Fluorescence‐guided cancer surgery—A new paradigm Thammineedi, Subramanyeshwar Rao; Saksena, Ajesh Raj; Nusrath, Syed ...
Journal of surgical oncology,
05/2021, Letnik:
123, Številka:
8
Journal Article
Recenzirano
Fluorescence‐guided surgery is an emerging and promising operative adjunct to assist the surgeon in various aspects of oncosurgery, ranging from assessing perfusion, identification, and ...characterization of tumors and peritoneal metastases, mapping of lymph nodes/leaks, and assistance for fluorescence‐guided surgery (FGS). This study aims to provide an overview of principles, currently available dyes, platforms, and surgical applications and summarizes the available literature on the utility of FGS with a focus on abdomino‐thoracic malignancies.
This 36-month, randomized, parallel-group study compared safety and efficacy of two doses of everolimus with mycophenolate mofetil (MMF) in de novo renal-transplant recipients.
Renal-allograft ...recipients received 1.5 mg/day or 3 mg/day of everolimus or 2 g/day of MMF, plus full-dose cyclosporine (CsA) and corticosteroids after randomization. For at least their first year, patients received study medication according to a double-blinded, double-dummy design. Concerns over nephrotoxicity led to a protocol amendment to an open-label design with reduced CsA troughs.
Incidences of primary efficacy failure at 36 months (biopsy-proven acute rejection, graft loss, death, or loss to follow-up) were everolimus 1.5 mg/day, 33.7% (65/193); everolimus 3 mg/day, 34.0% (66/194); and MMF, 31.1% (61/196) (P=0.810). Antibody-treated acute rejection at 36 months was significantly lower with everolimus 1.5 mg (9.8%) than MMF (18.4%, P=0.014). Discontinuation for adverse events was more frequent with everolimus and hemolytic uremic syndrome, lymphoproliferative disease, and proteinuria, and higher serum creatinine occurred at increased frequency relative to the MMF arm. Creatinine levels in the everolimus arms were stable in follow-up: the mean rise in creatinine over the first 6 months of the open-label phase was 3 micromol/L or greater with everolimus and 7 micromol/L with MMF. However, serum creatinine levels were lower in the MMF group throughout. Death and graft loss were higher in the everolimus arms (not significant).
As part of triple-drug immunosuppression, everolimus (1.5 or 3 mg/day) was as efficacious as MMF, although the side-effect profile featured increased adverse events. Nephrotoxicity/calcineurin-inhibitor-related adverse events will require judicious lowering of CsA exposure with monitoring of everolimus troughs.
The 93-residue transmembrane protein CrgA in Mycobacterium tuberculosis is a central component of the divisome, a large macromolecular machine responsible for cell division. Through interactions with ...multiple other components including FtsZ, FtsQ, FtsI (PBPB), PBPA, and CwsA, CrgA facilitates the recruitment of the proteins essential for peptidoglycan synthesis to the divisome and stabilizes the divisome. CrgA is predicted to have two transmembrane helices. Here, the structure of CrgA was determined in a liquid–crystalline lipid bilayer environment by solid-state NMR spectroscopy. Oriented-sample data yielded orientational restraints, whereas magic-angle spinning data yielded interhelical distance restraints. These data define a complete structure for the transmembrane domain and provide rich information on the conformational ensembles of the partially disordered N-terminal region and interhelical loop. The structure of the transmembrane domain was refined using restrained molecular dynamics simulations in an all-atom representation of the same lipid bilayer environment as in the NMR samples. The two transmembrane helices form a left-handed packing arrangement with a crossing angle of 24° at the conserved Gly39 residue. This helix pair exposes other conserved glycine and alanine residues to the fatty acyl environment, which are potential sites for binding CrgA’s partners such as CwsA and FtsQ. This approach combining oriented-sample and magic-angle spinning NMR spectroscopy in native-like lipid bilayers with restrained molecular dynamics simulations represents a powerful tool for structural characterization of not only isolated membrane proteins, but their complexes, such as those that form macromolecular machines.
Significance Understanding the structure and function of the cell division apparatus of Mycobacterium tuberculosis is crucial for advancing drug development against tuberculosis. Here, we report the solid-state NMR structure of a transmembrane protein, CrgA, that is a central component of the M. tuberculosis divisome. Small helical membrane protein structures are particularly sensitive to their environment, and consequently, we characterized CrgA in an environment that models well the biophysical properties of the native membrane. To determine the structure, both oriented sample and magic-angle spinning NMR data from liquid–crystalline lipid bilayer preparations were used along with refinement by restrained molecular dynamics simulations in the same lipid environment. The structure suggests how CrgA serves as a platform for binding and recruiting other proteins of the divisome.
