CAR-T cells and CAR-Tregs targeting conventional type-1 dendritic cell suppress experimental autoimmune encephalomyelitis.

Conventional type 1 dendritic cells (DC1) contribute to the development of pathogenic T helper type 1 (Th1) cells in part the production of the proinflammatory cytokine interleukin-12. Thus, depletion of DC1 has the potential to dampen autoimmune responses. Here, we developed X-C motif chemokine receptor 1 (XCR1)-specific chimeric antigen receptor (CAR)-T cells and CAR-Tregs that specifically targeted DC1.

Biomechanical Assessment of Bicortical Suspension Device Fixation for Proximal Tibiofibular Joint Instability: Single Versus Double Device.

Background: Bicortical suspension device (BCSD) fixation treats proximal tibiofibular joint (PTFJ) instability in both the anterolateral and posteromedial directions. However, biomechanical data are lacking as to whether this technique restores the native stability and strength of the joint.

Purpose: To test (1) if BCSD fixation restores the native stability and strength and (2) if using 2 devices is needed.

Using decoys and camera traps to estimate depredation rates and neonate survival.

Ungulate neonates-individuals less than four weeks old-typically experience the greatest predation rates, and variation in their survival can influence ungulate population dynamics. Typical methods to measure neonate survival involve capture and radio-tracking of adults and neonates to discover mortality events. This type of fieldwork is invasive and expensive, can bias results if it leads to neonate abandonment, and may still have high uncertainty about the predator species involved.

Regulatory ligand binding in plant chalcone isomerase-like (CHIL) proteins.

Chalcone isomerase-like (CHIL) protein is a noncatalytic protein that enhances flavonoid content in green plants by serving as a metabolite binder and a rectifier of chalcone synthase (CHS). Rectification of CHS catalysis occurs through direct protein-protein interactions between CHIL and CHS, which alter CHS kinetics and product profiles, favoring naringenin chalcone (NC) production. These discoveries raise questions about how CHIL proteins interact structurally with metabolites and how CHIL-ligand interactions affect interactions with CHS.

Editorial Commentary: External Fixation and/or Vascular Injury Is Associated With Postoperative Arthrofibrosis After Multiple-Ligament Knee Injury Reconstruction.

Patients with a body mass index over 30 do not have a significant increase in postoperative arthrofibrosis after multiple-ligament knee injury (MLKI) reconstruction compared with patients with a body mass index under 30. However, although this may be associated with the severity of injury, recent research has shown that patients who undergo external fixation at index surgery and/or who have vascular injury are at increased risk of requiring manipulation under anesthesia. This finding is clinically significant in that it is reassuring that stiffness requiring manipulation is no more likely to develop in obese patients than in non-obese patients after MLKI reconstruction.

Rationale for integration of services for diabetes mellitus and diabetic retinopathy in Kenya.

Background: Good diabetes mellitus (diabetes) and diabetic retinopathy (DR) management depends on the strength of the health system, prompting us to conduct a health system assessment for diabetes and DR in Kenya. We used diabetes and DR as tracer conditions to assess the strengths and weaknesses in the health system, and potential interventions to strengthen the health system. In this paper, we report on the need and relevance of integration to strengthen diabetes and DR care.

Superiorly and transversely orienting the bicortical suspension device provides optimal anterolateral stability to the proximal tibiofibular joint: a finite-element study.

Purpose: Instability of the proximal tibiofibular joint (PTFJ) can be treated with bicortical suspension (BCS) fixation. However, the ideal location, orientation, and configuration to apply one or two BCS devices are not clear.

Methods: A finite-element model of the PTFJ was created from a female adult's CT dataset.

Adjustable-loop cortical suspension device for posterolateral corner reconstruction in the setting of fibular avulsion fracture: a case series and novel technique description.

Introduction: A novel technique using an adjustable-loop cortical suspension toggle device for reduction of a fibular head avulsion fracture (arcuate fracture) in posterolateral corner (PLC) reconstruction is described. Results of clinical follow-up are presented.

Materials And Methods: 9 patients were retrospectively identified who underwent posterolateral corner reconstruction using an adjustable-loop cortical suspension toggle device.

