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The identity and origin of the stem/progenitor cells for adult joint cartilage repair remain unknown, impeding therapeutic development. Simulating the common therapeutic modality for cartilage repair in humans, i.e., full-thickness microfracture joint surgery, we combined the mouse full-thickness injury model with lineage tracing and identified a distinct skeletal progenitor cell type enabling long-term (beyond 7 days after injury) articular cartilage repair in vivo. Deriving from a population with active Prg4 expression in adulthood while lacking aggrecan expression, these progenitors proliferate, differentiate to express aggrecan and type II collagen, and predominate in long-term articular cartilage wounds, where they represent the principal repair progenitors in situ under native repair conditions without cellular transplantation. They originate outside the adult bone marrow or superficial zone articular cartilage. These findings have implications for skeletal biology and regenerative medicine for joint injury repair.

Collapsing foot deformity (CFD) and its resulting sequelae caused by recurring talotarsal joint dislocation (RTTJD) affects pediatric and adult patients. An extraosseous talotarsal stabilization (EOTTS) procedure, a subset of subtalar arthroereisis (SA) procedures, is recommended as a minimally invasive, first in-line surgical treatment option for CFD. The aim of this multicenter, retrospective study was to evaluate patient-reported outcomes measures in patients who were treated for RTTJD with Type II EOTTS implants. Sixty-seven cases having a median age of 38 years (range: 10-74) with more than 5 years of follow-up were included in this study. The mean postoperative visual analog scale and Maryland Foot Score was 1.0 ± 1.9 and 92.3 ± 11.3, respectively, indicating excellent clinical outcomes. Subjectively, 88% cases reported as being satisfied with the outcome, 94% cases said they would recommend EOTTS, and 93% said that, if necessary, they would repeat it on their contralateral foot. A subgroup analysis revealed that while not statistically significant, clinical outcomes were slightly better in pediatric patients compared to adults. Implant removal rate was 4.5% (3 cases), and these were in the adult group only. Rate of minor issues such as pain, stiffness, discomfort, etc. was 15%; however, no serious adverse effects or complications were observed in any patient. This study suggests that EOTTS is an effective surgical treatment option wherein successful long-term clinical outcomes with low failure rates can be achieved in a select patient population., (Copyright © 2023 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

For behavior analytic practitioners, skills related to building a therapeutic alliance (e.g., empathic statements, reflective listening, affirmations) may be as important as knowledge of and skills in implementation of the science of behavior analysis. We surveyed 277 board certified behavior analysts (BCBAs) to learn more about their training, use of these skills, and their perceptions of how their skills might have changed over years of practicing. The findings suggest that behavior analysts may benefit from explicit training in skills required to establish and maintain therapeutic relationships with parents of children with autism. In this article we review recent research in this area and suggest directions for training of behavior analysts. Further, motivational interviewing is introduced as an evidence-based clinical approach that encompasses many of the skills required to build a therapeutic alliance., Competing Interests: Conflicts of Interest/Competing InterestsN/A., (© Association for Behavior Analysis International 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Blood samples are required in most experimental animal designs to assess various hematological parameters. This paper presents two procedures for blood collection in rats: the lateral tail vein puncture and the dorsal penile vein puncture, which offer significant advantages over other previously described techniques. This study shows that these two procedures allow for fast sampling (under 10 min) and yield sufficient blood volumes for most assays (202 μL ± 67.7 μL). The dorsal penile vein puncture must be done under anesthesia, whereas the lateral tail vein puncture can be done on a conscious, restrained animal. Alternating these two techniques, therefore, enables blood draw in any situation. While it is always recommended for an operator to be assisted during a procedure to ensure animal welfare, these techniques require only a single operator, unlike most blood sampling methods that require two. Moreover, whereas these previously described methods (e.g., jugular stick, subclavian vein blood draw) require extensive prior training to avoid harm to or death of the animal, tail vein and dorsal penile vein puncture are rarely fatal. For all these reasons, and according to the context (e.g., for studies including male rats, during the perioperative or immediate postoperative period, for animals with thin tail veins), both techniques can be used alternately to enable repeated blood draws.

Background:  For 50 years, static cold storage (SCS) has been the gold standard for solid organ preservation in transplantation. Although logistically convenient, this preservation method presents important constraints in terms of duration and cold ischemia-induced lesions. We aimed to develop a machine perfusion (MP) protocol for recovery of vascularized composite allografts (VCA) after static cold preservation and determine its effects in a rat limb transplantation model., Methods:  Partial hindlimbs were procured from Lewis rats and subjected to SCS in Histidine-Tryptophan-Ketoglutarate solution for 0, 12, 18, 24, and 48 hours. They were then either transplanted (Txp), subjected to subnormothermic machine perfusion (SNMP) for 3 hours with a modified Steen solution, or to SNMP + Txp. Perfusion parameters were assessed for blood gas and electrolytes measurement, and flow rate and arterial pressures were monitored continuously. Histology was assessed at the end of perfusion. For select SCS durations, graft survival and clinical outcomes after transplantation were compared between groups at 21 days., Results:  Transplantation of limbs preserved for 0, 12, 18, and 24-hour SCS resulted in similar survival rates at postoperative day 21. Grafts cold-stored for 48 hours presented delayed graft failure ( p  = 0.0032). SNMP of limbs after 12-hour SCS recovered the vascular resistance, potassium, and lactate levels to values similar to limbs that were not subjected to SCS. However, 18-hour SCS grafts developed significant edema during SNMP recovery. Transplantation of grafts that had undergone a mixed preservation method (12-hour SCS + SNMP + Txp) resulted in better clinical outcomes based on skin clinical scores at day 21 post-transplantation when compared to the SCS + Txp group ( p  = 0.01613)., Conclusion:  To date, VCA MP is still limited to animal models and no protocols are yet developed for graft recovery. Our study suggests that ex vivo SNMP could help increase the preservation duration and limit cold ischemia-induced injury in VCA transplantation., Competing Interests: The authors declare competing interests. Drs. A.G.L., C.L.C., K.U., S.N.T., R.J.d.V., and C.A.P. have provisional patent applications relevant to this study. K.U. and S.N.T. have financial interests in Sylvatica Biotech Inc., a company focused on developing organ preservation technology. All competing interests are managed by Mass General Brigham in accordance with their conflict-of-interest policies., (Thieme. All rights reserved.)

