Differentiation of regulatory myeloid and T-cells from adult human hematopoietic stem cells after allogeneic stimulation.

Introduction: Donor hematopoietic stem cell (DHSC) infusions are increasingly being studied in transplant patients for tolerance induction.

Methods: To analyze the fate of infused DHSCs in patients, we developed an culture system utilizing CD34DHSCs stimulated with irradiated allogeneic cells in cytokine supplemented medium long-term.

Results: Flow cytometric analyses revealed loss of the CD34 marker and an increase in CD33 myeloid and CD3 T-cell proportion by 10.

Single-cell coating with biomimetic extracellular nanofiber matrices.

Cell therapies offer great promise in the treatment of diseases and tissue regeneration, but their clinical use has many challenges including survival, optimal performance in their intended function, or localization at sites where they are needed for effective outcomes. We report here on a method to coat a biodegradable matrix of biomimetic nanofibers on single cells that could have specific functions ranging from cell signaling to targeting and helping cells survive when used for therapies. The fibers are composed of peptide amphiphile (PA) molecules that self-assemble into supramolecular nanoscale filaments.

CD4CD25FOXP3 regulatory T cells: a potential "armor" to shield "transplanted allografts" in the war against ischemia reperfusion injury.

Despite the advances in therapeutic interventions, solid organ transplantation (SOT) remains the "gold standard" treatment for patients with end-stage organ failure. Recently, vascularized composite allotransplantation (VCA) has reemerged as a feasible treatment option for patients with complex composite tissue defects. In both SOT and VCA, ischemia reperfusion injury (IRI) is inevitable and is a predominant factor that can adversely affect transplant outcome by potentiating early graft dysfunction and/or graft rejection.

Evaluation of Immunocompetence and Biomarkers of Tolerance in Chimeric and Immunosuppression-free Kidney Allograft Recipients.

Background: Thirty-seven patients have received a living-donor kidney transplant in a phase 2 study designed to induce tolerance with facilitated allogeneic hematopoietic stem cell transplant. The study protocol is based on tolerogenic CD8 + /T-cell receptor - facilitating cells (FCR001; also including hematopoietic stem cells and αβ-T-cell receptor + T cells) and low-dose, nonmyeloablative conditioning. Persistent chimerism allowing full immunosuppression (IS) withdrawal was achieved in 26 patients (time off IS 36-123 mo).

Introduction of a homeless health outreach team in Northern New South Wales: is acute service usage reduced?

Objective: To examine if there is a relationship between introducing a Homeless Health Outreach Team (HHOT) and reduced acute Mental Health service usage.

Methods: Electronic Medical Record (EMR) data were collected on a group of clients of the Tweed Byron HHOT 6 months before and after establishing the service. The data were evaluated for demographics, and differences in Emergency Department (ED) presentations, mental health admissions, length of stay and community mental health engagement.

Foxp3+ regulatory T cell therapy for tolerance in autoimmunity and solid organ transplantation.

Regulatory T cells (Tregs) are critical for tolerance in humans. The exact mechanisms by which the loss of peripheral tolerance leads to the development of autoimmunity and the specific role Tregs play in allograft tolerance are not fully understood; however, this population of T cells presents a unique opportunity in the development of targeted therapeutics. In this review, we discuss the potential roles of Foxp3+ Tregs in the development of tolerance in transplantation and autoimmunity, and the available data regarding their use as a treatment modality.

Separability of Human Motor Memories during reaching adaptation with force cues.

Judging by the breadth of our motor repertoire during daily activities, it is clear that learning different tasks is a hallmark of the human motor system. However, for reaching adaptation to different force fields, the conditions under which this is possible in laboratory settings have remained a challenging question. Previous work has shown that independent movement representations or goals enabled dual adaptation.

Pre-transplant infusion of donor leukocytes treated with extracorporeal photochemotherapy induces immune hypo-responsiveness and long-term allograft survival in murine models.

Recipients of solid organ transplantation (SOT) rely on life-long immunosuppression (IS), which is associated with significant side effects. Extracorporeal photochemotherapy (ECP) is a safe, existing cellular therapy used to treat transplant rejection by modulating the recipient's own blood cells. We sought to induce donor-specific hypo-responsiveness of SOT recipients by infusing ECP-treated donor leukocytes prior to transplant.

Adaptive Feedback Control in Human Reaching Adaptation to Force Fields.

Sensorimotor adaptation is a central function of the nervous system, as it allows humans and other animals to flexibly anticipate their interaction with the environment. In the context of human reaching adaptation to force fields, studies have traditionally separated feedforward (FF) and feedback (FB) processes involved in the improvement of behavior. Here, we review computational models of FF adaptation to force fields and discuss them in light of recent evidence highlighting a clear involvement of feedback control.

Composition and decomposition of visuomotor maps during manual tracking.

Adapting hand movements to changes in our body or the environment is essential for skilled motor behavior, as is the ability to flexibly combine experience gathered in separate contexts. However, it has been shown that when adapting hand movements to two different visuomotor perturbations in succession, interference effects can occur. Here, we investigate whether these interference effects compromise our ability to adapt to the superposition of the two perturbations.

Savings in Human Force Field Learning Supported by Feedback Adaptation.

Savings have been described as the ability of healthy humans to relearn a previously acquired motor skill faster than the first time, which in the context of motor adaptation suggests that the learning rate in the brain could be adjusted when a perturbation is recognized. Alternatively, it has been argued that apparent savings were the consequence of a distinct process that instead of reflecting a change in the learning rate, revealed an explicit re-aiming strategy. Based on recent evidence that feedback adaptation may be central to both planning and control, we hypothesized that this component could genuinely accelerate relearning in human adaptation to force fields (FFs) during reaching.

