Cortical reintegration after facial allotransplantation.

Neural plasticity of the brain or its ability to reorganize following injury has likely coincided with the successful clinical correction of severe deformity by facial transplantation since 2005. In this study, we present the cortical reintegration outcomes following syngeneic hemifacial vascularized composite allograft (VCA) in a small animal model. Specifically, changes in the topographic organization and unit response properties of the rodent whisker-barrel somatosensory system were assessed following hemifacial VCA. Clear differences emerged in the barrel-cortex system when comparing naïve and hemiface transplanted animals. Neurons in the somatosensory cortex of transplanted rats had decreased sensitivity albeit increased directional sensitivity compared with naïve rats and evoked responses in transplanted animals were more temporally dispersed. In addition, receptive fields were often topographically mismatched with the indication that the mismatched topography reorganized within adjacent barrel (same row-arc bias following hemifacial transplant). These results suggest subcortical changes in the thalamus and/or brainstem play a role in hemifacial transplantation cortical plasticity and demonstrate the discrete and robust data that can be derived from this clinically relevant small animal VCA model for use in optimizing postsurgical outcomes.NEW & NOTEWORTHY Robust rodent hemifacial transplant model was used to record functional changes in somatosensory cortex after transplantation. Neurons in the somatosensory cortex of face transplant recipients had decreased sensitivity to stimulation of whiskers with increased directional sensitivity vs. naive rats. Transplant recipient cortical unit response was more dispersed in temporary vs. naive rats. Despite histological similarities to naive cortices, transplant recipient cortices had a mix of topographically appropriate and inappropriate whiskered at barrel cortex relationships.

Proton-Functionalized Graphitic Carbon Nitride for Efficient Metal-Free Destruction of Escherichia coli under Low-Power Light Irradiation.

Universal access to clean water has been a global ambition over the years. Photocatalytic water disinfection through advanced oxidation processes has been regarded as one of the promising methods for breaking down microbials. The forefront of this research focuses on the application of metal-free photocatalysts for disinfection to prevent secondary pollution. Graphitic carbon nitride (g-C3 N4 ) has achieved instant attention as a metal-free and visible-light-responsive photocatalyst for various energy and environmental applications. However, the photocatalytic efficiency of g-C3 N4 is still affected by its rapid charge recombination and sluggish electron-transfer kinetics. In this contribution, two-dimensionally protonated g-C3 N4 was employed as metal-free photocatalyst for water treatment and demonstrated 100 % of Escherichia coli within 4 h under irradiation with a 23 W light bulb. The introduction of protonation can modulate the surface charge of g-C3 N4 ; this enhances its conductivity and provides a "highway" for the delocalization of electrons. This work highlights the potential of conjugated polymers in antibacterial application.

Reinventing Yourself Virtually: Fifth Annual Society of Asian Academic Surgeons Virtual Conference.

Virtual forms of communication have been integrated into academic surgery now more than ever. The COVID-19 pandemic accelerated its implementation in an effort to support social-distancing. Academic surgery is now learning valuable lessons from early experiences to optimally integrate this communication mode. The Society of Asian Academic Surgeons convened an expert panel during the society's fifth annual meeting that explores these lessons. Realms of virtual communication including meetings, networking, surgery department administration, social media, application processes, and advice for early or mid-career academic surgeons are explored. Virtual conferences pose a new challenge by removing the in-person component that is evident to be integral to networking, collaboration, and all aspects of academic socialization. Strategies such as creating virtual chat rooms, mentor-mentee virtual introductions, and deliberate interactions can enhance the experience. Virtual administrative meetings require special attention to preparation and strategies to insure engagement. Social media can be a valuable tool to integrate into academic careers but special attention needs to be made to utilize it deliberately and not to shy away from our individuality. The interview process can be enhanced when made virtual to give opportunities to those typically disadvantaged in the usual, in-person process.

Trauma-induced Rejection in Vascularized Composite Allotransplantation.

: Vascularized composite allotransplantation (VCA) is a relatively new field in reconstructive medicine. Likely a result of the unique tissue composition of these allografts-including skin and often a bone marrow component-the immunology and rejection patterns do not always mimic those of the well-studied solid organ transplantations. While the number and type of VCAs performed is rapidly expanding, there is still much to be discovered and understood in the field. With more patients, new findings and patterns emerge and add to our understanding of VCA. Here, we present a case report of an upper extremity transplant recipient with trauma-induced rejection.

