A Comparative Study of Ultrasound-Guided Continuous Adductor Canal Block With Ultrasound-Guided Continuous Femoral Nerve Block in Unilateral Total Knee Arthroplasty for Limb Mobilization and Analgesic Efficacy.

Background Total knee joint replacement surgery is associated with severe postoperative pain and is amenable to regional anesthesia techniques for pain control. Femoral nerve block (FNB) provides effective analgesia after total knee arthroplasty (TKA) but has been associated with delayed ambulation due to quadriceps muscle weakness. Adductor canal block (ACB) may be a promising alternative, with less effect on the quadriceps muscle and comparable analgesic efficacy. We evaluated the effectiveness, safety, and patient satisfaction of continuous ACB augmented with infiltration between the popliteal artery and capsule of the knee (iPACK) block and compared them with those of continuous FNB amplified with iPACK block in preventing postoperative pain among patients undergoing unilateral total knee replacement (TKR) surgeries. Methodology According to a computer-generated sequence from September 2019 to June 2020, 50 American Society of Anesthesiologists grades I-III patients aged between 35 and 75 years who underwent unilateral TKR surgery were randomized into two equal groups, namely, ACB and FNB. The Timed Up and Go (TUG) and 10-minute walk tests were used to detect early ambulation (impact on quadriceps muscle). The secondary goal was to evaluate and compare opioid consumption and analgesic efficacy between the groups measured using a numeric rating scale (NRS). The demographic characteristics, technical difficulty, efficiency, safety, and comfort were compared between the two groups. Results During the postoperative period, patients in the ACB group could perform all TUG tests significantly faster than those in the FNB group. The mean get-up time in the ACB group was 39.08 ± 5.53 seconds, whereas that in the FNB group was 44.92 ± 7.10 seconds (p < 0.01). The 3-m walk time was 123.16 ± 15.90 seconds in the ACB group and 134.68 ± 13.13 seconds in the FNB group (p < 0.01). The 10-m walk time was 221.24 ± 18.82 seconds in the ACB group and 245.24 ± 21.68 seconds in the FNB group (p < 0.001). No significant difference was observed in NRS scores between the groups after the first 24 hours. The number of opioids available for consumption in both groups was equivalent. Conclusions ACB when augmented with an iPACK block is a good alternative to FNB for unilateral TKR surgeries. ACB may promote early ambulation without a reduction in analgesia when compared with FNB.

Identification of RAPD and SCAR markers associated with yield traits in the Indian tropical tasar silkworm Antheraea mylitta drury.

The tropical tasar silkworm, Antheraea mylitta, is a semi-domesticated vanya silk-producing insect of high economic importance. To date, no molecular marker associated with cocoon and shell weights has been identified in this species. In this report, we identified a randomly amplified polymorphic DNA (RAPD) marker and examined its inheritance, and also developed a stable diagnostic sequence-characterized amplified region (SCAR) marker. Silkworms were divided into groups with high (HCSW) and low (LCSW) cocoon and shell weights, and the F(2) progeny of a cross between these two groups were obtained. DNA from these silkworms was screened by PCR using 34 random primers and the resulting RAPD fragments were used for cluster analysis and discriminant function analysis (DFA). The clustering pattern in a UPGMA-based dendogram and DFA clearly distinguished the HCSW and LCSW groups. Multiple regression analysis identified five markers associated with cocoon and shell weights. The marker OPW16(905 bp) showed the most significant association with cocoon and shell weights, and its inheritance was confirmed in F(2) progeny. Cloning and sequencing of this 905 bp fragment showed 88% identity between its 134 nucleotides and the Bmc-1/Yamato-like retroposon of A. mylitta. This marker was further converted into a diagnostic SCAR marker (SCOPW 16(826 bp)). The SCAR marker developed here may be useful in identifying the right parental stock of tasar silk-worms for high cocoon and shell weights in breeding programs designed to enhance the productivity of tasar silk.

SWAP-70 regulates mast cell FcepsilonRI-mediated signaling and anaphylaxis.

Mast cells, perhaps best known by their ability to trigger allergic reactions after stimulation through the FcepsilonRI, express the unusual phosphatidylinositol 3-kinase (PI3K)-dependent, Rac-binding protein SWAP-70. Here, we show that the IgE-mediated passive cutaneous and the systemic anaphylactic responses are strongly reduced in SWAP-70(-/-) mice. Cultured SWAP-70(-/-) immature bone marrow mast cells (BMMC) are also impaired in FcepsilonRI-mediated degranulation, which can be restored by expression of exogenous wild-type SWAP-70, but less so if a phosphatidylinositol trisphosphate (PIP(3)) binding mutant is expressed. SWAP-70 itself supports inositol-3-phosphate and PIP(3) production, the latter indicating a potential feedback from SWAP-70 towards PI3K. FcepsilonRI-stimulated transcription and release of cytokines is controlled by SWAP-70. Key FcepsilonRI signal transduction events like activation of LAT by phosphorylation, activation of Akt/PKB and of p38 MAP kinase are reduced in SWAP-70(-/-) BMMC, but ERK is strongly hyperactivated. Some requirements for SWAP-70 were apparent only under limited-strength signaling conditions. We suggest that SWAP-70 defines a new element of efficient mast cell activation upon FcepsilonRI signaling, important for the control of mast cell-dependent anaphylaxis.

