Summary
Although different injection locations for retrolaminar and erector spinae plane blocks have been described, the two procedures have a similar anatomical basis. In this cadaveric study we ...compared anatomical spread of dye in the thoracic region following these two procedures. Following randomisation, 10 retrolaminar blocks and 10 erector spinae plane blocks were performed on the left or right sides of 10 unembalmed cadavers. For each block, 20 ml of dye solution was injected at the T5 level. The back regions were dissected and the involvement of the thoracic spinal nerve was also investigated. Twenty blocks were successfully completed. A consistent vertical spread, with deep staining between the posterior surface of the vertebral laminae and the overlaying transversospinalis muscle was observed in all retrolaminar blocks. Moreover, most retrolaminar blocks were predominantly associated with fascial spreading in the intrinsic back muscles. With an erector spinae plane block, dye spread in a more lateral pattern than with retrolaminar block, and fascial spreading in the back muscles was also observed. The number of stained thoracic spinal nerves was greater with erector spinae plane blocks than with retrolaminar blocks; median 2.0 and 3.5, respectively. Regardless of technique, the main route of dye spread was through the superior costotransverse ligament to the ipsilateral paravertebral space. Although erector spinae plane blocks were associated with a slightly larger number of stained thoracic spinal nerves than retrolaminar blocks, both techniques were consistently associated with posterior spread of dye and with limited spread to the paravertebral space.
ABSTRACT Galactic outflows play an important role in galactic evolution. Despite their importance, a detailed understanding of the physical mechanisms responsible for the driving of these winds is ...lacking. In an effort to gain more insight into the nature of these flows, we perform global three-dimensional magnetohydrodynamical simulations of an isolated Milky Way-size starburst galaxy. We focus on the dynamical role of cosmic rays (CRs) injected by supernovae, and specifically on the impact of the streaming and anisotropic diffusion of CRs along the magnetic fields. We find that these microphysical effects can have a significant effect on the wind launching and mass loading factors, depending on the details of the plasma physics. Due to the CR streaming instability, CRs propagating in the interstellar medium scatter on self-excited Alfvén waves and couple to the gas. When the wave growth due to the streaming instability is inhibited by some damping process, such as turbulent damping, the coupling of CRs to the gas is weaker and their effective propagation speed faster than the Alfvén speed. Alternatively, CRs could scatter from "extrinsic turbulence" that is driven by another mechanism. We demonstrate that the presence of moderately super-Alfvénic CR streaming enhances the efficiency of galactic wind driving. Cosmic rays stream away from denser regions near the galactic disk along partially ordered magnetic fields and in the process accelerate more tenuous gas away from the galaxy. For CR acceleration efficiencies broadly consistent with the observational constraints, CRs reduce the galactic star formation rates and significantly aid in launching galactic winds.
The unique characteristic of head and neck squamous cell carcinoma (HNSCC) is that local invasion rather than distant metastasis is the major route for dissemination. Therefore, targeting the locally ...invasive cancer cells is more important than preventing systemic metastasis in HNSCC and other invasive-predominant cancers. We previously demonstrate a specific mechanism for HNSCC local invasion: the epithelial-mesenchymal transition (EMT) regulator Twist1 represses microRNA let-7i expression, leading to the activation of the small GTPase Rac1 and engendering the mesenchymal-mode movement in three-dimensional (3D) culture. However, targeting the EMT regulator is relatively difficult because of its transcription factor nature and the strategy for confining HNSCC invasion to facilitate local treatment is limited. Imipramine blue (IB) is a newly identified anti-invasive compound that effectively inhibits glioma invasion. Here we demonstrate that in HNSCC cells, a noncytotoxic dose of IB represses mesenchymal-mode migration in two-and-a-half-dimensional/3D culture system. IB suppresses EMT and stemness of HNSCC cells through inhibition of Twist1-mediated let-7i downregulation and Rac1 activation and the EMT signalling. Mechanistically, IB inhibits reactive oxygen species-induced nuclear factor-κB pathway activation. Importantly, IB promotes degradation of the EMT inducer Twist1 by enhancing F-box and leucine-rich repeat protein 14 (FBXL14)-mediated polyubiquitination of Twist1. Together, this study demonstrates the potent anti-invasion and EMT-inhibition effect of IB, suggesting the potential of IB in treating local invasion-predominant cancers.