Clinical Characteristics of 90 Macrodactyly Cases.

PURPOSE: Macrodactyly is a rare, nonhereditary congenital deformity. Digital enlargement in macrodactyly involves all tissue types and presents alone or as part of a congenital deformity syndromes. Macrodactyly treatment largely depends on surgeons' experience and knowledge. Because there is a paucity of large cohort studies of macrodactyly in the literature, our goal was to retrospectively analyze macrodactyly cases in order to define a better system for diagnosis, classification, and prognosis. METHODS: Medical records of 90 Chinese macrodactyly patients, including demographic characteristics, clinical presentations, anatomical distributions, x-rays, pathological findings, and treatments, were reviewed. Genetic analyses of 12 patients were also reviewed. RESULTS: Disease incidence was similar across sex and geographical regions. Multiple-digit involvement was 2.6 times more frequent than single-digit involvement. The index finger, middle finger, and thumb were most commonly involved. Two digits were affected more often than 3, with the affected digits adjacent in most cases. The affected digit was in the median nerve innervation distribution in 79% of cases and was accompanied by enlargement and fat infiltration of the median nerve. Seven cases had syndactyly. Ten of the 12 cases subjected to PIK3CA mutation analysis were positive. CONCLUSIONS: Macrodactyly represents a heterogeneous group of conditions, without significant sex or geographical predilection, which is usually present at birth. A high PIK3CA mutation-positive rate in affected tissues suggests a similar cellular mechanism for overgrowth in patients with various clinical presentations. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Nitrogen-doped carbon quantum dots-decorated 2D graphitic carbon nitride as a promising photocatalyst for environmental remediation: A study on the importance of hybridization approach.

Growing concerns of water pollution by dye pollutants from the textile industry has led to vast research interest to find green solutions to address this issue. In recent years, heterogeneous photocatalysis has harvested tremendous attention from researchers due to its powerful potential applications in tackling many important energy and environmental challenges at a global level. To fully utilise the broad spectrum of solar energy has been a common aim in the photocatalyst industry. This study focuses on the development of an efficient, highly thermal and chemical stable, environmentally friendly and metal-free graphitic carbon nitride (g-C3N4) to overcome the problem of fast charge recombination which hinders photocatalytic performances. Nitrogen-doped carbon quantum dots (NCQDs) known for its high electronic and optical functionality properties is believed to achieve photocatalytic enhancement by efficient charge separation through forming heterogeneous interfaces. Hence, the current work focuses on the hybridisation of NCQDs and g-C3N4 to produce a composite photocatalyst for methylene blue (MB) degradation under LED light irradiation. The optimal hybridisation method and the mass loading required for maximum attainable MB degradation were systematically investigated. The optimum photocatalyst, 1 wt% NCQD/g-C3N4 composite was shown to exhibit a 2.6-fold increase in photocatalytic activity over bare g-C3N4. Moreover, the optimum sample displayed excellent stability and durability after three consecutive degradation cycles, retaining 91.2% of its original efficiency. Scavenging tests were also performed where reactive species, photon-hole (h+) was identified as the primary active species initiating the pollutant degradation mechanism. The findings of this study successfully shed light on the hybridisation methods of NCQDs which improve existing g-C3N4 photocatalyst systems for environmental remediation by utilising solar energy.

The suppression effect of dendritic cells maturation by adipose-derived stem cells through TGF-ß1 related pathway.