Immune reconstitution prevents metastatic recurrence of murine osteosarcoma.

Primary tumors developing in immunocompetent hosts escape immunosurveillance by acquiring immune evasive properties. This raises the prospect that metastases derived from such tumors will also evade immunity. To investigate whether immune surveillance plays a role in preventing metastases, we studied a murine model which mimics the clinical progression of osteosarcoma: primary tumor growth in the lower extremity, amputation, minimal residual disease followed by the development of overt metastases. K7M2 implants readily escaped immune surveillance since normal BALB/c mice, T cell deficient SCID and T/NK cell deficient SCID-bg mice showed no difference in the rate of growth of primary osteosarcomas. However, both SCID and SCID-bg mice had higher rates of metastases than immunocompetent mice. Similarly, immune reconstitution following transfer of naive T cells to SCID or SCID-bg mice did not impact primary tumor growth, but significantly diminished metastatic recurrence. T cells in osteosarcoma bearing mice produced IFNgamma in response to tumor and IFNgamma production by immune reconstituting T cells was required to prevent metastases. These results demonstrate an important role for T cell based immune surveillance in preventing metastases, even when metastases develop from tumors that adeptly evade immunosurveillance. The results further suggest that T cell depleting cancer therapies may eliminate beneficial immune responses and that immune reconstitution of lymphopenic cancer patients could prevent metastatic recurrence of solid tumors.

Flt3 ligand enhances thymic-dependent and thymic-independent immune reconstitution.

Despite recent progress in our understanding of the biology of T-cell homeostasis, clinically available therapies to substantially improve immune reconstitution in patients sustaining T-cell depletion are lacking. T cells are regenerated via a dynamic interplay between thymopoiesis and thymic-independent homeostatic peripheral expansion (HPE). Using athymic mice subjected to T-cell depletion, we observed that HPE is critically dependent on dendritic cells (DCs) for presentation of antigen, raising the possibility that the availability of DCs might be limiting in vivo for HPE to occur efficiently. Indeed, flt3 ligand (flt3L) treatment of athymic mice subjected to T-cell depletion (without DC depletion) substantially enhanced HPE and improved immune competence. Following bone marrow transplantation (BMT) in athymic hosts, both dendritic cells and T cells were profoundly depleted and flt3L therapy restored DC numbers and enhanced HPE. In addition, thymus-bearing BMT recipients treated with flt3L regenerated increased numbers of thymic-dependent progeny with increased numbers of T-cell receptor excision circle (TREC)-positive T cells, indicating increased thymopoiesis. Therefore, flt3L is a potent immunorestorative agent that enhances both thymic-dependent and thymic-independent pathways of T-cell regeneration.

Interleukin 7 worsens graft-versus-host disease.

Impaired immune reconstitution has moved to the forefront of clinical problems limiting progress in allogeneic bone marrow transplantation (BMT). The identification of therapies that can enhance immune reconstitution by increasing thymopoiesis is critical to solving this problem. Interleukin 7 (IL-7) is the most potent thymopoietic cytokine identified thus far. To study the effects of IL-7 on immune reconstitution and graft-versus-host disease (GVHD) following allogeneic BMT, we administered recombinant human IL-7 (rhIL-7) in a murine parent into an F1 model. Results showed that rhIL-7 therapy lowered the "threshold" T-cell dose required to induce both clinical signs of GVHD as well as lethal GVHD. Histologic analysis of GVHD target tissues revealed that rhIL-7 increased the degree of inflammation and tissue damage observed at all T-cell doses studied, but did not change the pattern of organs affected or the histologic appearance of the GVHD within target organs. In addition, we evaluated the capacity for rhIL-7 to enhance thymopoiesis in the setting of allogeneic T cell-depleted (TCD) and T-cell-replete BMT. We observed that rhIL-7 therapy enhanced thymic function in TCD allogeneic BM transplant recipients, but not in animals that received even modest doses of T cells presumably due to thymic toxicity of the graft-versus-host reaction. Thus, caution must be exercised as IL-7 is developed clinically as an immunorestorative agent for use in the setting of allogeneic BMT. These results suggest that use of IL-7 should be limited to the setting of TCD BMT to obtain the greatest benefit on immune competence with the least toxicity.