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Nicholas A Smith, Paul C Baresel, Conner L Jackson, Sidney Ogolla, Eunice N Toko, Sara Heit, Erwan Piriou, Odada P Sumba, Jaap M Middeldorp, Kathryn L Colborn, Rosemary Rochford
Background: The EBV viral glycoprotein gp350 has been proposed as a candidate antigen for an EBV vaccine. However, the proposed formulations of these vaccines have not taken into account the presence of two unique EBV strains (EBV-1 and EBV-2) present in areas of high incidence of the EBV associated cancer, Burkitt's lymphoma. Methods: In this study, we analyze the kinetics of EBV-1 and EBV-2 infection in an asymptomatic infant cohort from Kisumu, Kenya. We also analyzed the kinetics of the antibody response against five EBV antigens, gp350 (IgG and IgA), VCA (IgG), EBNA-1 (IgG), EAd (IgG), and Zta (IgG)...
October 12, 2018: Journal of Infectious Diseases
Hui Lv, Lei Ye, Qian Liu, Song-Guo Li, Tao Li, Na-Li Huang, Yi Gao, Li-Bin Fan, Wei-Dong Du
PURPOSE: Epstein-Barr virus (EBV) is a ubiquitous human gamma herpes virus that infects human epithelial cells and B lymphocytes. EXPERIMENTAL DESIGN: A simple antigen-probed biochip, which was modified with S-S-PEG-COOH and was used as a label-free high-throughput screening method for a combined detection of EBV capsid antigen IgM antibody, capsid antigen IgG antibody and nuclear antigen IgG antibody. RESULTS: This protein biochip had similar feasibility, sensitivity and specificity in comparison with Liaison CLIA...
October 11, 2018: Proteomics. Clinical Applications
Zeyang Wang, Zhi Lv, Hanxi Ding, Qian Xu, Liping Sun, Jingjing Jing, Yuan Yuan
The study aimed to investigate the role of serum EBV-VCA IgG in assessing gastric cancer (GC) risk and prognosis. A total of 1790 Northern Chinese participants with pathologically confirmed disease underwent EBV-VCA IgG serologic testing using enzyme-linked immunosorbent assay (ELISA), including 821 controls, 410 atrophic gastritis (AG) patients, and 559 GC patients. We found that positive EBV-VCA IgG was significantly associated with GC and its precursor, conferring a 1.55- and 1.36-fold increased risk of GC and AG, respectively (P = 0...
October 10, 2018: Cancer Medicine
Arthur L Caplan, Brendan Parent, Jeffrey Kahn, Wendy Dean, Laura L Kimberly, W P Andrew Lee, Eduardo D Rodriguez
BACKGROUND: Despite early skepticism, the field of vascularized composite allotransplantation (VCA) has demonstrated feasibility. The ethics of VCA have moved past doubts about the morality of attempting such transplant to how to conduct them ethically. METHODS: Leaders of each program performing and/or evaluating VCA in the United States were invited to participate in a working group to assess the state and future of VCA ethics and policy. Four meetings were held over the course of 1 year to describe key challenges and potential solutions...
October 8, 2018: Transplantation
Andrew J Lindford, Heikki Mäkisalo, Hannu Jalanko, Jouni Lauronen, Veli-Jukka Anttila, Susanna Juteau, Antti-Jussi Ämmälä, Anna Eskola, Samuli Saarni, Helena Isoniemi, Antti Mäkitie, Patrik Lassus
AIM: We herein describe the establishment of the Helsinki Vascularized Composite Allotransplantation (VCA) program and its execution in the first two face transplant cases. METHODS & PATIENTS: The Helsinki VCA program initially required the fulfillment of legal, hospital, financial, and ethical requirements. Thereafter, the assembling of a multidisciplinary team commenced. A team of Plastic, maxillofacial and ENT surgeons comprise the facial VCA team. The protocol involves collaboration with the Solid Organ Transplant (SOT) team, transplant immunology, immunosuppression, microbiology, psychiatric evaluation, well-defined VCA indications and informed consent...
September 22, 2018: Journal of Plastic, Reconstructive & Aesthetic Surgery: JPRAS
Shaun D Mendenhall, Michael T Ginnetti, Justin D Sawyer, Steven J Verhulst, Bradford L West, L Scott Levin, Michael W Neumeister
Background: Vascularized composite allotransplantation (VCA) is an emerging and growing field. Little is known about the prevalence and distribution of the adult potential donor population in the United States now that it falls under the oversight of the United Network for Organ Sharing (UNOS). Methods: We assessed the UNOS database from 2008 to 2015 to estimate the prevalence and distribution of adult potential vascularized composite allograft donors. Donor inclusion and exclusion criteria were developed in a way to minimize risk to recipients and were applied to the dataset...
