Effect of atherothrombotic aorta on outcomes of total aortic arch replacement

ObjectiveThe effect of an atherothrombotic aorta on the short- and long-term outcomes of total aortic arch replacement, including postoperative neurologic deficits, remains unknown. We evaluated this relationship and also elucidated the synergistic effect of multiple other risk factors, in addition to an atherothrombotic aorta, on the neurologic outcome.MethodsA group of 179 consecutive patients undergoing total aortic arch replacement were studied. An atherothrombotic aorta was present in 34 patients (19%), more than moderate leukoaraiosis in 71 (39.7%), and significant extracranial carotid artery stenosis in 27 (15.1%). In-hospital deaths occurred in 2 patients, 1 (2.9%) of 34 patients with and 1 (0.7%) of 145 patients without an atherothrombotic aorta (P = .26). Permanent neurologic deficits occurred in 4 (2.2%) and transient neurologic deficits in 17 (9.5%) patients. Multivariate analysis demonstrated that the risk factors for transient neurologic deficits were an atherothrombotic aorta (odds ratio, 4.4), extracranial carotid artery stenosis (odds ratio, 5.5), moderate/severe leukoaraiosis (odds ratio, 3.6), and cardiopulmonary bypass time (odds ratio, 1.02). To calculate the probability of transient neurologic deficits, the following equation was derived: probability of transient neurologic deficits = {1 + exp [7.276 − 1.489 (atherothrombotic aorta) − 1.285 (leukoaraiosis) − 1.701 (extracranial carotid artery stenosis) − 0.017 (cardiopulmonary bypass time)]}−1. An exponential increase occurred in the probability of transient neurologic deficits with presence of an atherothrombotic aorta and other risk factors in relation to the cardiopulmonary bypass time. Survival at 3 years after surgery was significantly reduced in patients with vs without an atherothrombotic aorta (75.0% ± 8.8% vs 89.2% ± 3.1%, P = .01).ConclusionsPatients with an atherothrombotic aorta and associated preoperative comorbidities might be predisposed to adverse short- and long-term outcomes, including transient neurologic deficits

Evidence of mature adipocyte proliferation regulated by proliferin

Despite much research, whether mature adipocytes proliferate remains controversial. Here, we examined 5-bromo-2′-deoxyuridine (BrdU)-labelling of mature adipocytes. Although BrdU incorporation into subcutaneous adipocytes was less than that in visceral adipocytes, pioglitazone (Pio) treatment increased BrdU incorporation in subcutaneous, but not visceral, adipocytes in rats. Fully differentiated 3T3-L1 adipocytes exhibited an increase in cell number and BrdU incorporation with time, with this increase enhanced by Pio treatment. We therefore screened for genes that encode growth factors regulated by Pio, and selected proliferin (PLF). Both gene silencing of PLF by small interfering RNA and treatment with anti-PLF antibody suppressed proliferation in 3T3-L1 adipocytes. In adipocytes isolated from Pio-treated rats, the tissue-specific pattern of PLF expression was similar to that of BrdU incorporation. Administration of an anti-PLF antibody to mice reduced BrdU incorporation into adipocytes. Mature adipocytes thus have the ability to replicate, and this proliferation is positively regulated by PLF

Comparison of Pentax-AWS Airwayscope and Glidescope for Infant Tracheal Intubation by Anesthesiologists during Cardiopulmonary Arrest Simulation: A Randomized Crossover Trial

Background. Recent guidelines for infant cardiopulmonary resuscitation emphasize that all rescuers should minimize interruption of chest compressions, even for endotracheal intubation. We compared the utility of the Pentax-AWS Airwayscope (AWS) with the Glidescope (GS) during chest compressions on an infant manikin. Methods. Twenty-four anesthesiologists with more than two years of experience performed tracheal intubation on an infant manikin using the AWS and GS, with or without chest compressions. Results. In GS trials, none of the participants failed without compressions, while three failed with compressions. In AWS trials, all participants succeeded regardless of chest compressions. Intubation time was significantly longer with chest compressions with the GS ( < 0.05), but not with the AWS. Difficulty of operation on a visual analog scale (VAS) for laryngoscopy did not increase significantly with chest compressions with either the GS or the AWS, while the VAS for tube passage through the glottis increased with compressions with the GS, but not with the AWS. Conclusion. We conclude that in infant simulations managed by anesthesiologists, the AWS performed better than the GS for endotracheal intubation with chest compressions

Osimertinib Did Not Respond to a Pulmonary Adenocarcinoma with Triple Mutations of Epidermal Growth Factor Receptor, G719S, T790M and S768I