Abstract
Front-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) therapy is the standard of care for lung cancer patients with sensitising EGFR mutations (exon 19 deletion or ...L858R mutation). Several phase III studies have demonstrated the superiority of gefitinib, erlotinib (first generation of TKIs) or afatinib (second generation) to chemotherapy in progression-free survival and response rates. Drug-related toxicities, such as diarrhoea, acneiform skin rash, mucositis, and paronychia, are frequently encountered in patients who receive EGFR TKIs. Other rare side-effects, such as hepatic impairment and interstitial lung disease, should be identified early and managed carefully. Patients with uncommon EGFR mutations, such as G719X, S768I, and L861Q, may require special selection of EGFR TKIs. The combination of erlotinib plus bevacizumab has been accepted in certain parts of the world as an alternative front-line treatment. This review article summarizes the studies leading to the establishment of EGFR TKIs in EGFR-mutant lung cancer patients. The side-effect profiles of the current EGFR TKIs in these large trials are listed, and the management of uncommon EGFR mutations is discussed. Finally, the potential role of combination front-line treatment is discussed.
ABSTRACT Feedback from the active galactic nuclei (AGNs) is one of the most promising heating mechanisms to circumvent the cooling-flow problem in galaxy clusters. However, the role of thermal ...conduction remains unclear. Previous studies have shown that anisotropic thermal conduction in cluster cool cores (CCs) could drive the heat-flux-driven buoyancy instabilities (HBIs) that reorient the field lines in the azimuthal directions and isolate the cores from conductive heating from the outskirts. However, how the AGN interacts with the HBI is still unknown. To understand these interwined processes, we perform the first 3D magnetohydrodynamic simulations of isolated CC clusters that include anisotropic conduction, radiative cooling, and AGN feedback. We find the following: (1) For realistic magnetic field strengths in clusters, magnetic tension can suppress a significant portion of HBI-unstable modes, and thus the HBI is either completely inhibited or significantly impaired, depending on the unknown magnetic field coherence length. (2) Turbulence driven by AGN jets can effectively randomize magnetic field lines and sustain conductivity at ∼1/3 of the Spitzer value; however, the AGN-driven turbulence is not volume filling. (3) Conductive heating within the cores could contribute to ∼10% of the radiative losses in Perseus-like clusters and up to ∼50% for clusters twice the mass of Perseus. (4) Thermal conduction has various impacts on the AGN activity and intracluster medium properties for the hottest clusters, which may be searched by future observations to constrain the level of conductivity in clusters. The distribution of cold gas and the implications are also discussed.
Saccharum spontaneum L. is one of the most important germplasm resources for modern sugarcane breeding. Exploring the cold tolerance of S. spontaneum clones with different ploidy levels and screening ...for cold‐tolerant material can be helpful in parent selection for breeding cold‐tolerant sugarcane.
Morphological indices, leaf ultrastructure and physiological indices were used to evaluate the cold tolerance of 36 S. spontaneum clones with different ploidy levels (2n = 40, 48, 54, 60, 64, 78, 80, 88, 92 and 96).
The morphological indices of S. spontaneum clones with different ploidy levels were positively correlated with ploidy. Under low‐temperature stress, the chloroplast and mitochondrial structures of the clones with high ploidy were more severely damaged than were those of clones with low ploidy. A comprehensive evaluation of the physiological indices showed that the 36 S. spontaneum clones could be divided into four categories: strongly cold tolerant, cold tolerant, moderately cold tolerant and cold sensitive. Correlation analysis of the morphological indices and cold tolerance revealed a significant negative correlation between cold tolerance and ploidy. On the basis of the morphological and physiological indices, optimal stepwise regression equations that can be used for the selection of cold‐tolerant S. spontaneum resources were established.
The S. spontaneum clones with low ploidy are more cold tolerant than those with high ploidy. Clones 12‐37, 13‐10 and 12‐23 are strongly cold‐tolerant germplasm resources, which suggests these germplasm sources have high potential for use in breeding cold‐tolerant sugarcane.
The morphological and physiological indexes of 36 S. spontaneum clones with 10 different ploidy levels showed that S. spontaneum clones with low ploidy are more cold tolerant than those with high ploidy.
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