackersie, Robert C., additional, Mackey, Kevin E., additional, Magnotti, Louis J., additional, Mah, John W., additional, Maldonado, William Sánchez, additional, Malhotra, Ajai K., additional, Malone, Debra L., additional, Marini, Corrado P., additional, Martin, Matthew J., additional, Marttos, Antonio C., additional, Martyak, Michael T., additional, Mathew, Prakash J., additional, Mattox, Kenneth L., additional, Mayberry, John C., additional, Mazzini, Federico N., additional, McNelis, John, additional, Meallet, Mario A., additional, Meerkov, Meir B.L., additional, Meizoso, Jonathan P., additional, Meredith, J. Wayne, additional, Michetti, Christopher P., additional, Miljkovic, Stephanie S., additional, Miller, Keith R., additional, Miller, Preston R., additional, Minei, Joseph P., additional, Mitchell, Frank L., additional, Moas, Victor M., additional, Mohr, Alicia M., additional, Molnar, Joseph A., additional, Moore, Ernest E., additional, Moore, Frederick A., additional, Moutinho, Manuel, additional, Moysidis, Stavros, additional, Munera, Felipe, additional, Naiditch, Jessica A., additional, Napolitano, Lena M., additional, Narayan, Mayur, additional, Nash, Nicholas A., additional, Nicholson, Kristina J., additional, Nicholson, Susannah, additional, Norwood, Scott H., additional, Nunn, Andrew M., additional, O’Shea, Anne, additional, Osler, Turner M., additional, Pachter, H. Leon, additional, Paladino, Lorenzo, additional, Panthaki, Zubin Jal, additional, Parikh, Manish, additional, Pasquale, Michael D., additional, Patel, Purvi P., additional, Peitzman, Andrew B., additional, Peralta, Ruben, additional, Perez-Alonso, Alejandro J., additional, Pestana, Ivo A., additional, Petrone, Patrizio, additional, Pierre, Edgar J., additional, Pilson, Holly, additional, Polk, Travis, additional, Puyana, Juan Carlos, additional, Quintana, David, additional, Rai, Vikrant, additional, Rajasingh, Charlotte, additional, Ranney, Stephen, additional, Reisbig, Mark D., additional, Reiser, Bibiana Jin, additional, Remick, Kyle N., additional, Rhee, Peter, additional, Rich, Norman M., additional, Richardson, J. David, additional, Richart, Charles M., additional, Rivas, Luis A., additional, Robles, Anamaria J., additional, Rodriguez, Aurelio, additional, Rosengart, Matthew, additional, Rosenthal, Martin D., additional, Rotondo, Michael F., additional, Rowe, Vincent L., additional, Rubano, Jerry A., additional, Rubiano, Andrés M., additional, Ruggero, John M., additional, Rushing, Amy, additional, Salim, Ali, additional, Saillant, Noelle Nugent, additional, Sally, Mitchell B., additional, Salsamendi, Jason, additional, Sanford, Arthur P., additional, Savetamal, Alisa, additional, Scalea, Thomas M., additional, Schecter, William, additional, Schipper, Paul H., additional, Schreiber, Martin A., additional, Schroll, Rebecca W., additional, Schulingkamp, Danielle, additional, Schulman, Carl I., additional, Schulz, John T., additional, Shackelford, Stacy A., additional, Shadis, Ryan, additional, Shapiro, Marc J., additional, Shatz, David V., additional, Shiroff, Adam M., additional, Sicard, Gregorio, additional, Sifri, Ziad C., additional, Sing, Ronald F., additional, Sisley, Amy, additional, Smith, Brian P., additional, Smith, R. Stephen, additional, Singares, Eduardo Smith, additional, Sola, Richard, additional, Spain, David A., additional, Spencer, Audrey L., additional, Stavas, Joseph, additional, Stawicki, Stanislaw P., additional, Stein, Deborah M., additional, Stewart, Nakosi, additional, Stirparo, Joseph J., additional, Strong, Bethany L., additional, Sukumar, Mithran S., additional, Tadlock, Matthew D., additional, Taylor, John R., additional, Thaller, Seth R., additional, Thomas, Bradley W., additional, Thompson, Ashley M., additional, Tieu, Brandon H., additional, Tillou, Areti, additional, Tinkoff, Glen H., additional, Tisherman, Samuel A., additional, Todd, S. Rob, additional, Tominaga, Gail T., additional, Trammell, Amy Phillips, additional, Trunkey, Donald D., additional, Tuggle, David, additional, Upchurch, Gilbert R., additional, Van, Philbert, additional, VanDerHeyden, Nicole, additional, Vanzant, Erin L., additional, Wall, Matthew J., additional, Wenzl, Florian A., additional, Whitlow, Christopher T., additional, Wiegand, Lucas R., additional, Williams, Timothy K., additional, Wilson, Jonathan L., additional, Yeh, D. Dante, additional, Youngblood, Charles F., additional, and Zhang, Wei, additional

Published
2024
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8. Blast Injuries