Isolated Osteochondral Autograft Versus Allograft Transplantation for the Treatment of Symptomatic Cartilage Lesions of the Knee: A Systematic Review and Meta-analysis.

Background: Focal cartilage lesions of the knee remain a difficult entity to treat. Current treatment options include arthroscopic debridement, microfracture, autograft or allograft osteochondral transplantation, and cell-based therapies such as autologous chondrocyte transplantation. Osteochondral transplantation techniques restore the normal topography of the condyles and provide mature hyaline cartilage in a single-stage procedure.

Comparable Subjective and Objective Clinical Outcomes After Fibular or Combined Tibial-Fibular-based Reconstruction of the Posterolateral Corner of the Knee: A Systematic Review and Meta-analysis.

Introduction: To compare subjective and objective outcomes of fibular and combined tibial-fibular (TF)-based posterolateral corner (PLC) reconstruction.

Methods: A systematic review of literature reporting outcomes of posterolateral corner reconstruction was conducted including outcome studies of surgically treated PLC injuries with a minimum 1-year follow-up, postoperative subjective and objective outcomes including the patient-reported outcome scorings of Lysholm score, International Knee Documentation Committee evaluation (subjective and objective), dial test, and varus stress radiographs.

Results: The 32 studies included comprised 40 cohorts: 12 cohorts (n = 350 knees) used a fibular-based technique, and 28 cohorts (n = 593 knees) used a combined TF-based technique.

Current Trends in Orthobiologics: An 11-Year Review of the Orthopaedic Literature.

Background: The use of "orthobiologics" or regenerative therapies in orthopaedic surgery has grown in recent years. Particular interest has been raised with regard to platelet-rich plasma, bone marrow aspirate, adipose-derived cells, and amniotic cells. Although studies have analyzed outcomes after orthobiologic treatment, no study has analyzed how the literature as a whole has evolved.

Intraoperative and Early (90-Day) Postoperative Complications and Associated Variables with Multiligamentous Knee Reconstruction: 15-year Experience from a Single Academic Institution.

Purpose: We sought to determine the rate of intraoperative and early postoperative (90-day) complications of multiligamentous knee reconstruction surgeries, both medical and surgical, and associated variables from the 15-year experience of a single academic institution.

Methods: Patients treated at a single academic institution between 2005 and 2019 who underwent multiligament knee surgery were identified. Inclusion criteria included intervention with 2+ ligament reconstructions performed concurrently, and more than 90 days postoperative follow-up.

Emerging Therapeutics for Immune Tolerance: Tolerogenic Vaccines, T cell Therapy, and IL-2 Therapy.

Autoimmune diseases affect roughly 5-10% of the total population, with women affected more than men. The standard treatment for autoimmune or autoinflammatory diseases had long been immunosuppressive agents until the advent of immunomodulatory biologic drugs, which aimed at blocking inflammatory mediators, including proinflammatory cytokines. At the frontier of these biologic drugs are TNF-α blockers.

Low-Zone IL-2 Signaling: Fusion Proteins Containing Linked CD25 and IL-2 Domains Sustain Tolerogenic Vaccination and Promote Dominance of FOXP3 Tregs .

Low-zone IL-2 signaling is key to understanding how CD4 CD25 FOXP3 regulatory T cells (Tregs) exhibit dominance and overgrow conventional effector T cells (Tcons) that typically express lower levels of the IL-2 receptor alpha chain (i.e., CD25).

An update on graft-tunnel mismatch in anterior cruciate ligament reconstruction: A survey of the experts in the field of orthopedic sports medicine demonstrates no clear consensus in management.

Background: The purpose of this study was to identify and report on the rate at which leaders in orthopaedic surgery are encountering GTM, their treatment methods and to identify whether these clinicians' demographics or techniques correlate with their GTM incidence and/or treatment algorithms.

Methods: A survey was sent to identify the rate at which member orthopaedic surgeons of the American Orthopaedic Society for Sports Medicine (AOSSM), the National Football League Physicians Society (NFLPS), and the Herodicus Society are encountering GTM in ACL reconstruction with BTB graft and to establish what methods are most commonly utilized.

