Navigated percutaneous versus open pedicle screw implantation using intraoperative CT and robotic cone-beam CT imaging

Percutaneous paraspinal pedicle screw implantation (PPSI) reduces soft tissue trauma, blood loss, and postoperative pain but remains technically challenging and associated with radiation exposure and implant-related artefacts. Here, we determined the feasibility, screw accessibility, and the accuracy of navigated PPSI in the thoraco-lumbar sacral spine using intraoperative computed tomography (iCT) and robotic cone-beam CT (CBCT) imaging. Between 2015 and 2018, 465 percutaneous paraspinal pedicle screws were implanted in 75 patients using iCT- or CBCT-based spinal navigation with 230 screws connected to rod reducers during screw assessment imaging (iCT 198; CBCT 32). Clinical and demographic data, intraoperative screw accessibility, and screw accuracy were analyzed and compared to a case-matched cohort of 75 patients undergoing navigated implantation of 481 pedicle screws through an open midline approach. Both iCT and CBCT permitted reliable assessment of each implanted screw, regardless of artifacts caused by rod reducers. Although overall accuracy for correct placement was comparable between PPSI and open surgery (PPSI 96.6%; Open 94.2%), PPSI compared favorably to open surgery regarding complete placement within the pedicle (PPSI 90.1%; Open 75.1%; p  <  0.0001), regional placement accuracy in the lumbar (PPSI 97.8%; Open 91.5%; p  <  0.001), and lumbar-sacral spine (PPSI 100%; Open 81.2%; p  <  0.05), next to the duration of surgery and length of hospitalization. PPSI with iCT- and CBCT-based spinal navigation improves the accuracy, safety, and workflow of navigated spinal instrumentation. Next, a cost-effectiveness and outcome analysis should determine whether iCT and CBCT imaging are truly economically justified. These slides can be retrieved under Electronic Supplementary Material.     

Surgical ventricular reconstruction and subendocardial resection for the treatment of refractory ventricular tachycardia

We describe a case of 64-year-old female patient with ventricular tachycardia intractable to medical treatment and acute heart failure following myocardial infarction. Emergency surgical ventricular reconstruction and subendocardial resection was undertaken. We discuss the option of surgical intervention in this difficult and unusual clinical scenario.     

CT/MR LI-RADS 2018: clinical implications and management recommendations

Abdominal Radiology - Unique among solid organ tumors, hepatocellular carcinoma (HCC), may be diagnosed by imaging alone, without the need for biopsy. The Liver Imaging Reporting and Data System...     

Chemical Modifications of Transfer RNA Species. Desulfurization with Raney Nickel

A single, modified nucleoside in Escherichia coli tRNA, 6-(3-methyl-2-butenylamino)-2-methyl-thio-9-beta-D-ribofuranosylpurine, has been desulfurized with Raney nickel to afford its probable biosynthetic precursor. The limitations of the reaction at the nucleoside and tRNA levels and its lack of inhibition of the amino acid acceptor activity of tRNA are described.     

Differing roles of protein kinase C-zeta in disruption of tight junction barrier by enteropathogenic and enterohemorrhagic Escherichia coli

BACKGROUND & AIMS: Enteropathogenic Escherichia coli and enterohemorrhagic E. coli harbor highly homologous pathogenicity islands yet show key differences in their mechanisms of action. Both disrupt host intestinal epithelial tight junctions, but the effects of enteropathogenic E. coli are more profound than those of enterohemorrhagic E. coli. The basis for this is not understood. The atypical protein kinase C isoform, protein kinase C-zeta, associates with and regulates the tight junction complex. The aim of this study was to compare the role of protein kinase C-zeta in the disruption of tight junctions after infection with enteropathogenic E. coli and enterohemorrhagic E. coli. METHODS: Model intestinal epithelial monolayers infected by enteropathogenic E. coli or enterohemorrhagic E. coli were used for these studies. RESULTS: Neither bisindolylmaleimide nor G?6976, which block several protein kinase C isoforms but not protein kinase C-zeta, protected against the decrease in transepithelial electrical resistance after enteropathogenic E. coli infection. Rottlerin at concentrations that block novel and atypical isoforms, including protein kinase C-zeta, significantly attenuated the decrease in transepithelial electrical resistance. The specific inhibitory peptide, myristoylated protein kinase C-zeta pseudosubstrate, also significantly decreased the enteropathogenic E. coli -associated decrease in transepithelial electrical resistance and redistribution of tight junction proteins. In contrast to enteropathogenic E. coli, the level of protein kinase C-zeta enzyme activity stimulated by enterohemorrhagic E. coli was transient and minor, and protein kinase C-zeta inhibition had no effect on the decrease in transepithelial electrical resistance or the redistribution of occludin. CONCLUSIONS: The differential regulation of protein kinase C-zeta by enteropathogenic E. coli and enterohemorrhagic E. coli may in part explain the less profound effect of the latter on the barrier function of tight junctions.     