Author

DuBose, Joe, Plurad, David S., Rhee, Peter M., Degiannis, Elias, editor, Doll, Dietrich, editor, and Velmahos, George C., editor

Published
2023
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10. Management of Minor Traumatic Brain Injury in an ED Observation Unit

Author

Wheatley, Matthew A., Kapil, Shikha, Lewis, Amanda, Walsh O'Sullivan, Jessica, Armentrout, Joshua, Moran, Tim P., Osborne, Anwar, Moore, Brooks L., Morse, Bryan, Rhee, Peter, Ahmad, Faiz, and Atallah, Hany

Subjects
Observation Medicine, Traumatic Brain Injury
Abstract

Introduction: Traumatic intracranial hemorrhages (TIH) have traditionally been managed in the intensive care unit (ICU) setting with neurosurgery consultation and repeat head CT (HCT) for each patient. Recent publications indicate patients with small TIH and normal neurological examinations who are not on anticoagulation do not require ICU-level care, repeat HCT, or neurosurgical consultation. It has been suggested that these patients can be safely discharged home after a short period of observation in emergency department observation units (EDOU) provided their symptoms do not progress. Methods: This study is a retrospective cross-sectional evaluation of an EDOU protocol for minor traumatic brain injury (mTBI). It was conducted at a Level I trauma center. The protocol was developed by emergency medicine, neurosurgery and trauma surgery and modeled after the Brain Injury Guidelines (BIG). All patients were managed by attendings in the ED with discretionary neurosurgery and trauma surgery consultations. Patients were eligible for the mTBI protocol if they met BIG 1 or BIG 2 criteria (no intoxication, no anticoagulation, normal neurological examination, no or non-displaced skull fracture, subdural or intraparenchymal hematoma up to 7 millimeters, trace to localized subarachnoid hemorrhage), and had no other injuries or medical co-morbidities requiring admission. Protocol in the EDOU included routine neurological checks, symptom management, and repeat HCT for progression of symptoms. The EDOU group was compared with historical controls admitted with primary diagnosis of TIH over the 12 months prior to the initiation of the mTBI protocols. Primary outcome was reduction in EDOU length of stay (LOS) as compared to inpatient LOS. Secondary outcomes included rates of neurosurgical consultation, repeat HCT, conversion to inpatient admission, and need for emergent neurosurgical intervention.  Results: There were 169 patients placed on the mTBI protocol between September 1, 2016 and August 31, 2019. The control group consisted of 53 inpatients. Median LOS (interquartile range [IQR]) for EDOU patients was 24.8 (IQR: 18.8 – 29.9) hours compared with a median LOS for the comparison group of 60.2 (IQR: 45.1 – 85.0) hours (P < .001). In the EDOU group 47 (27.8%) patients got a repeat HCT compared with 40 (75.5%) inpatients, and 106 (62.7%) had a neurosurgical consultation compared with 53 (100%) inpatients. Subdural hematoma was the most common type of hemorrhage. It was found in 60 (35.5%) patients, and subarachnoid hemorrhage was found in 56 cases (33.1%). Eleven patients had multicompartment hemorrhage of various classifications. Twelve (7.1%) patients required hospital admission from the EDOU. None of the EDOU patients required emergent neurosurgical intervention.  Conclusion: Patients with minor TIH can be managed in an EDOU using an mTBI protocol and discretionary neurosurgical consults and repeat HCT. This is associated with a significant reduction in length of stay.

Published
2021

11. Primary 3-Month Outcomes of a Double-Blind Randomized Prospective Study (The QUEST Study) Assessing Effectiveness and Safety of Novel High-Frequency Electric Nerve Block System for Treatment of Post-Amputation Pain

Author

Kapural, Leonardo, primary, Melton, Jim, additional, Kim, Billy, additional, Mehta, Priyesh, additional, Sigdel, Abindra, additional, Bautista, Alexander, additional, Petersen, Erika, additional, Slavin, Konstantin, additional, Eidt, John, additional, Wu, Jiang, additional, Elshihabi, Said, additional, Schwalb, Jason, additional, Garrett Jr, H Edward, additional, Veizi, Elias, additional, Barolat, Giancarlo, additional, Rajani, Ravi, additional, Rhee, Peter, additional, Guirguis, Maged, additional, and Mekhail, Nagy, additional

Published
2024
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19. Primary 3-Month Outcomes of a Double-Blind Randomized Prospective Study (The QUEST Study) Assessing Effectiveness and Safety of Novel High-Frequency Electric Nerve Block System for Treatment of Post-Amputation Pain

Author

Kapural,Leonardo, Melton,Jim, Kim,Billy, Mehta,Priyesh, Sigdel,Abindra, Bautista,Alexander, Petersen,Erika, Slavin,Konstantin, Eidt,John, Wu,Jiang, Elshihabi,Said, Schwalb,Jason, Garrett Jr,H Edward, Veizi,Elias, Barolat,Giancarlo, Rajani,Ravi, Rhee,Peter, Guirguis,Maged, Mekhail,Nagy, Kapural,Leonardo, Melton,Jim, Kim,Billy, Mehta,Priyesh, Sigdel,Abindra, Bautista,Alexander, Petersen,Erika, Slavin,Konstantin, Eidt,John, Wu,Jiang, Elshihabi,Said, Schwalb,Jason, Garrett Jr,H Edward, Veizi,Elias, Barolat,Giancarlo, Rajani,Ravi, Rhee,Peter, Guirguis,Maged, and Mekhail,Nagy