June 2018: Plastic and Reconstructive Surgery. Global Open
Jessica B Chang, William J Rifkin, Marc A Soares, April Duckworth, Nakul Rao, Yee Cheng Low, Jonathan P Massie, Piul S Rabbani, Pierre B Saadeh, Daniel J Ceradini
Background: Widespread application of vascularized composite allotransplantation (VCA) is currently limited by the required lifelong systemic immunosuppression and its associated morbidity and mortality. This study evaluated the efficacy of ex vivo (after procurement but before transplantation) engineering of allografts using small interfering RNA to knockdown major histocompatibility complex I (MHC-I) and prolong rejection-free survival. Methods: Endothelial cells (ECs) were transfected with small interfering RNA targeted against MHC-I (siMHC-I) for all in vitro experiments...
June 2018: Plastic and Reconstructive Surgery. Global Open
Min Ji Sohn, Jin Min Cho, Jin Soo Moon, Jae Sung Ko, Hye Ran Yang
Primary Epstein-Barr virus (EBV) infection is common in childhood, and dual positivity of serum EBV IgM and cytomegalovirus (CMV) IgM antibodies occur in some cases. This study aimed to evaluate the cause of EBV and CMV IgM dual positivity to determine whether it represents a false-positive finding or a true coinfection.A total of 494 children diagnosed with primary EBV infection, manifesting as infectious mononucleosis, were recruited. The diagnosis was based on positive EBV viral capsid antigen (VCA) IgM antibodies, and serum CMV IgM antibodies and liver enzymes were also evaluated in 149 subjects...
September 2018: Medicine (Baltimore)
Jennifer L Wainright, Christopher L Wholley, John Rosendale, Wida S Cherikh, Darren Di Battista, David K Klassen
BACKGROUND: Vascularized composite allograft (VCA) transplants include diverse organ types and are made possible primarily by deceased donors. METHODS: We used Organ Procurement and Transplantation Network (OPTN) data to characterize VCA deceased donors (n=66 of 70) in the United States 1998-2017 and compare their characteristics with those of kidney donors in 2017. RESULTS: Through December 31, 2017, 20 transplant programs performed 72 deceased donor VCA transplants, with organs donated by 70 donors, including 30 upper limb (17 unilateral and 13 bilateral) and 11 face donors...
September 17, 2018: Transplantation
Hui-Yun Cheng, Sheri K L Tay, Chih-Jen Wen, Chih-Fan Lin, Aline Yen-Ling Wang, Ling-Yi Shih, Shiao-Chin Liu, Eiji Kobayashi, Cheng-Hung Lin, Fu-Chan Wei
BACKGROUND: Tipping the balance toward regulatory T cells (Tregs) through adoptive cell therapy has shown promise to induce transplantation tolerance. Although such strategy has been explored in many mice organ transplantation studies, less knowledge was available in rat systems. Furthermore, the behaviors of the transferred cells have not been well studied in real-time fashion. METHODS: Tregs from naïve LEW rats were purified in two steps with the autoMACS system...
2018: PloS One
Hamidreza Yazdi, Ara Nazarian, Jim S Wu, Arash Amiri, Poopak Hafezi, Margaret Babikian, Amin Mohamadi, Reza Pakdaman, Mohammad Ghorbanhoseini
Background: The valgus cut angle (VCA) of the distal femur in Total Knee Arthroplasty (TKA) is measured preoperatively on three-joint alignment radiographs. The anatomical axis of the femur can be described as the anatomical axis of the full length of the femur or as the anatomical axis of the distal half of the femur, which may result in different angles in some cases. During TKA, the anatomical axis of the femur is determined by intramedullary femoral guides, which may follow the distal half or near full anatomical axis, based on the length of the femoral guide...
July 2018: Archives of Bone and Joint Surgery
Sofia Espinoza-Sanchez, Lauren Ann Metskas, Steven Z Chou, Elizabeth Rhoades, Thomas D Pollard
We used fluorescence spectroscopy and EM to determine how binding of ATP, nucleation-promoting factors, actin monomers, and actin filaments changes the conformation of Arp2/3 complex during the process that nucleates an actin filament branch. We mutated subunits of Schizosaccharomyces pombe Arp2/3 complex for labeling with fluorescent dyes at either the C termini of Arp2 and Arp3 or ArpC1 and ArpC3. We measured Förster resonance energy transfer (FRET) efficiency (ETeff ) between the dyes in the presence of the various ligands...
September 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
Sue V McDiarmid
PURPOSE OF REVIEW: This review will focus on the lessons learned over several decades of solid organ transplantation in children, and their relevance to the emerging field of pediatric VCA. Particular attention will be focused on the risk-benefit ratio of immunosuppression as it applies to children receiving a life-enhancing transplant as compared with a life-saving transplant. Potential indications for pediatric VCA will be considered. RECENT FINDINGS: The report in 2015 of the first child to receive a VCA, bilateral upper extremity grafts from a nonrelated deceased donor, is a seminal event...