Objectives: Many autistic children exhibit challenging and disruptive behaviors that can present challenges for both children and their families by interfering with acquisition of adaptive skills and affecting family and peer relationships. Behavioral parent training (BPT) is an evidence-based approach to reducing autistic children's disruptive behavior, but many families face a number of barriers to accessing BPT, such as availability of BPT in their community, and transportation and scheduling challenges. Therefore, we sought to explore the feasibility and promise of effectiveness of adapting an established BPT program to a telehealth format during the COVID-19 pandemic., Methods: A feasibility trial of BPT via telehealth was conducted with fourteen parents of autistic children., Results: Parents and clinicians were able to implement BPT via telehealth with a high degree of fidelity, and parents rated both BPT and the telehealth format favorably. The program also showed promise of effectiveness in reducing autistic children's disruptive behavior, improving their adaptive skills, as well as reducing parents' stress, and improving parents' sense of parenting competence., Conclusions: The findings replicate and extend findings from previous studies, further demonstrating the promise of telehealth as a viable alternative format for delivering BPT. We also explore implications for future research, including the opportunity for more thorough evaluation of the effectiveness of BPT via telehealth., Competing Interests: Conflict of InterestThe first, second, fourth, and fifth authors are employed by organizations that deliver services based on the science of applied behavior analysis for individuals with disabilities, and the third author maintains a faculty position within a graduate program for applied behavior analysis. There are no other potential conflicts of interest to report., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Purpose: Miniature linguistic systems (also known as matrix training) is a method of organizing learning targets to achieve generative learning or recombinative generalization. This systematic review is aimed at determining whether matrix training is effective for individuals with autism spectrum disorder (ASD) in terms of improving recombinative generalization for instruction-following, expressive language, play skills, and literacy skills., Method: A systematic review methodology was employed to limit bias in the various review stages. A multifaceted search was conducted. Potential primary studies were imported into Covidence, a systematic review software, and inclusion criteria were applied. Data were extracted regarding (a) participant characteristics, (b) matrix designs, (c) intervention methods, and (d) dependent variable. A quality appraisal using the What Works Clearinghouse (WWC) Single-Case Design Standards (Version 1.0, Pilot) was carried out. In addition to the visual analysis of the data, an effect size estimate, non-overlap of all pairs (NAP), was generated for each participant. Independent t tests and between-subjects analyses of variance were conducted to identify moderators of effectiveness., Results: Twenty-six studies including 65 participants met criteria for inclusion. All included studies were single-case experimental designs. Eighteen studies received a rating of Meets Standards Without Reservations or Meets Standards With Reservations . The aggregated combined NAP scores for acquisition, recombinative generalization, and maintenance of a range of outcomes were in the high range., Conclusions: Findings suggested that matrix training is an effective teaching method for individuals with ASD for acquisition, recombinative generalization, and maintenance of a range of outcomes. Statistical analyses to identify moderators of effectiveness were insignificant. Based on the WWC Single-Case Design Standards matrix training meets criteria to be considered an evidence-based practice for individuals with ASD.

Background: The standard in nipple reconstruction remains the autologous skin flap. Unfortunately, the results are not satisfying, with up to 75% loss of nipple projection over time. Existing studies investigated the use of primates as a source of implants. The authors hypothesized that the porcine nipple can serve as a perfect shape-supporting implant because of functional similarities to the human nipple. A decellularization protocol was developed to obtain an acellular nipple scaffold (ANS) for nipple reconstruction., Methods: Tissue samples were collected from eight disease-free female Yorkshire pigs (60 to 70 kg) and then decellularized. The decellularization efficiency and extracellular matrix characterization was performed histologically and quantitatively (DNA, total collagen, elastin, and glycosaminoglycan content). In vitro and in vivo biocompatibility was determined by human dermal fibroblast culture and subcutaneous implantation of six ANSs in a single Yorkshire pig (60 to 70 kg), respectively. Inflammation and adverse events were monitored daily based on local clinical signs., Results: The authors showed that all cellular structures and 96% of DNA [321.7 ± 57.6 ng DNA/mg wet tissue versus 11.7 ± 10.9 ng DNA/mg wet tissue, in native and ANS, respectively ( P < 0.001)] can be successfully removed. However, this was associated with a decrease in collagen [89.0 ± 11.4 and 58.8 ± 9.6 μg collagen/mg ( P < 0.001)] and elastin [14.2 ± 1.6 and 7.9 ± 2.4 μg elastin/mg ( P < 0.05)] and an increase in glycosaminoglycan content [5.0 ± 0.7 and 6.0 ± 0.8 ng/mg ( P < 0.05)]. ANS can support continuous cell growth in vitro and during preliminary biocompatibility tests in vivo., Conclusion: This is a preliminary report of a novel promising ANS for nipple reconstruction, but more research is needed to validate results., Clinical Relevance Statement: Breast cancer is very common among women. Treatment involves mastectomy, but its consequences affect patient mental well-being, and can lead to depression. Nipple-areola complex reconstruction is critical, and existing methods lead to unsatisfactory outcomes., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background . There have been few advances in technique since vascular anastomosis was performed with silk suture on a curved needle in 1902. This technique results in disruption of the endothelium with exposed intraluminal suture, both of which may lead to thrombocyte aggregation, intimal hyperplasia, and vascular stenosis. A variety of alternative techniques have been explored, with limited success. Photochemical tissue bonding (PTB) is a light-activated methodology of rapidly cross-linking tissue interfaces at the molecular level. Herein, we describe a new technique for anastomosis of venous interposition graft in an ovine model of femoral artery bypass utilizing PTB. Methods . Polypay specific pathogen free sheep (n = 5; 40-45 kg) underwent femoral artery bypass utilizing saphenous vein. The femoral artery was transected and reversed saphenous vein was implanted as an interposition graft. The proximal anastomosis was created as a vein-over-artery cuff utilizing PTB, and the distal anastomosis was created with standard interrupted 8-0 polypropylene suture. Four weeks post-index operation, femoral angiogram was performed to evaluate patency, tortuosity, and luminal diameter. All bypass grafts were harvested and longitudinal and transverse histological sections from the proximal anastomosis were analyzed. Results . The PTB anastomoses (n = 5) were immediately watertight and patent. All animals survived the 28-day study duration. Angiography revealed patent grafts with no aneurysm or stenosis (n = 5). Histologic examination revealed integration of the venous endothelium with the arterial adventitia. Conclusion . Photochemical tissue bonding creates an immediate strong, watertight vascular anastomosis that can withstand physiologic arterial pressure and remains patent at 28 days without the need for intraluminal suture.