Tackling Chronic Kidney Transplant Rejection: Challenges and Promises.

Despite advances in post-transplant management, the long-term survival rate of kidney grafts and patients has not improved as approximately forty percent of transplants fails within ten years after transplantation. Both immunologic and non-immunologic factors contribute to late allograft loss. Chronic kidney transplant rejection (CKTR) is often clinically silent yet progressive allogeneic immune process that leads to cumulative graft injury, deterioration of graft function.

More precise tracking of horizontal than vertical target motion with both the eyes and hand.

When tracking targets moving in various directions with one's eyes, horizontal components of pursuit are more precise than vertical ones. Is this because horizontal target motion is predicted better or because horizontal movements of the eyes are controlled more precisely? When tracking a visual target with the hand, the eyes also track the target. We investigated whether the directional asymmetries that have been found during isolated eye movements are also present during such manual tracking, and if so, whether individual participants' asymmetry in eye movements is accompanied by a similar asymmetry in hand movements.

Immune and gene expression profiling during tacrolimus to everolimus conversion early after liver transplantation.

Early elimination of tacrolimus in favor of everolimus can improve renal function in liver transplant recipients. However, as this approach increases the risk of acute rejection, it may benefit from predictive biomarkers guiding weaning. We enrolled 20 recipients on stable tacrolimus + everolimus to undergo tacrolimus withdrawal early post-liver transplant.

Chimerism and tolerance: past, present and future strategies to prolong renal allograft survival.

Purpose Of Review: Immunological factors are a major cause of kidney allograft loss. Calcineurin inhibitors (CNIs) have improved short-term kidney allograft survival; however, they in turn contribute to long-term kidney allograft loss from chronic CNI nephrotoxicity. Tolerance induction in transplantation can avoid the long-term adverse effects of immunosuppressive medications.

Rapid Changes in Movement Representations during Human Reaching Could Be Preserved in Memory for at Least 850 ms.

Humans adapt to mechanical perturbations such as forcefields (FFs) during reaching within tens of trials. However, recent findings suggested that this adaptation may start within one single trial, i.e.

Taking the Next Step: a Neural Coaptation Orthotopic Hind Limb Transplant Model to Maximize Functional Recovery in Rat.

Limb transplant in particular and vascularized composite allotransplant (VCA) in general have wide therapeutic promise that have been stymied by current limitations in immunosuppression and functional neuromotor recovery. Many animal models have been developed for studying unique features of VCA, but here we present a robust reproducible model of orthotopic hind limb transplant in rats designed to simultaneously investigate both aspects of current VCA limitation: immunosuppression strategies and functional neuromotor recovery. At the core of the model rests a commitment to meticulous, time-tested microsurgical techniques such as hand sewn vascular anastomoses and hand sewn neural coaptation of the femoral nerve and the sciatic nerve.

Sex differences in visuomotor tracking.

There is a growing interest in sex differences in human and animal cognition. However, empirical evidences supporting behavioral and neural sex differences in humans remain sparse. Visuomotor behaviors offer a robust and naturalistic empirical framework to seek for the computational mechanisms underlying sex biases in cognition.

Feedback Adaptation to Unpredictable Force Fields in 250 ms.

Motor learning and adaptation are important functions of the nervous system. Classical studies have characterized how humans adapt to changes in the environment during tasks such as reaching, and have documented improvements in behavior across movements. However, little is known about how quickly the nervous system adapts to such disturbances.

Transdiagnostic internet-delivered CBT and mindfulness-based treatment for depression and anxiety: A randomised controlled trial.

Aim: To examine the efficacy of transdiagnostic internet-delivered cognitive behavioural therapy (iCBT), mindfulness-enhanced iCBT, and stand-alone online mindfulness training compared with a usual care control group (TAU) for clinical anxiety and depression.

Method: Individuals ( = 158) with a DSM-5 diagnosis of a depressive and/or anxiety disorder were randomised to one of the three clinician-guided online interventions, or TAU over a 14-week intervention period. The primary outcomes were self-reported depression (PHQ-9) and anxiety (GAD-7) severity at post-treatment.

Gaze behavior during visuomotor tracking with complex hand-cursor dynamics.

The ability to track a moving target with the hand has been extensively studied, but few studies have characterized gaze behavior during this task. Here we investigate gaze behavior when participants learn a new mapping between hand and cursor motion, such that the cursor represented the position of a virtual mass attached to the grasped handle via a virtual spring. Depending on the experimental condition, haptic feedback consistent with mass-spring dynamics could also be provided.

Immunosuppression Withdrawal in Liver Transplant Recipients on Sirolimus.

Background And Aims: As conversion from calcineurin inhibitor to sirolimus (SRL), a mechanistic target of rapamycin inhibitor (mTOR-I), has been shown to enhance immunoregulatory profiles in liver transplant (LT) recipients (LTRs), mTOR-I therapy might allow for increased success of immunosuppression (IS) withdrawal. Our aim was to determine if operational tolerance could be observed in LTRs withdrawn from SRL and if blood/graft tolerance biomarkers were predictive of successful withdrawal.

Approach And Results: We performed a prospective trial of SRL monotherapy withdrawal in nonimmune, nonviremic LTRs > 3 years post-LT.