BACKGROUND: Our previous studies demonstrated that adipose-derived stem cells (ASCs) could modulate regulatory T cells (Treg) and prolong hind-limb allotransplant survival in vitro and in vivo. Dendritic cells (DCs) play a pivotal role in innate and adaptive immunity. The aim of this study is to investigate the underlying mechanism of ASCs in modulating DC maturation. MATERIALS AND METHODS: ASCs were isolated from rodent adipose tissue, DCs were derived from the bone marrow, and CD4+ T cells were purified from splenocytes. DCs were co-cultured with ASCs to evaluate the suppressive effects of ASCs. CD4+ T-cells were co-cultured with DCs pre-treated with or without ASCs. The cell surface markers of DCs were analyzed by flow cytometry. T-cell proliferation was analyzed by the BrdU proliferation test. Tolerogenic cytokines and indoleamine 2,3-dioxygenase (IDO) expressions after different treatments were detected by quantitative real-time PCR, Western blotting, and ELISA analysis. RESULT: ASCs suppressed DC maturation as evidenced by low expressions of CD80, CD86, and MHC-II. Also, ASC-treated mature DCs showed higher levels of TGF-ß1, IL-10, and IDO expressions, as compared to that in matured DCs (mDCs) alone. ASC-treated mDCs co-cultured with CD4+ T cells revealed a significant higher percentage of Treg than mDC without treatment. The IDO level in ASC-treated mDCs and Treg induction effects were blocked by the ASCs pre-treated with TGF-ß1 siRNAs, but not IL-10 siRNAs. CONCLUSION: ASC-modulated DC maturation correlated with TGF-ß1 secretion, IDO expression, and Treg induction. ASCs could be used as a potential immunomodulatory strategy for clinical application in allotransplantation.

The Ethics of Hand Transplantation: A Systematic Review.

PURPOSE: We conducted a systematic review to document ethical concerns regarding human upper extremity (UE) allotransplantation and how these concerns have changed over time. METHODS: We performed a systematic review of 5 databases to find manuscripts addressing ethical concerns related to UE allotransplantation. Inclusion criteria were papers that were on the topic of UE allotransplantation, and related ethical concerns, written in English. We extracted and categorized ethical themes under the 4 principles of bioethics: Autonomy, Beneficence, Nonmaleficence, and Justice. We assessed theme frequency by publication year using Joinpoint regression, analyzing temporal trends, and estimating annual percent change. RESULTS: We identified 474 citations; 49 articles were included in the final analysis. Publication years were 1998 to 2015 (mean, 3 publications/y; range, 0-7 publications/y). Nonmaleficence was most often addressed (46 of 49 papers; 94%) followed by autonomy (36 of 49; 74%), beneficence (35 of 49; 71%), and justice (31 of 49; 63%). Of the 14 most common themes, only "Need for More Research/Data" (nonmaleficence) demonstrated a significant increase from 1998 to 2002. CONCLUSIONS: Upper extremity transplantation is an appealing reconstructive option for patients and physicians. Its life-enhancing (vs life-saving) nature and requirement for long-term immunosuppression have generated much ethical debate. Availability of human data has influenced ethical concerns over time. Our results indicate that discussion of ethical issues in the literature increased following publication of UE transplants and outcomes as well as after meetings of national societies and policy decisions by regulatory agencies. CLINICAL RELEVANCE: Because UE transplantation is not a life-saving procedure, much ethical debate has accompanied its evolution. It is important for UE surgeons considering referring patients for evaluation to be aware of this discussion to fully educate patients and help them make informed treatment decisions.

From Auto- to Allotransplantation: Immunomodulatory Protocol for Hand and Arm Transplantation.

AIM: To achieve a favorable risk-benefit balance for hand transplantation, an immunomodulatory protocol was developed in the laboratory and translated to clinical application. METHODS: Following donor bone marrow infusion into transplant recipients, hand and arm allografts have been maintained on low-dose tacrolimus monotherapy. RESULTS: Good-to-excellent functional recovery has been achieved in patients compliant with medication and therapy, thus restoring autonomous and productive lives. CONCLUSION: The risk-benefit balance can be tilted in favor of the hand transplant recipients by using an immunomodulatory protocol with minimum immunosuppression.

A Novel Rodent Orthotopic Forelimb Transplantation Model That Allows for Reliable Assessment of Functional Recovery Resulting From Nerve Regeneration.