Introduction: Multiple perfusion systems have been investigated on vascularized composite allografts, with various temperatures and different preservation solutions, most using continuous flow (CF). However, physiological flow is pulsatile and provides better outcomes in kidney and lung ex vivo perfusions. The objective of this pilot study is to compare pulsatile flow (PF) with CF in our 24-h subnormothermic machine perfusion protocol for swine hindlimbs., Methods: Partial hindlimbs were harvested from Yorkshire pigs and perfused with a modified Steen solution at 21°C for 24 h either with CF (n = 3) or with pulsatile flow (PF) at 60 beats/min (n = 3). Perfusion parameters, endothelial markers, and muscle biopsies were assessed at different timepoints., Results: Overall, lactate levels were significantly lower in the PF group (P = 0.001). Glucose uptake and potassium concentration were similar in both groups throughout perfusion. Total nitric oxide levels were significantly higher in the PF group throughout perfusion (P = 0.032). Nitric oxide/endothelin-1 ratio also tends to be higher in the PF group, reflecting a potentially better vasoconductivity with PF, although not reaching statistical significance (P = 0.095). Arterial resistances were higher in the PF group (P < 0.001). Histological assessment did not show significant difference in muscular injury between the two groups. Weight increased quicker in the CF group but reached similar values with the PF after 24 h., Conclusions: This pilot study suggests that PF may provide superior preservation of vascularized composite allografts when perfused for 24 h at subnormothermic temperatures, with potential improvement in endothelial function and decreased ischemic injury., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Tissue engineering of skin and mucosa is essential for the esthetic and functional reconstruction of individuals disfigured by trauma, resection surgery, or severe burns while overcoming the limited amount of autograft and donor site morbidity., Purpose: We aimed to determine whether a combination of Gelatin-methacryloyl (GelMA) hydrogel scaffold alone or loaded with either dental pulp stem cells (DPSCs) and/or vascular endothelial growth factor (VEGF) could improve skin wound healing in rats., Materials and Methods: Four 10 mm full-thickness skin defects were created on the dorsum of 15 Sprague-Dawley rats. The wounds were treated with GelMA alone, GelMA+DPSCs, or GelMA+DPSCs+VEGF. Unprotected wounds were used as controls. Animals were euthanized at 1-, 2-, and 4 weeks post-surgery, and the healing wounds were harvested for clinical, histological, and RT-PCR analysis., Results: No signs of clinical inflammation were observed among all groups. Few and sparse mononuclear inflammatory cells were observed in GelMA+DPSCs and GelMA+DPSCs+VEGF groups at 2 weeks, with complete epithelialization of the wounds. At 4 weeks, the epidermis in GelMA+DPSCs and GelMA+DPSCs+VEGF groups was indistinguishable from the empty defect and GelMA groups. The decrease in cellularity and increase in density of collagen fibers were observed over time in both GelMA+DPSCs and GelMA+DPSCs+VEGF groups but were more evident in the GelMA+DPSCs+VEGF group. The GelMA+DPSCs+VEGF group showed a higher expression of the KER 10 gene at all time points compared with the other groups. Expression of Col1 A1 and TGFβ-1 were not statistically different over time neither among the groups., Conclusion: GelMA scaffolds loaded with DPSCs, and VEGF accelerated the re-epithelialization of skin wounds., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Fasciocutaneous flaps (FCF) have become the gold standard for complex defect reconstruction in plastic and reconstructive surgery. This muscle-sparing technique allows transferring vascularized tissues to cover any large defect. FCF can be used as pedicled flaps or as free flaps; however, in the literature, failure rates for pedicled FCF and free FCF are above 5%, leaving room for improvement for these techniques and further knowledge expansion in this area. Ischemic preconditioning (I.P.) has been widely studied, but the mechanisms and the optimization of the I.P. regimen are yet to be determined. This phenomenon is indeed poorly explored in plastic and reconstructive surgery. Here, a surgical model is presented to study the I.P. regimen in a rat axial fasciocutaneous flap model, describing how to safely and reliably assess the effects of I.P. on flap survival. This article describes the complete surgical procedure, including suggestions to improve the reliability of this model. The objective is to provide researchers with a reproducible and reliable model to test various ischemic preconditioning regimens and assess their effects on flap survivability.

Background: Facioscapulohumeral muscular dystrophy (FSHD) is a progressive myopathy caused by misexpression of the double homeobox 4 (DUX4) embryonic transcription factor in skeletal muscle. Identifying quantitative and minimally invasive FSHD biomarkers to report on DUX4 activity will significantly accelerate therapeutic development., Objective: The goal of this study was to analyze secreted proteins known to be induced by DUX4 using the commercially available Olink Proteomics platform in order to identify potential blood-based molecular FSHD biomarkers., Methods: We used high-throughput, multiplex immunoassays from Olink Proteomics to measure the levels of several known DUX4-induced genes in a cellular myoblast model of FSHD, in FSHD patient-derived myotube cell cultures, and in serum from individuals with FSHD. Levels of other proteins on the Olink Proteomics panels containing these DUX4 targets were also examined in secondary exploratory analysis., Results: Placental alkaline phosphatase (ALPP) levels correlated with DUX4 expression in both cell-based FSHD systems but did not distinguish FSHD patient serum from unaffected controls., Conclusions: ALPP, as measured with the Olink Proteomics platform, is not a promising FSHD serum biomarker candidate but could be utilized to evaluate DUX4 activity in discovery research efforts.

As a field that predominately supports individuals with autism spectrum disorder (ASD), we have an ethical duty as behavior analysts to ensure that the goals we write and interventions we prescribe promote best outcomes across the lifespan. This is critical, given that as it stands now, outcomes in adulthood for individuals with ASD are poor in every area assessed. The Ethics Code for Behavior Analysts can be interpreted to provide support for teaching the right goals, the right way, with respect to inherent rights of those we serve, in order to help affect positive changes in these outcomes. The present article highlights ethical themes that are relevant in order to affect these changes that are supported by the Code , as well as actionable steps to take next. The aim is to provide a resource for practitioners to use in clinical practice and in making ethical decisions that will help to improve outcomes for individuals with autism in adulthood. In addition, recommendations are made about integrating these values and approaches in terms of training, supervision, advocacy, and research., Competing Interests: Conflicts of Interest/Competing InterestsThe authors have no conflicts of interest to declare that are relevant to the content of this article. Additional declarations related to ethics/consent are not applicable, because this article did not involve the use of human and/or animal participants., (© Association for Behavior Analysis International 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Matrix training consists of arranging targets for instruction to promote fine-grained stimulus control resulting in the establishment of skills without direct training. Recent reviews of the matrix training literature (Curiel et al., 2020a, b.; Kemmerer et al., 2021) highlighted the efficacy and efficiency of the approach with learners with and without disabilities. These reviews noted substantial variations in procedures across studies, suggesting the approach may be flexibly deployed across content areas and teaching procedures. This outcome is positive for practitioners as they may customize matrix training to meet the unique needs of their clients. However, it also necessitates decision making to sort through the variations in the literature. This tutorial was developed to help practitioners weigh various considerations when using matrix training. Tools and resources are provided to illustrate and accelerate adoption into practice settings., Supplementary Information: The online version contains supplementary material available at 10.1007/s40617-022-00733-5., Competing Interests: Conflicts of InterestWe have no conflicts of interest relevant to this article to disclose., (© Association for Behavior Analysis International 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Vascularized composite allografts (VCAs) allow reconstruction of devastating injuries and amputations, yet require lifelong immunosuppression that is associated with significant morbidity. Induction of immune tolerance of VCAs would permit widespread use of these procedures. VCAs are acquired from deceased donors most likely to be fully -MHC-mismatched (in contrast to living-related renal transplant donor-recipient pairs matched at one MHC haplotype). After achieving VCA tolerance in a swine model equivalent to clinical living-related renal transplants (single-haplotype MHC mismatches: e.g., "mother-daughter"/haploidentical), we tested our protocol in MHC class I, class II, and fully-MHC-mismatched pairs. Although class II mismatched swine demonstrated similar results as the haploidentical scenario (stable mixed chimerism and tolerance), our protocol failed to prevent rejection of class I and full mismatch VCAs. Here, we describe a new adapted conditioning protocol that successfully achieved tolerance across MHC class-I-mismatch barriers in swine., Methods: Swine were treated with non-myeloablative total body and thymic irradiation two days prior to infusion of bone marrow cells from an MHC class I-mismatched donor. They also received a short-term treatment with CTLA4-Ig (Belatacept ® ) and anti-IL6R mAb (Tociluzimab ® ) and were transplanted with an osteomyocutaneous VCA from the same donor., Results: Stable mixed chimerism and tolerance of MHC class-I-mismatched VCAs was achieved in 3 recipients. Allograft tolerance was associated with a sustained lack of anti-donor T cell response and a concomitant expansion of double negative CD4 - CD8 - T cells producing IL-10., Conclusions: This study demonstrates the first successful mixed chimerism-induced VCA tolerance in a large animal model across a MHC class-I-mismatch. Future studies aimed at fully-mismatched donor-recipient pairs are under investigation with this protocol., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lellouch, Andrews, Saviane, Ng, Schol, Goutard, Gama, Rosales, Colvin, Lantieri, Randolph, Benichou and Cetrulo.)