Dose-response study of the carcinogenicity of tobacco-specific N-nitrosamines in F344 rats

Summary Tobacco and tobacco smoke contain relatively high amounts of four tobacco-specific N-nitrosamines. Of these, N-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and N-nitrosoanatabine (NAT) were bioassayed at three dose levels by subcutaneous injections into male and female F344 rats in 60 subdoses amounting in total to 9, 3, and 1 mmol/kg. Compared with the solvent control group (trioctanoin), both NNN and NNK induced significant numbers of tumors of the nasal cavity (P<0.01) at all three dose levels in both male and female rats. Significant numbers of tumors were also induced by NNK in the lung at all three dose levels and in the liver at the highest dose level (P<0.05). In addition to nasal tumors NNN also induced esophageal tumors at a significant rate in male rats at the high and medium dose levels and in female rats at the high level (P<0.05); NAT was inactive at the three doses tested. Bioassays at lower dose levels as well as biochemical studies are strongly indicated for NNN and NNK since these nitrosamines occur in relatively high amounts in both chewing tobacco and tobacco smoke.Abbreviations HPLC high performance liquid chromatography - NAB N-nitrosoanabasinc - NAT N-nitrosoanatabine - NNK 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone - NNN N-nitrosonornicotine Dedicated to Professor Hermann Druckrey on the occasion of his 80th birthdayThis is No. XXVII of A Study of Tobacco Carcinogenesis. The study is supported by U.S. National Cancer Institute Grant CA-29580We thank Ms. Maria Nicholais and Mr. Joel Reinhardt from the Research Animal Facility for their excellent technical assistance     

Solution structure of a de novo protein from a designed combinatorial library

Combinatorial libraries of de novo amino acid sequences can provide a rich source of diversity for the discovery of novel proteins. Randomly generated sequences, however, rarely fold into well ordered protein-like structures. To enhance the quality of a library, diversity must be focused into those regions of sequence space most likely to yield well folded structures. We have constructed focused libraries of de novo sequences by designing the binary pattern of polar and nonpolar amino acids to favor structures that contain abundant secondary structure, while simultaneously burying hydrophobic side chains in the protein interior and exposing hydrophilic side chains to solvent. Because binary patterning specifies only the polar/nonpolar periodicity, but not the identities of the side chains, detailed structural features, including packing interactions, cannot be designed a priori. Can binary patterned libraries nonetheless encode well folded proteins? An unambiguous answer to this question requires determination of a 3D structure. We used NMR spectroscopy to determine the structure of S-824, a novel protein from a recently constructed library of 102-residue sequences. This library is "na?ve" in that it has not been subjected to high-throughput screens or directed evolution. The experimentally determined structure of S-824 is a four-helix bundle, as specified by the design. As dictated by the binary-code strategy, nonpolar side chains are buried in the protein interior, and polar side chains are exposed to solvent. The polypeptide backbone and buried side chains are well ordered, demonstrating that S-824 is not a molten globule and forms a unique structure. These results show that amino acid sequences that have neither been selected by evolution, nor designed by computer, nor isolated by high-throughput screening, can form native-like structures. These findings validate the binary-code strategy as an effective method for producing vast collections of well folded de novo proteins.     

Differential coupling of CC chemokine receptors to multiple heterotrimeric G proteins in human interleukin-2-activated natural killer cells

Using two different approaches, we have investigated the types of G proteins coupled to CC chemokine receptors. First, permeabilization of interleukin-2-activated natural killer (IANK) cells with streptolysin-O and introduction of anti-G protein antibodies inside these cells resulted in the following. (1) Anti-G(s), anti-G(o), and anti-G(z) inhibited the migration of IANK cells in response to macrophage- inflammatory protein-1 alpha (MIP-1 alpha), monocyte chemoattractant protein-1 (MCP-1), or regulated on activation normal T cell expressed and secreted (RANTES). (2) Anti-Gi inhibited their migration in response to MCP-1 or RANTES but not in response to MIP-1 alpha. Second, incubation of IANK cell membranes with anti-G protein antibodies before incubating with (gamma-35S) GTP or (gamma-32P) GTP, resulted in the following. (1) Anti-G(s), anti-G(o), or anti-G(z) inhibited GTP binding and GTPase activity in the presence of MIP-1 alpha, or RANTES. (2) Anti- G(i) inhibited GTP binding and GTPase activity in the presence of MCP-1 or RANTES but not in the presence of MIP-1 alpha. The inhibitory effect of anti-G protein antibodies was reversed upon incubating these antibodies with their respective synthetic peptides before addition to IANK cell membranes. These results suggest that MCP-1 and RANTES receptors are promiscuously coupled to multiple G proteins in IANK cell membranes and that this coupling is different from MIP-1 alpha receptors, which seem to be coupled to G(s), G(o), and G(z) but not to G(i).