Abstract

Leonardo Kapural,1 Jim Melton,2 Billy Kim,3 Priyesh Mehta,4 Abindra Sigdel,5 Alexander Bautista,6 Erika A Petersen,7 Konstantin V Slavin,8,9 John Eidt,10 Jiang Wu,11 Said Elshihabi,12 Jason Matthew Schwalb,13 H Edward Garrett Jr,14 Elias Veizi,15 Giancarlo Barolat,16 Ravi R Rajani,17 Peter C Rhee,18 Maged Guirguis,19 Nagy Mekhail20 1Carolinas Pain Institute and Center for Clinical Research, Winston-Salem, NC, USA; 2Department of Vascular Surgery, Cardiovascular Health Clinic, Oklahoma City, OK, USA; 3Department of Vascular Surgery, The Surgical Clinic, Nashville, TN, USA; 4Department of Pain Medicine, Meta Medical Research Institute, Dayton, OH, USA; 5Department of Surgery, University of Louisville, Louisville, KY, USA; 6Department of Anesthesiology and Perioperative Medicine, University of Louisville, Louisville, KY, USA; 7Department of Neurosurgery, University of Arkansas, Little Rock, AR, USA; 8Department of Neurosurgery, University of Illinois at Chicago, Chicago, IL, USA; 9Department of Neurology, Jesse Brown VA Medical Center, Chicago, IL, USA; 10Department of Vascular Surgery, Baylor Scott and White Heart and Vascular Hospital Dallas, Dallas, TX, USA; 11Department of Anesthesiology & Pain Medicine, University of Washington Medical Center, Seattle, WA, USA; 12Department of Neurosurgery, Legacy Brain & Spine Surgical Center, Atlanta, GA, USA; 13Department of Neurosurgery, Henry Ford Medical Group, Detroit, MI, USA; 14Department of Vascular Surgery, University of Tennessee-Memphis, Memphis, TN, USA; 15Department of Pain Medicine, VA Northeast OH Healthcare System, Cleveland, OH, USA; 16Department of Neurosurgery, Barolat Neuroscience, Presbyterian/St Luke’s Medical Center, Denver, CO, USA; 17Department of Vascular Surgery, Emory University and Grady Memorial Hospital, Atlanta, GA, USA; 18Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA; 19Department of Interventional Pain Management, Ochsner Health System, New Orleans, LA, USA; 20Depar

Published
2024

28. Intravenous Fluids

Author

Rhee, Peter, Evans, Paul M., Salim, Ali, editor, Brown, Carlos, editor, Inaba, Kenji, editor, and Martin, Matthew J., editor

Published
2018
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41. Blast Injuries

Author

DuBose, Joe, Plurad, David S., Rhee, Peter M., Velmahos, George C., editor, Degiannis, Elias, editor, and Doll, Dietrich, editor

Published
2017
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46. Abnormalities of laboratory coagulation tests versus clinically evident coagulopathic bleeding: results from the prehospital resuscitation on helicopters study (PROHS)

Author

Holcomb, John B., Wade, Charles E., Fox, Erin E., Chang, Ronald, Podbielski, Jeanette M., Tomasek, Jeffrey S., del Junco, Deborah J., Swartz, Michael D., DeSantis, Stacia M., Appana, Savitri N., Greene, Thomas J., Yi, Misung, Gonzalez, Michael O., Baraniuk, Sarah, van Belle, Gerald, Leroux, Brian G., Howard, Carrie L., Haymaker, Amanda, Stein, Deborah M., Scalea, Thomas M., Ayd, Benjamin, Das, Pratik, Herrera, Anthony V., Bulger, Eileen M., Robinson, Bryce R.H., Klotz, Patricia, Minhas, Aniqa, Kerby, Jeffrey D., Melton, Sherry M., Williams, Carolyn R., Stephens, Shannon W., Goodman, Michael, Johannigman, Jay A., McMullan, Jason, Branson, Richard D., Gomaa, Dina, Barczak, Christopher, Schreiber, Martin A., Underwood, Samantha J., Watson, Cheri, Zielinski, Martin D., Stubbs, James R., Headlee, Amy, O'Keeffe, Terence, Rhee, Peter, Rokowski, Laurel L., Santoro, John, Jr, Seach, Andrea, Bradford, David, Fealk, Michelle, Latifi, Fortesa, Inaba, Kenji, Kim, Henry, Chudnofsky, Carl, Wong, Monica D., Goodman, Michael D., Appana, Savitri, Johansson, Pär I., Henriksen, Hanne H., Stensballe, Jakob, and Steinmetz, Jacob

Published
2018
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