Vascularized Composite Allografts (VCA) such as hand, face, or penile transplant represents the cutting-edge treatment for devastating skin defects, failed by the first steps of the reconstructive ladder. Despite promising aesthetic and functional outcomes, the main limiting factor remains the need for a drastically applied lifelong immunosuppression and its well-known medical risks, preventing broader indications. Therefore, lifting the immune barrier in VCA is essential to tip the ethical scale and improve patients' quality of life using the most advanced surgical techniques. De novo creation of a patient-specific graft is the upcoming breakthrough in reconstructive transplantation. Using tissue engineering techniques, VCAs can be freed of donor cells and customized for the recipient through perfusion-decellularization-recellularization. To develop these new technologies, a large-scale animal VCA model is necessary. Hence, swine fascio-cutaneous flaps, composed of skin, fat, fascia, and vessels, represent an ideal model for preliminary studies in VCA. Nevertheless, most VCA models described in the literature include muscle and bone. This work reports a reliable and reproducible technique for saphenous fascio-cutaneous flap harvest in swine, a practical tool for various research fields, especially vascularized composite tissue engineering.

Neuroma is a common sequela of traumatic peripheral nerve injury that can result in pain and decreased quality of life for patients. Neuromas result from axonal outgrowth in an attempt to reestablish continuity with the disrupted distal nerve end. Photosealing is a light-activated technique whereby tissues can be securely isolated in a strong and secure manner. This study investigated whether photosealing of autologous vein and crosslinked human amniotic membrane (xHAM) to cap the proximal stump of transected sciatic nerve would prevent disorganized axonal regeneration and neuroma in a rat model., Methods: The right sciatic nerve of Lewis rats (n = 27, 300-350 g) was transected 1 cm proximal to the trifurcation. Animals were randomized to one of three groups (n = 9): no further intervention (Group 1), photosealing with xHAM (Group 2), or photosealing with vein (Group 3). After 60 days, rats were euthanized and their right hindlimbs were re-explored for evidence of disorganized axonal regeneration and/or bulbous neuroma., Results: All untreated control animals were found to have protruding nerve fibers, often invading the adjacent muscle, and 33% of these control animals exhibited a bulbous neuroma. Photosealing with xHAM successfully capped 100% of nerves, with no observable axonal outgrowth. Photosealing with vein prevented axonal outgrowth in eight of nine nerves. No bulbous neuroma was found in any photosealed nerves., Conclusion: Nerve capping with photosealed xHAM or autologous vein can prevent axonal outgrowth in transected nerves, therefore decreasing the likelihood of symptomatic neuroma formation following nerve transection injury or surgical intervention., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: Machine perfusion is gaining interest as an efficient method of tissue preservation of Vascularized Composite Allografts (VCA). The aim of this study was to develop a protocol for ex vivo subnormothermic oxygenated machine perfusion (SNMP) on rodent hindlimbs and to validate our protocol in a heterotopic hindlimb transplant model., Methods: In this optimization study we compared three different solutions during 6 h of SNMP (n = 4 per group). Ten control limbs were stored in a preservation solution on Static Cold Storage [SCS]). During SNMP we monitored arterial flowrate, lactate levels, and edema. After SNMP, muscle biopsies were taken for histology examination, and energy charge analysis. We validated the best perfusion protocol in a heterotopic limb transplantation model with 30-d follow up (n = 13). As controls, we transplanted untreated limbs (n = 5) and hindlimbs preserved with either 6 or 24 h of SCS (n = 4 and n = 5)., Results: During SNMP, arterial outflow increased, and lactate clearance decreased in all groups. Total edema was significantly lower in the HBOC-201 group compared to the BSA group (P = 0.005), 4.9 (4.3-6.1) versus 48.8 (39.1-53.2) percentage, but not to the BSA + PEG group (P = 0.19). Energy charge levels of SCS controls decreased 4-fold compared to limbs perfused with acellular oxygen carrier HBOC-201, 0.10 (0.07-0.17) versus 0.46 (0.42-0.49) respectively (P = 0.002)., Conclusions: Six hours ex vivo SNMP of rodent hindlimbs using an acellular oxygen carrier HBOC-201 results in superior tissue preservation compared to conventional SCS., (Copyright © 2021. Published by Elsevier Inc.)

Facioscapulohumeral muscular dystrophy (FSHD) is the second most common genetic myopathy, characterized by slowly progressing and highly heterogeneous muscle wasting with a typical onset in the late teens/early adulthood [1]. Although the etiology of the disease for both FSHD type 1 and type 2 has been attributed to gain-of-toxic function stemming from aberrant DUX4 expression, the exact pathogenic mechanisms involved in muscle wasting have yet to be elucidated [2-4]. The 2021 FSHD International Research Congress, held virtually on June 24-25, convened over 350 researchers and clinicians to share the most recent advances in the understanding of the disease mechanism, discuss the proliferation of interventional strategies and refinement of clinical outcome measures, including results from the ReDUX4 trial, a phase 2b clinical trial of losmapimod in FSHD [NCT04003974]., (© 2022. The Author(s).)