October 2018: Current Opinion in Organ Transplantation
Thomas H Tung, Susan E Mackinnon
PURPOSE OF REVIEW: The current review will discuss the current understanding of nerve regeneration in vascularized composite allotransplantation (VCA). The success of proximal arm and leg transplants has been hampered by the limitations of nerve regrowth across long distances resulting in poor regeneration and functional recovery. Relevant research in stem-cell therapies to overcome these issues will be reviewed. RECENT FINDINGS: The effect of rejection on nerve regeneration in the VCA may be unpredictable and may be quite different for the nerve allograft...
October 2018: Current Opinion in Organ Transplantation
Emmanuel Morelon, Palmina Petruzzo, Jean Kanitakis
PURPOSE OF REVIEW: Vascularized composite allografts (VCA), which restore severely damaged body parts that cannot be repaired with conventional surgical techniques, often undergo acute skin rejection episodes in the early postgraft period. Although the risk of human VCA to be affected by chronic rejection was initially unknown, such cases were recently observed. RECENT FINDINGS: Chronic rejection targets preferentially the skin (dermal sclerosis, adnexal atrophy, necrosis) and vessels (graft vasculopathy) and may cause graft dysfunction, often resulting in ischemic graft loss...
October 2018: Current Opinion in Organ Transplantation
Charles Anton Fries, Carole Yasay Villamaria, Jerry Richard Spencer, Shari Lawson, Lin Wang, Thomas Raj, E George Wolf, Bijaya Kumar Parida, Vijay Saradhi Gorantla, Rory Frederick Rickard, Michael Robert Davis
BACKGROUND:  Ischemia-reperfusion injury (IRI) precipitates acute rejection of vascularized composite allografts (VCA). Hyperbaric preservation of tissues ex vivo, between harvest and revascularization, may reduce IRI and mitigate acute rejection of VCA. METHODS:  A porcine heterotopic musculocutaneous gracilis flap model was used. In phase 1, control autografts ( n  = 5) were infused with University of Wisconsin Solution (UWS) and stored at 4°C for 3 hours...
August 12, 2018: Journal of Reconstructive Microsurgery
Wida S Cherikh, Linda C Cendales, Christopher L Wholley, Jennifer Wainright, Vijay S Gorantla, David K Klassen, Sue McDiarmid, L Scott Levin
On July 3, 2014, the Organ Procurement and Transplantation Network/United Network for Organ Sharing was charged with the oversight of Vascularized Composite Allograft (VCA) procurement and transplantation in the U.S. As of December 31, 2017, 61 VCA programs at 27 centers were approved in the U.S. Fifty candidates have been added to the waiting list at 15 centers. Twenty-eight VCA transplants have been performed at 14 programs (10 upper limb, 10 uterus, 5 craniofacial, 1 scalp, 1 abdominal wall, and 1 penile)...
August 9, 2018: American Journal of Transplantation
Laura C Burlage, Shannon N Tessier, Joanna W Etra, Korkut Uygun, Gerald Brandacher
PURPOSE OF REVIEW: In this review, we discuss novel strategies that allow for extended preservation of vascularized composite allografts and their potential future clinical implications for the field of vascularized composite allotransplantation (VCA). RECENT FINDINGS: The current gold standard in tissue preservation - static cold preservation on ice - is insufficient to preserve VCA grafts for more than a few hours. Advancements in the field of VCA regarding matching and allocation, desensitization, and potential tolerance induction are all within reasonable reach to achieve; these are, however, constrained by limited preservation time of VCA grafts...
October 2018: Current Opinion in Organ Transplantation
Adriano Taddeo, Catherine Tsai, Esther Vögelin, Robert Rieben
PURPOSE OF REVIEW: The long-term adverse effects of immunosuppressive treatment, the high rate of acute rejection and the development of chronic rejection are the main factors preventing a wider clinical application of vascularized composite allotransplantation (VCA). Targeted immunosuppression using innovative drug delivery systems (DDS) may help to overcome these hurdles, increasing therapeutic efficacy while reducing systemic toxicity. This review provides a summary of the recently developed strategies for targeted delivery of immunosuppressive drugs in VCA...
October 2018: Current Opinion in Organ Transplantation
Gianluca Trevisi, Simon B Eickhoff, Fahmida Chowdhury, Ashwani Jha, Roman Rodionov, Mark Nowell, Anna Miserocchi, Andrew W McEvoy, Parashkev Nachev, Beate Diehl
The medial frontal cortex remains functionally ill-understood; this is reflected by the heterogeneity of behavioural outcomes following damage to the region. We aim to use the rich information provided by extraoperative direct electrical cortical stimulation to enhance our understanding of its functional anatomy. Examining a cohort of 38 epilepsy patients undergoing direct electrical cortical stimulation in the context of presurgical evaluation, we reviewed stimulation findings and classified them in a behavioural framework (positive motor, negative motor, somatosensory, speech disturbances, and "other")...
July 6, 2018: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
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