Autologous chondrocyte implantation for treatment of articular cartilage defects in the knee and ankle of football (soccer) players

Background: Autologous chondrocyte implantation (ACI) continues to evolve into one of the most efficient and common techniques for repair of articular cartilage defects. Significant progress has been made within the last decade regarding its application in the context of professional sports, such as football. This article provides a current overview of the application of ACI in the context of amateur and professional football. Methods: Clinical studies involving football players and other high-impact sports athletes treated with ACI were reviewed. The scientific and technical development of ACI was evaluated considering latest publications, and analyzed for treatment outcome parameters. Results: Football players reported good to excellent results after treatment with ACI or matrix-associated chondrocyte implantation (MACI). Activity scores and clinical knee and ankle scores were significantly improved after surgery. Great advances have been made in surgery specific rehabilitation algorithms, leading to shorter return to play times. New surgical techniques have been introduced, reducing the 2-stage design of ACI to only one surgical intervention, accelerating return to play time further while reducing morbidity. Conclusion: Surgical repair of focal articular cartilage defects via ACI in football players often provides successful return-to-competition and produces long lasting regeneration tissue, enabling players to continue their career on the pre-injury level of play. The technique itself is constantly evolving, addressing initial shortcomings and making it more widespread available to the recreational and professional athlete

A note on quasinormal modes: A tale of two treatments

There is an apparent discrepancy in the literature with regard to the quasinormal mode frequencies of Schwarzschild-de Sitter black holes in the degenerate-horizon limit. On the one hand, a Poschl-Teller-inspired method predicts that the real part of the frequencies will depend strongly on the orbital angular momentum of the perturbation field whereas, on the other hand, the degenerate limit of a monodromy-based calculation suggests there should be no such dependence (at least, for the highly damped modes). In the current paper, we provide a possible resolution by critically re-assessing the limiting procedure used in the monodromy analysis.Comment: 11 pages, Revtex format; (v2) new addendum in response to reader comments, also references, footnote and acknowledgments adde

Size of cartilage defects and the need for repair: a systematic review

Background: Cartilage defects are treated with a wide array of non-operative and surgical procedures. Optimal choice of treatment depends on lesion depth and size. Objectives: To review and summarize current data on the management of cartilage injuries in joints as it relates to defect size. Data sources: MEDLINE, Cochrane Central Register of Controlled Trials & Cochrane Library, CINHAL. Study eligibility criteria, participants, and interventions: Inclusion: (1) Studies investigating patients who underwent cartilage repair of the shoulder, elbow, hip, knee, and ankle. (2) Studies reporting outcome measures and treated lesion size. Exclusion: (1) No mention of defect size. (2) Joints not mentioned above. (3) 1.5 cm2 mostly addressed with cell-based therapies such as autologous cartilage implantation (ACI), or matrix associated cartilage implantation (MACI). Large lesions often are the domain of osteochondral autograft transfer system (OATS). Limitations: Prospective randomized controlled studies are not available for every joint and many studies represent case studies with limited implications for treatment decisions. Conclusions and implications of key findings: Evidence-based treatment selection based on cartilage defect size can be beneficial. Systematic review registration number: 276559

Common principles and best practices for engineering microbiomes

Despite broad scientific interest in harnessing the power of Earth's microbiomes, knowledge gaps hinder their efficient use for addressing urgent societal and environmental challenges. We argue hat structuring research and technology developments around a design-build-test-learn (DBTL) cycle will advance microbiome engineering and spur new discoveries on the basic scientific principles governing microbiome function. In this Review, we present key elements of an iterative DBTL cycle for microbiome engineering, focusing on generalizable approaches, including top-down and bottom-up design processes, synthetic and self-assembled construction methods, and emerging tools to analyze microbiome function. These approaches can be used to harness microbiomes for broad applications related to medicine, agriculture, energy, and the environment. We also discuss key challenges and opportunities of each approach and synthesize them into best practice guidelines for engineering microbiomes. We anticipate that adoption of a DBTL framework will rapidly advance microbiome-based biotechnologies aimed at improving human and animal health, agriculture, and enabling the bioeconomy

Noise Kernel and Stress Energy Bi-Tensor of Quantum Fields in Hot Flat Space and Gaussian Approximation in the Optical Schwarzschild Metric