In Skinner's chapter titled The Ethics of Helping People , he stated, "By giving too much help, we postpone the acquisition of effective behavior and perpetuate the need for help" (Skinner, 1996, p. 63). Through years of living cross-culturally in various African countries, the first author has seen this demonstrated not only in organizations but also as part of the very fabric of society. The detrimental effects of helping, as described by Skinner, are especially evident in African countries that were formerly colonized and continue through the delivery of modern aid by western nations. Robust reinforcement contingencies surround the helper and the helped, which creates and maintains a reciprocal dominating/dependent relationship that has stifled growth in the past and continues to do so in the present. Considering that behavior analysis was born in the western world, any dissemination efforts to formerly colonized African countries will perpetuate the power dynamic conceived from colonial "helping" practices. In this paper, suggestions will be outlined for behavior analysts interested in international dissemination, specifically looking at the role of participatory community development in alleviating colonial relations between these regions., Competing Interests: Conflicts of interestWe have no known conflicts of interest to disclose., (© Association for Behavior Analysis International 2022.)

Bone metastases are devastating complications of cancer. They are particularly common in prostate cancer (PCa), represent incurable disease, and are refractory to immunotherapy. We seek to define distinct features of the bone marrow (BM) microenvironment by analyzing single cells from bone metastatic prostate tumors, involved BM, uninvolved BM, and BM from cancer-free, orthopedic patients, and healthy individuals. Metastatic PCa is associated with multifaceted immune distortion, specifically exhaustion of distinct T cell subsets, appearance of macrophages with states specific to PCa bone metastases. The chemokine CCL20 is notably overexpressed by myeloid cells, as is its cognate CCR6 receptor on T cells. Disruption of the CCL20-CCR6 axis in mice with syngeneic PCa bone metastases restores T cell reactivity and significantly prolongs animal survival. Comparative high-resolution analysis of PCa bone metastases shows a targeted approach for relieving local immunosuppression for therapeutic effect., Competing Interests: Declaration of interests P.V.K. serves on the Scientific Advisory Board to Celsius Therapeutics Inc. and Biomage Inc. D.T.S. is a director and shareholder for Agios Therapeutics and Editas Medicines; a founder, director, shareholder, and scientific advisory board member for Magenta Therapeutics and LifeVault Bio, a shareholder and founder of Fate Therapeutics, and a director, founder, and shareholder for Clear Creek Bio, a consultant for FOG Pharma and VCanBio, and a recipient of sponsored research funding from Novartis. D.B.S. is a founder, consultant, and shareholder for Clear Creek Bio., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Successful 3D scaffold designs for musculoskeletal tissue engineering necessitate full consideration of the form and function of the tissues of interest. When designing structures for engineering cartilage and osteochondral tissues, one must reconcile the need to develop a mechanically robust system that maintains the health of cells embedded in the scaffold. In this work, we present an approach that decouples the mechanical and biochemical needs and allows for the independent development of the structural and cellular niches in a scaffold. Using the highly tuned capabilities of digital light processing-based stereolithography, structures with complex architectures are achieved over a range of effective porosities and moduli. The 3D printed structure is infilled with mesenchymal stem cells and soft biomimetic hydrogels, which are specifically formulated with extracellular matrix analogs and tethered growth factors to provide selected biochemical cues for the guided differentiation towards chondrogenesis and osteogenesis. We demonstrate the ability to utilize these structures to (a) infill a focal chondral defect and mitigate macroscopic and cellular level changes in the cartilage surrounding the defect, and (b) support the development of a stratified multi-tissue scaffold for osteochondral tissue engineering., (© 2021 IOP Publishing Ltd.)

This article tells the story of how a public charter school serving students with autism spectrum disorder (ASD) adopted Direct Instruction (DI) as their primary form of instruction. The journey from recognizing the need for evidence-based curriculum focused on academic skills to integrating DI on a daily basis was outlined using a common implementation framework. We measured results of the implementation process on student outcomes using reading scores obtained from the Kaufman Test of Educational Achievement (KTEA-II Brief). Results for 67 students who participated in a DI reading program for at least 2 years suggest that the implementation of DI led to significantly improved reading scores; with some students demonstrating greatly accelerated rates of learning for their age. Our study suggests that the road to adoption of DI may be long, but the results are powerful for the individuals served. We offer our steps to implementation as a guide and resource to educators and behavior analysts eager to utilize DI in their settings., Competing Interests: Conflicts of InterestNo funding was received to assist with the preparation of this manuscript. The authors have no relevant financial or nonfinancial interests to disclose., (© Association for Behavior Analysis International 2021.)

Background: Previous vascularized composite allograft (VCA) studies from our laboratory have shown that topical FK506 delivery in non-human primates (NHPs) was limited by inadequate dermal penetration and rejection persisted. Herein, we report the first utilization of FK506 via subcutaneously implanted discs to mitigate VCA rejection in NHPs., Methods: Full major histocompatibility complex (MHC)-mismatched NHP pairs underwent partial-face VCA and FK506 disc implantation along the suture line. All allotransplants were maintained post-operatively for two months on the FK506 discs, methylprednisolone, mycophenolate mofetil, and supplemented with intramuscular FK506 if necessary. Group 1 (n=4) was used for optimization of the implant, while Group 2 (n=3) underwent delayed bone marrow transplantation (DBMT) after two months. VCA skin biopsies and peripheral blood samples were obtained for serial assessment of rejection and mixed chimerism by histopathology and flow cytometry respectively., Results: In Group 1, two technical failures occurred. Of the remaining two NHPs, one developed supratherapeutic levels of FK506 (50-120 ng/mL) and had to be euthanized on postoperative day (POD) 12. Reformulation of the implant resulted in stable FK506 levels (20-30 ng/mL) up to POD12 when further intramuscular (IM) FK506 injections were necessitated. In Group 2, two NHPs survived to undergo conditioning and one successfully developed chimerism at 2-3 weeks post-DBMT (96-97% granulocytes and 7-11% lymphocytes of recipient-origin). However, all three NHPs had to be terminated from study at POD64, 77 and 86 due to underlying post-transplant lymphoproliferative disorder. All VCAs remained rejection-free up to study endpoint otherwise., Conclusions: This study shows preliminary results of local FK506 implants in potentially mitigating VCA acute rejection for tolerance protocols based on mixed chimerism approach., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-21-313). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Vascularized composite allotransplantations (VCA) represent the most advanced reconstruction option for patients without autologous surgical possibilities after a complex tissue defect. Face and hand transplantations have changed disfigured patients' lives, giving them a new aesthetic and functional social organ. Despite promising outcomes, VCA is still underperformed due to life-long immunosuppression comorbidities and infectious complications. The rat is an ideal animal model for in vivo studies investigating immunological pathways and graft rejection mechanisms. Rats are also widely used in novel composite tissue graft preservation techniques, including perfusion and cryopreservation studies. Models used for VCA in rats must be reproducible, reliable, and efficient with low postoperative morbidity and mortality. Heterotopic limb transplantation procedures fulfill these criteria and are easier to perform than orthotopic limb transplants. Mastering rodent microsurgical models requires solid experience in microsurgery and animal care. Herein is reported a reliable and reproducible model of partial heterotopic osteomyocutaneous flap transplantation in rats, the postoperative outcomes, and the means of prevention of potential complications.