Improved nerve regeneration and functional outcomes would greatly enhance the utility of vascularized composite allotransplantation (VCA) such as hand and upper extremity transplantation. However, research aimed at achieving this goal has been limited by the lack of a functional VCA animal model. We have developed a novel rat midhumeral forelimb transplant model that allows for the characterization of upper extremity functional recovery following transplantation. At the final end point of 12 weeks, we found that animals with forelimb transplantation including median, ulnar and radial nerve coaptation demonstrated significantly improved grip strength and forelimb function as compared to forelimb transplantation without nerve approximation (grip strength: 1.71N ± 0.57 vs. no appreciable recovery; IBB scale: 2.6 ± 0.7? vs. 0.8 ± 0.40; p = 0.0005), and similar recovery to nerve transection-and-repair only (grip strength: 1.71N ± 0.57 vs. 2.03 ± 0.42.6; IBB scale: 2.6 ± 0.7 vs. 2.8 ± 0.8; p = ns). Moreover, all forelimb transplant animals with nerve coaptation displayed robust axonal regeneration with myelination and reduced flexor muscle atrophy when compared to forelimb transplant animals without nerve coaptation. In conclusion, this is the first VCA small-animal model that allows for reliable and reproducible measurement of behavioral functional recovery in addition to histologic evaluation of nerve regeneration and graft reinnervation.

Penile Allotransplantation for Complex Genitourinary Reconstruction.

PURPOSE: Reconstruction of complex functional structures is increasingly being performed with vascularized composite allotransplantation. Penile transplantation is a novel vascularized composite allotransplantation treatment option for severe penile tissue loss and disfigurement. Three allogeneic human penile transplantations have been reported. We review these cases as well as penile transplant indications, preclinical models and immunosuppression therapy. MATERIALS AND METHODS: We performed a comprehensive literature review for the years 1970 to 2016 via MEDLINE®, PubMed® and Google with the key words "penis transplantation," "penile rejection," "penile replantation," "penile tissue loss" and "penis vascularized composite allotransplantation." Relevant articles, including original research, reviews and nonscientific press reports, were selected based on contents, and a review of this literature was generated. RESULTS: Three human allogeneic penile transplantations have been performed to date, of which 1 was removed 14 days after transplantation. The second recipient reports natural spontaneous erections and impregnating his partner. All 3 patients were able to void spontaneously through the graft's urethra. The complexity of the transplant is determined by how proximally the penile shaft anastomosis is performed and additional pelvic tissue may be transplanted en bloc if needed. CONCLUSIONS: Penile transplantation is a technically demanding procedure with significant ethical and psychosocial implications that can provide tissue and functional replacement, including urinary diversion and natural erections. It is unclear how rejection and immunosuppression may affect graft function. Better models and more preclinical research are needed to better understand and optimize penile transplantation.

Blood product utilization in human upper-extremity transplantation: challenges, complications, considerations, and transfusion protocol conception.

BACKGROUND: Upper-extremity transplantation (UET) is a reality. Immunologic, functional, and graft survival outcomes have been encouraging. However, these complex reconstructions have unique considerations that pose distinct challenges. Transplant programs have reported morbidity and mortality due to significant intraoperative blood losses, but similar data are scant during other phases of recovery. We report experience from two centers on complete blood component demands and utilization with UET. STUDY DESIGN AND METHODS: Inpatient medical records of UET recipients from intraoperative (time from initiation of transplant surgery to exit from the operative suite) and postoperative (exit from the operative suite to discharge from the hospital) phases were retrospectively reviewed. RESULTS: Six patients received various UETs and mean (±SD) postoperative hospital stay was 46 (±14.4) days. Mean (±SD) intraoperative blood unit utilization was 14.8 (±10.2) red blood cells (RBCs), 10.5 (±11.8) plasma, 0.8 (±1.2) platelets (PLTs), and 0.3 (±0.8) cryoprecipitate units. Mean postoperative blood unit utilization was 9.3 (±10.4) RBCs, 5.3 (±6.7) plasma, 1.2 (±2.0) PLTs, and 0.7 (±1.6) cryoprecipitate units. Both intraoperative and postoperative blood utilization for unilateral versus bilateral transplant were different, but not significantly so. However, total inpatient blood use in bilateral transplants was significantly greater than in unilateral transplants. CONCLUSION: Substantial blood loss may occur in UET and require transfusion of many blood components, primarily RBCs and plasma. We propose an UET transfusion protocol and suggest that centers preparing to perform these transplants should actively engage the transfusion medicine service to ensure availability and access to appropriate blood components for the entire hospitalizations of these unique patients.

Outcomes after hand and upper extremity transplantation.

