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Background: Femoral nerve block (FNB) is a commonly performed technique that has been proven to provide effective regional analgesia after anterior cruciate ligament (ACL) reconstruction. The adductor canal block (ACB) uses a similar sensory block around the knee while avoiding motor blockade of the quadriceps muscles. Purpose/Hypothesis: The purpose of our study was to compare the efficacy of FNB versus ACB for pain control after ACL reconstruction. It was hypothesized that there would be no difference in pain levels or opioid requirements between the 2 groups. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: We performed a prospective, double-blinded, randomized controlled trial. Sixty patients undergoing primary ACL reconstruction with bone-patellar tendon-bone autograft were randomized to receive either an ACB or an FNB preoperatively. The primary outcomes assessed were pain levels (visual analog scale) and narcotic requirements for 4 days after surgery. Secondary outcomes included ability to perform a straight leg raise in the recovery room and difference in thigh circumference between the operative and nonoperative leg measured at 7 days postoperatively. Results: Morphine requirements were less in the ACB group in the first 4 hours postoperatively ( P = .02). Aside from this time interval, no differences were found between the 2 groups with regard to opioid requirements and pain scores at any other time. Similarly, no differences were noted in patients’ ability to perform a straight leg raise in the recovery room ( P = .13) or in thigh circumference at the first postoperative visit ( P = .09). Conclusion: The results of our study suggest similar efficacy in perioperative pain control with the use of an ACB for ACL reconstruction when compared with FNB. The potential long-term benefit of quadriceps preservation with the ACB is worthy of future study. Registration: NCT03033589 (ClinicalTrials.gov identifier).

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Immune suppression mediated by exosomes is an emerging concept with potentially immense utility for immunotherapy in a variety of inflammatory contexts, including allogeneic transplantation. Exosomes containing the apoptosis-inducing molecule Fas ligand (FasL) have demonstrated efficacy in inhibiting antigen-specific immune responses upon adoptive transfer in animal models. We report here that a very high frequency of human B cell-derived lymphoblastoid cell lines (LCL) constitutively produce MHCII+FasL+ exosomes that can induce apoptosis in CD4+ T cells. All LCL tested for this study (>20 independent cell lines) showed robust expression of FasL, but had no detectable FasL on the cell surface. Given this intracellular sequestration, we hypothesized that FasL in LCL was retained in the secretory lysosome and secreted via exosomes. Indeed, we found both MHCII and FasL proteins present in LCL-derived exosomes, and using a bead-based exosome capture assay demonstrated the presence of MHCII+FasL+ exosomes among those secreted by LCL. Using two independent experimental approaches, we demonstrated that LCL-derived exosomes were capable of inducing antigen-specific apoptosis in autologous CD4+ T cells. These results suggest that LCL-derived exosomes may present a realistic source of immunosuppressive exosomes that could reduce or eliminate T cell-mediated responses against donor-derived antigens in transplant recipients.

These findings may inform future pitching recommendations with intentions of curtailing medial elbow injuries experienced by young pitchers, such as ulnar collateral ligament injuries.

This paper focuses on the ability of a folate-decorated triblock copolymer to deliver a targeted dose of siRNA in order to overcome chemotherapy resistance which can commonly cause complications in ovarian cancer patients. The micelleplexes that are formed upon electrostatic interaction with siRNA are used to deliver siRNA in a targeted manner to SKOV-3 ovarian cancer cells that overexpress folate receptor-α (FRα). The triblock copolymer consists of polyethylenimine-graft-polycaprolactone-block-poly(ethylene glycol) (PEI-g-PCL-b-PEG-Fol). In this work, polymers of different molecular weights of PEG, as well as different grafting degrees of the (g-PCL-b-PEG-Fol) chains to PEI, were analyzed to optimize targeted siRNA delivery. The polymers, their micelleplexes, and the in vitro performance of the latter were characterized by nuclear magnetic resonance, dynamic light scattering, transmission electron microscopy, flow cytrometry, western blot, confocal microscopy, and in luciferase assays. The different PEI-g-PCL-b-PEG-Fol conjugates showed suitable sizes below 260 nm, especially at N/P 5, which also allowed for full siRNA condensation. Furthermore, flow cytometry and Western blot analysis demonstrated that our best polymer was able to effectively deliver siRNA and that siRNA delivery resulted in efficient protein knockdown of toll-like receptor 4 (TLR4). Consequently, TLR4 knock down within SKOV-3 cells resensitized them toward paclitaxel (PTX) treatment, and apoptotic events increased. This study demonstrates that PEI-g-PCL-b-PEG-Fol conjugates are a reliable delivery system for siRNA and are able to mediate therapeutic protein knockdown within ovarian cancer cells. Additionally, this study provides further evidence to link TLR4 levels to chemotherapy resistance.

In this simulated game analysis, pitchers experienced increased fatigue after each successive inning. While the average pitch velocity declined with each successive inning, the torque on the medial elbow increased after inning 3. These findings signify a possible relationship between fatigue and injury risk.

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