Objective: Transplantation of the hand or face, known as vascularized composite allotransplantation (VCA), has revolutionized reconstructive surgery. Notwithstanding, there are still several areas of improvement to mitigate immune rejection while sparing systemic adverse effects. The goal of this study was to evaluate the engraftment and viability of a genetically modified cell population pre-engrafted into a VCA transplant, to potentially act as a local biosensor to report and modify the graft in vivo. A rat fibroblast cell line genetically modified to secrete Gaussia-Luciferase (gLuc), which served as a constitutive biomarker of cells, was incorporated into a VCA to study the viability of biosensor cells in a syngeneic rat heterotopic partial hindlimb transplantation model., Results: Five perfusions were first performed as engineering runs to have a stable limb perfusion protocol, followed by 3 perfusions to analyze the cell engraftment during machine perfusion, and finally 4 perfusions to study in vivo persistence of the cell biosensors. Blood samples were collected to monitor gLuc secretion during perfusion and postoperatively. A time-dependent increase in gLuc secretion in the limb perfusion outflow during machine perfusion indirectly verified the presence of biosensors within the graft. After the ex vivo perfusion, VCA hindlimbs were analyzed for near infrared fluorescence emission that showed a presence of dyed engineered cells in all areas of the limbs. Postoperatively, gLuc was detectable 4 to 5 days after transplantation (W = 16, P = .02857). This study demonstrated that engineered cells could be successfully preimplanted into VCAs-an important step toward development of an in vivo biosensor platform to use in modulating acute VCA outcomes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Research has shown that training diagonal targets in a matrix may result in correct responses to the nondiagonal targets within the same matrix and novel targets from a separate matrix. This study replicated prior research using matrix training to teach tact noun-verb combinations to 3 male participants with autism who use a speech generating device to communicate. Two matrices were constructed (Matrix 1 and Generalization Matrix), using mastered nouns and verbs. Following baseline, diagonal targets within Matrix 1 were trained. Posttests were conducted for the Generalization Matrix and Matrix 1. Two participants showed recombinative generalization within Matrix 1 and correct responding to all targets within the novel generalization matrix. For the 3rd participant, recombinative generalization was observed within Matrix 1. However, correct responding with the generalization matrix targets was only observed after training with 3 additional matrices. These results replicate and extend previous findings., (© 2021 Society for the Experimental Analysis of Behavior.)

Developed by Siegfried ("Zig") Engelmann and colleagues, direct instruction (DI) has been recognized as an effective and replicable teaching model for decades. Although rooted in many principles of learning that behavior analysts utilize in daily practice, DI is not a common a component of behavior analytic services for learners with autism spectrum disorder (ASD). This may be attributed to behavior analysts' unfamiliarity with research evaluating the efficacy of DI with learners with ASD. This article synthesizes findings across studies evaluating DI with learners with ASD. The review addresses the contributions of the studies to date and identifies additional areas of research that may lead to more learners with ASD benefitting from DI., (© Association for Behavior Analysis International 2021.)

Mechanobiological cues influence chondrocyte biosynthesis and are often used in tissue engineering applications to improve the repair of articular cartilage in load-bearing joints. In this work, the biophysical effects of an applied dynamic compression on chondrocytes encapsulated in viscoelastic hydrazone covalent adaptable networks (CANs) is explored. Here, hydrazone CANs exhibit viscoelastic loss tangents ranging from (9.03 ± 0.01) 10 -4 to (1.67 ± 0.09) 10 -3 based on the molar percentages of alkyl-hydrazone and benzyl-hydrazone crosslinks. Notably, viscoelastic alkyl-hydrazone crosslinks improve articular cartilage specific gene expression showing higher SOX9 expression in free swelling hydrogels and dynamic compression reduces hypertrophic chondrocyte markers (COL10A1, MMP13) in hydrazone CANs. Interestingly, dynamic compression also improves matrix biosynthesis in elastic benzyl-hydrazone controls but reduces biosynthesis in viscoelastic alkyl-hydrazone CANs. Additionally, intermediate levels of viscoelastic adaptability demonstrate the highest levels of matrix biosynthesis in hydrazone CANs, demonstrating on average 70 ± 4 µg of sulfated glycosaminoglycans per day and 31 ± 3 µg of collagen per day over one month in dynamic compression bioreactors. Collectively, the results herein demonstrate the role of matrix adaptability and viscoelasticity on chondrocytes in hydrazone CANs during dynamic compression, which may prove useful for tissue engineering applications in load-bearing joints., (© 2021 Wiley-VCH GmbH.)

Vascularized composite allografts (VCAs) can restore fully functional anatomic units in patients with limb amputations or severe facial tissue loss. However, acute rejection of the skin is frequently observed and underscores the importance of developing tolerance induction protocols. In this study, we have characterized the skin immune system in VCAs. We demonstrate infiltration of recipient leukocytes, regardless of rejection status, and in tolerant mixed hematopoietic chimeras, the co-existence of these cells with donor leukocytes in the absence of rejection. Here we characterize the dermal T cell and epidermal Langerhans cell components of the skin immune system in our porcine model of VCA tolerance, and the kinetics of cutaneous chimerism in both of these populations in VCAs transplanted to tolerant and nontolerant recipients, as well as in host skin. Furthermore, in biopsies from the first patient to receive a hand transplant in our program, we demonstrate the presence of recipient T cells in the skin of the transplanted limb in the absence of clinical or histological evidence of rejection., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

To date there are no evidence-based comprehensive interventions for use in school settings. There are numerous barriers to delivery of high-quality interventions in schools that have limited the transfer of research-based interventions to school settings. Modular Approach to Autism Programing for Schools (MAAPS) is a framework for implementation of evidence-based interventions in school settings that is designed to address these barriers. The development and initial evaluation of MAAPS was conducted using an implementation-science framework and results indicate that MAAPS is aligned with needs and resources available in schools, that it had excellent social validity, and that there is good evidence that MAAPS is effective for addressing core and associated features of autism in educational settings.