Results: In total, 260 orthopaedic surgeons completed the survey.

Atlantic Coast Conference Mandatory College Football Medical Observer. A Necessary Addition to the Preexisting Medical Team?

Background: Some NCAA conferences now require a press box-based Medical Observer for all football games to identify injuries missed by on-field providers. The objective of this study was to determine whether a Medical Observer identified injuries missed by the on-field medical personnel.

Methods: This was a comparative observational study of injury identification methods which was done at nine NCAA football games.

Tolerogenic vaccines: Targeting the antigenic and cytokine niches of FOXP3 regulatory T cells.

FOXP3 regulatory T cells (Tregs) constitute a critical barrier that enforces tolerance to both the self-peptidome and the extended-self peptidome to ensure tissue-specific resistance to autoimmune, allergic, and other inflammatory disorders. Here, we review intuitive models regarding how T cell antigen receptor (TCR) specificity and antigen recognition efficiency shape the Treg and conventional T cell (Tcon) repertoires to adaptively regulate T cell maintenance, tissue-residency, phenotypic stability, and immune function in peripheral tissues. Three zones of TCR recognition efficiency are considered, including Tcon recognition of specific low-efficiency self MHC-ligands, Treg recognition of intermediate-efficiency agonistic self MHC-ligands, and Tcon recognition of cross-reactive high-efficiency agonistic foreign MHC-ligands.

Feasibility of a cluster randomized controlled trial on the effectiveness of peer-led health education interventions to increase uptake of retinal examination for diabetic retinopathy in Kirinyaga, Kenya: a pilot trial.

Background: People living with diabetes can reduce their risk of vision loss from diabetic retinopathy by attending screening, which enables early detection and timely treatment. The aim of this pilot trial was to assess the feasibility of a full-scale cluster randomized controlled trial of an intervention to increase uptake of retinal examination in this population, as delivered within existing community-based diabetes support groups (DSGs).

Methods: All 16 DSGs in Kirinyaga county were invited to participate in the study.

A GM-CSF-neuroantigen tolerogenic vaccine elicits inefficient antigen recognition events below the CD40L triggering threshold to expand CD4 CD25 FOXP3 Tregs that inhibit experimental autoimmune encephalomyelitis (EAE).

Background: Tolerogenic vaccines represent antigen-specific interventions designed to re-establish self-tolerance and thereby alleviate autoimmune diseases, which collectively comprise over 100 chronic inflammatory diseases afflicting more than 20 million Americans. Tolerogenic vaccines comprised of single-chain GM-CSF-neuroantigen (GMCSF-NAg) fusion proteins were shown in previous studies to prevent and reverse disease in multiple rodent models of experimental autoimmune encephalomyelitis (EAE) by a mechanism contingent upon the function of CD4 CD25 FOXP3 regulatory T cells (Tregs). GMCSF-NAg vaccines inhibited EAE in both quiescent and inflammatory environments in association with low-efficiency T cell receptor (TCR) signaling events that elicited clonal expansion of immunosuppressive Tregs.

Effects of body size on estimation of mammalian area requirements.

Accurately quantifying species' area requirements is a prerequisite for effective area-based conservation. This typically involves collecting tracking data on species of interest and then conducting home-range analyses. Problematically, autocorrelation in tracking data can result in space needs being severely underestimated.

Peer-support to increase uptake of screening for diabetic retinopathy: process evaluation of the DURE cluster randomized trial.

Background: There is limited evidence on how implementation of peer support interventions influences effectiveness, particularly for individuals with diabetes. We conducted a cluster randomized controlled trial to compare the effectiveness of a peer-led health education package versus usual care to increase uptake of screening for diabetic retinopathy (DR).

Methods: Our process evaluation used a mixed-method design to investigate the recruitment and retention, reach, dose, fidelity, acceptability, and context of implementation, and was guided by the Consolidated Framework for Implementation Research (CFIR).

Bird community shifts associated with saltwater exposure in coastal forests at the leading edge of rising sea level.

Rising sea levels dramatically alter the vegetation composition and structure of coastal ecosystems. However, the implications of these changes for coastal wildlife are poorly understood. We aimed to quantify responses of avian communities to forest change (i.