Continuing our investigation of the regularization of the noise kernel in curved spacetimes [N. G. Phillips and B. L. Hu, Phys. Rev. D {\bf 63}, 104001 (2001)] we adopt the modified point separation scheme for the class of optical spacetimes using the Gaussian approximation for the Green functions a la Bekenstein-Parker-Page. In the first example we derive the regularized noise kernel for a thermal field in flat space. It is useful for black hole nucleation considerations. In the second example of an optical Schwarzschild spacetime we obtain a finite expression for the noise kernel at the horizon and recover the hot flat space result at infinity. Knowledge of the noise kernel is essential for studying issues related to black hole horizon fluctuations and Hawking radiation backreaction. We show that the Gaussian approximated Green function which works surprisingly well for the stress tensor at the Schwarzschild horizon produces significant error in the noise kernel there. We identify the failure as occurring at the fourth covariant derivative order.Comment: 21 pages, RevTeX

Immunomagnetic t-lymphocyte depletion (ITLD) of rat bone marrow using OX-19 monoclonal antibody

Graft versus host disease (GVHD) may be abrogated and host survival prolonged by in vitro depletion of T lymphocytes from bone marrow (BM) prior to allotransplantation. Using a mouse anti-rat pan T-lymphocyte monoclonal antibody (0×19) bound to monosized, magnetic, polymer beads, T lymphocytes were removed in vitro from normal bone marrow. The removal of the T lymphocytes was confirmed by flow cytometry. Injection of the T-lymphocyte-depleted bone marrow into fully allogeneic rats prevents the induction of GVHD and prolongs host survival. A highly efficient technique of T-lymphocyte depletion using rat bone marrow is described. It involves the binding of OX-19, a MoAb directed against all rat thy-mocytes and mature peripheral T lymphocytes, to monosized, magnetic polymer spheres. Magnetic separation of T lymphocytes after mixing the allogeneic bone marrow with the bead/OX-19 complex provides for a simple, rapid depletion of T lymphocytes from the bone marrow. In vitro studies using flow cytometry and the prevention of GVHD in a fully allogeneic rat bone marrow model have been used to demonstrate the effectiveness of the depletion procedure. © 1989 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

microRNA miR-142-3p Inhibits Breast Cancer Cell Invasiveness by Synchronous Targeting of WASL, Integrin Alpha V, and Additional Cytoskeletal Elements

MicroRNAs (miRNAs, micro ribonucleic acids) are pivotal post-transcriptional regulators of gene expression. These endogenous small non-coding RNAs play significant roles in tumorigenesis and tumor progression. miR-142-3p expression is dysregulated in several breast cancer subtypes. We aimed at investigating the role of miR-142-3p in breast cancer cell invasiveness. Supported by transcriptomic Affymetrix array analysis and confirmatory investigations at the mRNA and protein level, we demonstrate that overexpression of miR-142-3p in MDA-MB-231, MDA-MB-468 and MCF-7 breast cancer cells leads to downregulation of WASL (Wiskott-Aldrich syndrome-like, protein: N-WASP), Integrin-αV, RAC1, and CFL2, molecules implicated in cytoskeletal regulation and cell motility. ROCK2, IL6ST, KLF4, PGRMC2 and ADCY9 were identified as additional targets in a subset of cell lines. Decreased Matrigel invasiveness was associated with the miR-142-3p-induced expression changes. Confocal immunofluorescence microscopy, nanoscale atomic force microscopy and digital holographic microscopy revealed a change in cell morphology as well as a reduced cell volume and size. A more cortical actin distribution and a loss of membrane protrusions were observed in cells overexpressing miR-142-3p. Luciferase activation assays confirmed direct miR-142-3p-dependent regulation of the 3’-untranslated region of ITGAV and WASL. siRNA-mediated depletion of ITGAV and WASL resulted in a significant reduction of cellular invasiveness, highlighting the contribution of these factors to the miRNA-dependent invasion phenotype. While knockdown of WASL significantly reduced the number of membrane protrusions compared to controls, knockdown of ITGAV resulted in a decreased cell volume, indicating differential contributions of these factors to the miR-142-3p-induced phenotype. Our data identify WASL, ITGAV and several additional cytoskeleton-associated molecules as novel invasion-promoting targets of miR-142-3p in breast cancer