Transplantation of vascularized composite allografts (VCAs) provides a means of restoring complex anatomical and functional units following burns and other disfigurement otherwise not amenable to conventional autologous reconstructive surgery. While short- to intermediate-term VCA survival is largely dependent on patient compliance with medication, the myriad of side effects resulting from lifelong systemic immunosuppression continue to pose a significant challenge. Topical immunosuppression is therefore a logical and attractive alternative for VCA. Current formulations are limited though, by poor skin penetration but this may be mitigated by conjugation of immunosuppressive drugs to TyroSpheres for enhanced delivery. Therefore, we investigated the topical application of FK506-TyroSpheres (in the form of a gel dressing) in a clinically relevant nonhuman primate VCA model to determine if allograft survival could be prolonged at reduced levels of maintenance systemic immunosuppression. Six Major Histocompatibility Complex (MHC)-mismatched cynomolgus macaques (Macaca fascicularis) served as reciprocal donors and recipients of radial forearm fasciocutaneous flaps. Standard Bacitracin ointment and FK506-TyroSpheres were applied every other day to the VCAs of animals in groups 1 (controls, n = 2) and 2 (experimental, n = 4), respectively, before gradual taper of systemic FK506. Clinical features of VCA rejection still developed when systemic FK506 fell below 10 ng/ml despite application of FK506-TyroSpheres and prolonged VCA survival was not achieved. However, unwanted systemic FK506 absorption was avoided with TyroSphere technology. Further refinement to optimize local drug delivery profiles to achieve and maintain therapeutic delivery of FK506 with TyroSpheres is underway, leveraging significant experience in controlled drug delivery to mitigate acute rejection of VCAs., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The autologous vein remains the standard conduit for lower extremity and coronary artery bypass grafting despite a 30%-50% 5-y failure rate, primarily attributable to intimal hyperplasia (IH) that develops in the midterm period (3-24 mo) of graft maturation. Our group discovered that externally strengthening vein grafts by cross-linking the adventitial collagen with photochemical tissue passivation (PTP) mitigates IH in an arteriovenous model at 4 wk. We now investigate whether this effect is retained in the midterm period follow-up., Methods: Six Hanford miniature pigs received bilateral carotid artery interposition vein grafts. In each animal, the external surface of one graft was treated with PTP before grafting, whereas the opposite side served as the untreated control. The grafts were harvested after 3 mo. Ultrasound evaluation of all vein grafts was performed at the time of grafting and harvest. The grafts were also evaluated histomorphometrically and immunohistologically for markers of IH., Results: All vein grafts were patent at 3 mo except one graft in the PTP-treated group because of early technical failure. The control vein grafts had significantly greater IH than PTP-treated grafts at 3 mo, as evidenced by the intimal area (2.6 ± 1.0 mm 2 versus 1.4 ± 1.5 mm 2 , respectively, P = 0.045) and medial area (5.1 ± 1.9 mm 2 versus 2.7 ± 2.4 mm 2 , respectively, P = 0.048). The control grafts had an increased presence and proliferation of mural myofibroblasts with greater smooth muscle actin and proliferating cell nuclear antigen staining., Conclusions: PTP treatment to the external surface of the vein grafts decreases IH at 3 mo after arteriovenous grafting and may prevent future graft failure., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Chondrocyte deformation influences disease progression and tissue regeneration in load-bearing joints. In this work, we found that viscoelasticity of dynamic covalent crosslinks temporally modulates the biophysical transmission of physiologically relevant compressive strains to encapsulated chondrocytes. Chondrocytes in viscoelastic alky-hydrazone hydrogels demonstrated (91.4 ± 4.5%) recovery of native rounded morphologies during mechanical deformation, whereas primarily elastic benzyl-hydrazone hydrogels significantly limited morphological recovery (21.2 ± 1.4%).

Applied behavior analysis has the most empirical support as intervention for pediatric feeding disorders, when a child does not eat or drink a sufficient quantity or variety of food to maintain proper nutrition. Interdisciplinary collaboration is crucial for diagnosis, referral, and management of pediatric feeding disorders because the etiology is complex and multifactorial. Thus, our aim is to provide information about how to recognize a feeding disorder, to delineate the environmental variables implicated in the etiology and maintenance of feeding disorders, and to provide recommendations for prevention and intervention for feeding disorders based on the applied-behavior analytic literature., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Skinner's (1957) classification of mand responses has spawned decades of research related to teaching individuals with developmental disabilities. However, few studies have evaluated how to teach individuals with autism to progress from simple to more complex mands for desired items and activities. The present study used a treatment package consisting of errorless teaching, differential reinforcement, and systematic decision rules to increase the number of words per mand utterance used by 6 children with autism. Daily probes were conducted in the absence of prompting and differential reinforcement throughout every stage of the treatment. Results showed that all children showed significant developmental gains in the mean length of utterances. Increased rates of manding, increased emission of mand frames, and decreased instances of indicating responses (i.e., pointing, reaching) in the absence of mands were also observed. Implications regarding the feasibility of intensive mand training in practice are discussed., Competing Interests: Conflict of InterestThe authors have no declared financial conflicts of interest., (© Association for Behavior Analysis International 2020.)

We examined whether different profiles of quality of life (QoL) existed among youth referred to an autism spectrum disorder (ASD) specialty clinic and, if present, determined if these groups were associated with different characteristics. Data were from parental report of 5-17 year-old youth (N = 476) who were scheduled to receive an evaluation at an ASD clinic. Parents completed questionnaires, including the Pediatric Quality of Life Inventory, assessing child and family functioning; providers reported diagnostic impressions. A latent profile analysis found five distinct groups: Low Risk, School Problems, Only Social Emotional Problems, and two Physical/Social Emotional Problems. The groups differed on clinical characteristics and family functioning. These findings have implications for more efficient and effective evaluations in service delivery systems serving complex patients.

Background: Transplantation of vascularized composite allografts is limited mainly by the need for life-long immunosuppression. The consequent side effects and looming specter of chronic rejection portend eventual allograft loss. Development of tolerogenic protocols is thus of utmost importance to the field of vascularized composite allograft transplantation., Methods: With a modified delayed tolerance induction protocol, 10 cynomolgus macaques received hand (n = 2) or face vascularized composite allografts across both full and haploidentical major histocompatibility complex barriers before donor bone marrow transplantation at a later date. Protocol and for-cause allograft skin biopsies were performed for immunohistochemical analysis and analysis of donor-recipient leukocyte contribution; mixed chimerism in peripheral blood and in vitro immune responses were assessed serially., Results: Before bone marrow transplantation, maintenance immunosuppression for 4 months led to lethal complications, including posttransplant lymphoproliferative disorder (in two of four recipients), which necessitated early study termination. Shortening the maintenance period to 2 months was clinically relevant and allowed all subsequent subjects (n = 6) to complete the delayed tolerance induction protocol. Acute rejection developed within the first 2 to 4 weeks after transplantation, with corresponding near-complete turnover of allograft leukocytes from donor to recipient origin, but donor-specific antibodies remained negative. After bone marrow transplantation, mixed chimerism failed to develop, although carboxyfluorescein succinimidyl ester mixed lymphocyte reaction demonstrated generalized unresponsiveness. However, the accrual of subsequent rejection episodes eventually culminated in graft vasculopathy and irreversible allograft loss., Conclusions: Despite the various advantages of the delayed tolerance induction protocol, it failed to reliably induce mixed chimerism and thus immunologic tolerance to vascularized composite allografts, given currently available immunosuppression treatment options. Ongoing work shows promise in overcoming these limitations.