Numerical modeling of complex geometries necessitates the use of curvilinear body fitted coordinates. This article proposes a novel mixed basis formulation of the governing conservation equations for ...general curvilinear non-orthogonal grids with the physical covariant velocity as the primary solution variable. This results in an algorithm which has many advantages of orthogonal equations. The conservation equations written in this form retains the diagonal dominance of the pressure equation. The newly formed conservation equations are solved on a structured grid using the SIMPLER algorithm and are shown to converge well for non-orthogonal grids. Standard K–ϵ model is used for the turbulence closure.
Extending the Presic type operators to modular spaces, we introduce generalised Presic type w-contractive mappings and strongly w-contractive mappings in a modular metric space and establish ...fixed-point theorems for such contractions in modular spaces. Ulam–Hyers stability of the fixed-point equation involving Presic type operators is also discussed. Our results extend and generalise some known results in the literature. The results are supported by appropriate example and an application to Caratheodory type integral equation.
We describe a new method of fabricating large-area, highly scalable, “hybrid” superhydrophobic surfaces on silicon (Si) substrates with tunable, spatially selective adhesion behavior by controlling ...the morphologies of Si nanowire arrays. Gold (Au) nanoparticles were deposited on Si by glancing-angle deposition, followed by metal-assisted chemical etching of Si to form Si nanowire arrays. These surfaces were chemically modified and rendered hydrophobic by fluorosilane deposition. Au nanoparticles with different size distributions resulted in the synthesis of Si nanowires with very different morphologies (i.e., clumped and straight nanowire surfaces). The difference in nanowire morphology is attributed to capillary force-induced nanocohesion, which is due to the difference in nanowire porosity. The clumped nanowire surface demonstrated the lotus effect, and the straighter nanowires demonstrated the ability to pin water droplets while maintaining large contact angles (i.e., the petal effect). The high contact angles in both cases are explained by invoking the Cassie−Baxter wetting state. The high adhesion behavior of the straight nanowire surface may be explained by a combination of attractive van der Waals forces and capillary adhesion. We demonstrate the spatial patterning of both low- and high-adhesion superhydrophobicity on the same substrate by the simultaneous synthesis of clumped and straight silicon nanowires. The demonstration of hybrid superhydrophobic surfaces with spatially selective, tunable adhesion behavior on single substrates paves the way for future applications in microfluidic channels, substrates for biologically and chemically based analysis and detection where it is necessary to analyze a particular droplet in a defined location on a surface, and as a platform to study in situ chemical mixing and interfacial reactions of liquid pearls.
Leukocyte function associated antigen‐1 (LFA‐1) has a multifaceted role in the immune response, including adhesion and trafficking of leukocytes, stabilizing the immune synapse of the MHC‐TCR complex ...and providing costimulation signals. Monoclonal antibodies to the CD11a chain of LFA‐1 have been seen to result in effective immunosuppression in experimental models. Efalizumab, a humanized IgG1 anti‐CD11a, is approved for use in psoriasis and may provide effective immunosuppression in organ transplantation. Thirty‐eight patients undergoing their first living donor or deceased renal transplant were randomized to receive efalizumab 0.5 or 2 mg/kg weekly subcutaneously for 12 weeks. Patients were maintained on full dose cyclosporine, mycophenolate mofetil and steroids or half dose cyclosporine, sirolimus and prednisone. At 6 months following transplant patient survival was 97% and graft survival was 95%. Clinical biopsy‐proven acute rejection in the first 6 months after transplantation was confirmed in 4 of 38 patients (11%). Three patients (8%) developed post transplant lymphoproliferative disease, all treated with the higher dose efalizumab and full dose cyclosporine. The two doses of efalizumab resulted in comparable saturation and modulation of CD11a. This phase II trial suggests that efalizumab may warrant further investigation in transplantation.
In this phase I/II trial of efalizumab (anti‐LFA‐1), 3 of 38 patients (8%) developed post‐transplant lymphoproliferative disease, all receiving high dose efalizumab and full dose cyclosporine in this phase I/II randomized trial.
The synthesis of a novel composite adsorbent prepared from coir pith activated carbon (CPAC), chitosan and sodium dodecyl sulphate (SDS, an anionic surfactant) is reported. The characterisation of ...the composite was done using SEM, XRD, UV–visible and IR spectroscopy studies. The effectiveness of the composite was made for the removal of a toxic cationic dye, malachite green (MG) from waste water based on adsorption studies. The reaction conditions for the adsorption studies were optimized based on initial dye concentration, dose rate, reaction time, pH and temperature. Langmuir and Freundlich isotherm models were adopted to study the mechanism of adsorption. The adsorption process was found to follow pseudo second order kinetics. The results of the present study indicate that the CPAC based composite could be an effective low cost adsorbent for the removal of MG from waste water.
PDF