Hand and upper extremity transplantation (HUET) has emerged as the most frequently performed reconstructive procedure in the burgeoning field of vascularized composite allotransplantation (VCA). VCA refers to a form of transplant with multiple tissue types that represents a viable treatment option for devastating injuries where conventional reconstruction would be unable to restore form and function. As hand transplantation becomes increasingly more common, discussions on advantages and disadvantages of the procedure seem to intensify. Despite encouraging functional outcomes, current immunosuppressive regimens with their deleterious side-effect profile remain a major concern for a life-changing but not life-saving type of transplant. In addition, a growing number of recipients with progressively longer follow-up prompt the need to investigate potential long-term sequelae, such as chronic rejection. This review will discuss the current state of HUET, summarizing outcome data on graft survival, motor and sensory function, as well as immunosuppressive treatment. The implications of these findings for VCA in terms of achievements and challenges ahead will then be discussed.

Vascular Endothelial Growth Factor Induction of Muscle-Derived Stem Cells Enhances Vascular Phenotype While Preserving Myogenic Potential.

BACKGROUND: Previous work by our group and other laboratories have revealed that muscle-derived stem cells (MDSCs) may contain both myogenic and endothelial progenitors, making MDSCs a promising option for skeletal muscle regeneration. The purpose of this study was to investigate the impact of vascular endothelial growth factor (VEGF) induction on the vascular and myogenic potential of MDSCs. METHODS: Muscle-derived stem cells were isolated from 4- to 8-week-old C57BL/6J mice using a preplate technique and recombinant human VEGFa was used as the induction agent. Cellular proliferation and migration were assessed using serial imaging and wound healing assays, respectively. Myosin heavy chain staining was performed to assess MDSC myotube formation. Vascular potential of MDSCs was measured by expression of CD31 and in vitro capillary tube formation. RESULTS: Vascular endothelial growth factor stimulation led to a dose-dependent increase in MDSC proliferation (P < 0.05) and migration kinetics (P < 0.01). Control MDSCs had low levels of baseline expression of CD31, which was significantly upregulated by VEGF stimulation. Similarly, MDSCs demonstrated a basal capability for capillary tube formation, which was significantly increased after VEGF induction as evidenced by increased branches (5.91 ± 0.58 vs 9.23 ± 0.67, P < 0.01) and total tube length (11.73 ± 0.97 vs 18.62 ± 1.57 mm, P < 0.01). Additionally, the myogenic potential of MDSCs as measured by fusion index remained unchanged with increasing concentration of VEGF up to 250 ng/mL (P = 0.77). CONCLUSIONS: Vascular endothelial growth factor induction enhances MDSC proliferation, migration, and endothelial phenotypes without negatively impacting myogenic potential. These results suggest that VEGF stimulation may improve vascularization of MDSC-based strategies for skeletal muscle regeneration.

Hand Transplantation: Evolution of a Personal Outlook.

The field of vascularized composite allotransplantation-combining advances in reconstructive surgery, transplantation, and immunology-offers great promise for patients with heretofore unsolvable problems. In the last 30 years, hand transplantation has progressed through the phases of being a research subject, a controversial clinical procedure, a more widely accepted and expanding field, and now a promising endeavor undergoing refined indications. Although many lessons have been learned, few procedures in the author's experience have been as life-transformative in restoring the body image, motor and sensory functions, activities of daily living, and personal autonomy as successful hand transplantation.

Two-dimensional bismuth oxybromide coupled with molybdenum disulphide for enhanced dye degradation using low power energy-saving light bulb.

In the present work, two-dimensional bismuth oxybromide (BiOBr) was synthesized and coupled with co-catalyst molybdenum disulphide (MoS2) via a simple hydrothermal process. The photoactivity of the resulting hybrid photocatalyst (MoS2/BiOBr) was evaluated under the irradiation of 15 W energy-saving light bulb at ambient condition using Reactive Black 5 (RB5) as model dye solution. The photo-degradation of RB5 by BiOBr loaded with 0.2 wt% MoS2 (MoBi-2) exhibited more than 1.4 and 5.0 folds of enhancement over pristine BiOBr and titanium dioxide (Degussa, P25), respectively. The increased photocatalytic performance was a result of an efficient migration of excited electrons from BiOBr to MoS2, prolonging the electron-hole pairs recombination rate. A possible charge transfer diagram of this hybrid composite photocatalyst, and the reaction mechanism for the photodegradation of RB5 were proposed.