Responding by individuals in groups has been a prominent interest of the field of psychology. Experimental analyses of human behavior have provided some unique findings of the role that the environment, including both social and nonsocial stimuli, may have on individual responding. Cooperative and competitive contingencies, previously evaluated in animal and human operant research, provide unique insight into applied interventions, in particular group contingencies. The current manuscript attempts to bridge these two literatures to foster the development of more effective technologies and lines of experimental or translational research that may better inform interventions in the applied realm., (© Association for Behavior Analysis International 2020.)

Direct instruction (DI) is an evidence-based approach to education that has been shown to be effective across a wide variety of student populations. Growing evidence suggests that DI may be an efficacious strategy for individuals with autism spectrum disorder (ASD). The current study aimed to evaluate the feasibility of using DI with students with ASD who utilize speech-generating devices (SGDs); 3 students with ASD whose primary mode of communication was an SGD were exposed to the Language for Learning Curriculum, Lessons 1-10. Student performance on pre- and posttests was measured, as well as student performance on exercises within each lesson. The average time to complete an exercise, number of repetitions, number of terminated sessions, and student affect were also evaluated. Results indicated that all 3 students could participate and complete exercises with some modifications to support SGD use. The students demonstrated improved performance, positive affect, and overall timely completion of exercises. Taken together, these findings suggest that DI may be feasible for some students with ASD who utilize SGDs., Competing Interests: Conflict of InterestThe authors have no declared financial conflicts of interest., (© Association for Behavior Analysis International 2020.)

Background and Objectives: Wound contracture formation from excessive myofibroblast activity can result in debilitating morbidities. There are currently no treatments to prevent contracture. Photochemical tissue passivation (PTP), an established, safe, and user-friendly treatment modality, crosslinks collagen by a light-activated process, thus modulating the wound healing response and scarring. We hypothesised that PTP treatment would reinforce wounds by blunting the fibrotic response thus limiting contracture., Study Design/materials and Methods: Full-thickness, 1 cm × 1 cm excisional wounds were created on the dorsum of 32 C57BL/6 mice. Treated wounds were painted with photosensitizing dye and exposed to visible light. Wounds were serially photographed over 6 weeks to measure wound contracture. At 7, 14, 21, and 42 days after wound creation, mice were euthanized and wounds were harvested for histologic review by a dermatopathologist., Results: By Day 7, control wounds had significantly more contracture than those treated with PTP (33.0 ± 17.1% and 19.3 ± 9.0%, respectively; P = 0.011). PTP-treated wounds maintained approximately 20% less contracture than controls from Day 14 and on (P < 0.05). By Day 42, wounds had contracted by 86.9 ± 5.5% in controls and 64.2 ± 3.2% in PTP-treated wounds (P < 0.03). Histologically, PTP wounds had earlier growth and development of dermal collagen, neovascularization, and development of skin appendages, compared with control wounds., Conclusions: PTP significantly limits contracture of full-thickness wounds and improves wound healing. PTP-treated wounds histologically demonstrate more mature structural organization than untreated wounds and closely resemble native skin. PTP treatment may be applicable not only for excisional wounds, but also for wounds with a high incidence of contracture and associated morbidity. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc., (© 2019 Wiley Periodicals, Inc.)

In this editorial, we provide commentary on the state of diversity and equity in the practice of behavior analysis. We describe themes from this special issue and call upon members of the field of applied behavior analysis to live a values-driven life that involves the systematic and data-driven practice of diversity and equity each and every day., Competing Interests: Conflict of InterestThe authors declare that they have no conflicts of interest., (© Association for Behavior Analysis International 2019.)

Mechanisms of chronic rejection of vascularized composite allografts (VCA) remain poorly understood and likely present along a spectrum of highly varied clinicopathological findings. Across both animal and human VCA however, graft vasculopathy (GV) has been the most consistent pathological finding resulting clinically in irreversible allograft dysfunction and eventual loss. A literature review of all reported clinical VCA cases with documented GV up to December 2018 was thus performed to elucidate the possible mechanisms involved. Relevant data extracted include C4d deposition, donor-specific antibody (DSA) formation, extent of human leukocyte antigen (HLA) mismatch, pretransplant panel reactive antibody levels, induction and maintenance immunosuppression used, the number of preceding acute rejection episodes, and time to histological confirmation of GV. Approximately 6% (13 of 205) of all VCA patients reported to date developed GV at a mean of 6 years post-transplantation. 46% of these patients have either lost or had their VCAs removed. Neither C4d nor DSA alone was predictive of GV development; however, when both are present, VCA loss appears inevitable due to progressive GV. Of utmost concern, GV in VCA does not appear to be abrogated by currently available immunosuppressive treatment and is essentially irreversible by the time of diagnosis with allograft loss a likely eventuality., (© 2019 Steunstichting ESOT.)

While matrix-assisted autologous chondrocyte implantation has emerged as a promising therapy to treat focal chondral defects, matrices that support regeneration of hyaline cartilage remain challenging. The goal of this work was to investigate the potential of a matrix metalloproteinase (MMP)-sensitive poly(ethylene glycol) (PEG) hydrogel containing the tethered growth factor, transforming growth factor β3 (TGF-β3), and compare cartilage regeneration in vitro and in vivo. The in vitro environment comprised chemically-defined medium while the in vivo environment utilized the subcutaneous implant model in athymic mice. Porcine chondrocytes were isolated and expanded in 2D culture for 10 days prior to encapsulation. The presence of tethered TGF-β3 reduced cell spreading. Chondrocyte-laden hydrogels were analyzed for total sulfated glycosaminoglycan and collagen contents, MMP activity, and spatial deposition of aggrecan, decorin, biglycan, and collagens type II and I. The total amount of extracellular matrix (ECM) deposited in the hydrogel constructs was similar in vitro and in vivo. However, the in vitro environment was not able to support long-term culture up to 64 days of the engineered cartilage leading to the eventual breakdown of aggrecan. The in vivo environment, on the other hand, led to more elaborate ECM, which correlated with higher MMP activity, and an overall higher quality of engineered tissue that was rich in aggrecan, decorin, biglycan and collagen type II with minimal collagen type I. Overall, the MMP-sensitive PEG hydrogel containing tethered TGF-β3 is a promising matrix for hyaline cartilage regeneration in vivo. STATEMENT OF SIGNIFICANCE: Regenerating hyaline cartilage remains a significant clinical challenge. The resultant repair tissue is often fibrocartilage, which long-term cannot be sustained. The goal of this study was to investigate the potential of a synthetic hydrogel matrix containing peptide crosslinks that can be degraded by enzymes secreted by encapsulated cartilage cells (i.e., chondrocytes) and tethered growth factors, specifically TGF-β3, to provide localized chondrogenic cues to the cells. This hydrogel led to hyaline cartilage-like tissue growth in vitro and in vivo, with minimal formation of fibrocartilage. However, the tissue formed in vitro, could not be maintained long-term. In vivo this hydrogel shows great promise as a potential matrix for use in regenerating hyaline cartilage., (Copyright © 2019. Published by Elsevier Ltd.)