Combined Anti-CD154/CTLA4Ig Costimulation Blockade-Based Therapy Induces Donor-Specific Tolerance to Vascularized Osteomyocutaneous Allografts.

Tolerance induction by means of costimulation blockade has been successfully applied in solid organ transplantation; however, its efficacy in vascularized composite allotransplantation, containing a vascularized bone marrow component and thus a constant source of donor-derived stem cells, remains poorly explored. In this study, osteomyocutaneous allografts (alloOMCs) from Balb/c (H2(d) ) mice were transplanted into C57BL/6 (H2(b) ) recipients. Immunosuppression consisted of 1 mg anti-CD154 on day 0, 0.5 mg CTLA4Ig on day 2 and rapamycin (RPM; 3 mg/kg per day from days 0-7, then every other day for 3 weeks). Long-term allograft survival, donor-specific tolerance and donor-recipient cell trafficking were evaluated. Treatment with costimulation blockade plus RPM resulted in long-term graft survival (>120 days) of alloOMC in 12 of 15 recipients compared with untreated controls (median survival time [MST] ≈10.2 ± 0.8 days), RPM alone (MST ≈33 ± 5.5 days) and costimulation blockade alone (MST ≈45.8 ± 7.1 days). Donor-specific hyporesponsiveness in recipients with viable grafts was demonstrated in vitro. Evidence of donor-specific tolerance was further assessed in vivo by secondary donor-specific skin graft survival and third-party graft rejection. A significant increase of Foxp3(+) regulatory T cells was evident in tolerant animals. Donor cells populated peripheral blood, thymus, and both donor and recipient bone marrow. Consequently, combined anti-CD154/CTLA4Ig costimulation blockade-based therapy induces donor-specific tolerance in a stringent murine alloOMC transplant model.

Spontaneous resolution of acute rejection and tolerance induction with IL-2 fusion protein in vascularized composite allotransplantation.

Vascularized composite allotransplantation (VCA) has emerged as a treatment option for treating nonlife-threatening conditions. Therefore, in order to make VCA a safe reconstruction option, there is a need to minimize immunosuppression, develop tolerance-inducing strategies and elucidate the mechanisms of VCA rejection and tolerance. In this study we explored the effects of hIL-2/Fc (a long-lasting human IL-2 fusion protein), in combination with antilymphocyte serum (ALS) and short-term cyclosporine A (CsA), on graft survival, regulatory T cell (Treg) proliferation and tolerance induction in a rat hind-limb transplant model. We demonstrate that hIL-2/Fc therapy tips the immune balance, increasing Treg proliferation and suppressing effector T cells, and permits VCA tolerance as demonstrated by long-term allograft survival and donor-antigen acceptance. Moreover, we observe two distinct types of acute rejection (AR), progressive and reversible, within hIL-2/Fc plus ALS and CsA treated recipients. Our study shows differential gene expression profiles of FoxP3 versus GzmB, Prf1 or interferon-γ in these two types of AR, with reversible rejection demonstrating higher Treg to Teff gene expression. This correlation of gene expression profile at the first clinical sign of AR with VCA outcomes can provide the basis for further inquiry into the mechanistic aspects of VCA rejection and future drug targets.

Mouse Models of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder characterized by synovitis that leads to cartilage and bone erosion by invading fibrovascular tissue. Mouse models of RA recapitulate many features of the human disease. Despite the availability of medicines that are highly effective in many patient populations, autoimmune diseases (including RA) remain an area of active biomedical research, and consequently mouse models of RA are still extensively used for mechanistic studies and validation of therapeutic targets. This review aims to integrate morphologic features with model biology and cover the key characteristics of the most commonly used induced and spontaneous mouse models of RA. Induced models emphasized in this review include collagen-induced arthritis and antibody-induced arthritis. Collagen-induced arthritis is an example of an active immunization strategy, whereas antibody- induced arthritis models, such as collagen antibody-induced arthritis and K/BxN antibody transfer arthritis, represent examples of passive immunization strategies. The coverage of spontaneous models in this review is focused on the TNFΔ (ARE) mouse, in which arthritis results from overexpression of TNF-α, a master proinflammatory cytokine that drives disease in many patients.