Uncommon epidermal growth factor receptor (EGFR) gene mutations include G719S, T790M and S768I. T790M gatekeeper mutation is the most frequent mechanism of acquired drug resistance to first- and second-generation EGFR-tyrosine kinase inhibitors (TKIs). Osimertinib is a specific EGFR-TKI to overcome T790M resistance mutation. However, owing to a new drug and a rare mutation type, it remains unknown whether osimertinib is effective for acquired S768I. Herein, we reported a 76 year-old woman with pulmonary adenocarcinoma, which had acquired EGFR mutations of S768I and T790M in addition to original G719S after long gefitinib treatment. These mutations were detected in biopsy specimen of liver metastases. During two months of osimertinib, multiple liver metastases progressively enlarged. This case suggested that acquired S768I mutation might be resistant to osimeritinib, despite of co-occurrence of T790M

Preconditioning of primary human endothelial cells with inflammatory mediators alters the “set point” of the cell

Endothelial cells are highly sensitive to changes in the extracellular milieu. Sepsis results in activation of inflammatory and coagulation pathways. We hypothesized that sepsis-associated mediators may alter the response capacity (so-called “set point”) of endothelial cells. Human umbilical vein endothelial cells (HUVEC) were preincubated in the presence or absence of tumor necrosis factor (TNF)-α, lipopolysaccharide (LPS), hypoxia, hyperthermia, and/or high glucose; treated with or without thrombin for 4 h; and then processed for RNase protection assays of selected activation markers. Priming with TNF-α and LPS significantly inhibited thrombin-mediated induction of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, tissue factor, and E-selectin, but not platelet-derived growth factor-A or CD44. In electrophoretic mobility shift assays, thrombin-treated HUVEC demonstrated inducible binding of p65 NF-κB, an effect that was significantly blunted by pretreatment of cells with TNF-α and LPS. Consistent with these results, TNF-α and LPS attenuated the effect of thrombin on IκB phosphorylation, total cytoplasmic IκB, and nuclear translocation of p65 NF-κB. The inhibitory effect of TNF-α on thrombin signaling persisted for up to 24 h following removal of the cytokine. Taken together, these data suggest that inflammatory mediators prime endothelial cells to modulate subsequent thrombin response

Density fluctuation measurements using beam emission spectroscopy on Heliotron J

Contributed paper, published as part of the Proceedings of the 19th Topical Conference on High Temperature Plasma Diagnostics, Monterey, California, May 2012.This paper describes the measurement of the density fluctuation using beamemission spectroscopy in Heliotron J, having the non-symmetrical helical-magnetic-axis configuration. In order to optimize the sightlines, the numerical calculations are carried out to estimate the spatial resolution and the observation location. When a tangential neutral beam is used as diagnostic one, suitable sightlines from the newly installed diagnostic port are selected whose spatial resolution Δρ is less than ±0.07 over the entire plasma region. Modification of the interference filter and the detection systems enables us to measure the radial profile of the density fluctuation. Each of the three coherent modes due to the fast-ion-driven magnetohydrodynamic instabilities has different radial structure of the density fluctuation

Analysis of Serum Fatty Acids and Vitamin D with Dimension Reduction Methods

Fatty acid plays an important role in human health and fat-related diseases. A comprehensive analysis of diverse fatty acids in serum naturally results in a multi-variable, high-dimensional dataset, and, therefore, multivariate analysis, especially dimension reduction, should be considered to extract useful information. In this study, three basic dimension reduction methods including factor analysis, principal component analysis, and independent component analysis were conducted on total and free fatty acid datasets in a general Japanese population (N=545; men:women=245:300). These analyses successfully characterized fatty acid datasets, reflecting their physicochemical natures, metabolisms, and food sources. Factor analysis and principal component demonstrated the association of -3 fatty acids (20:5 and 22:6) with 25-hydroxyvitamin D3 (vitamin D), suggesting fish oil as their common source of vitamin D. We conclude that dimension reductions can serve as a useful tool to extract valuable information from complex datasets of fatty acids and vitamin D in the aspect of health care and disease control

Activation of Cdc42 by trans interactions of the cell adhesion molecules nectins through c-Src and Cdc42-GEF FRG

Nectins, Ca2+-independent immunoglobulin-like cell–cell adhesion molecules, initiate cell–cell adhesion by their trans interactions and recruit cadherins to cooperatively form adherens junctions (AJs). In addition, the trans interactions of nectins induce the activation of Cdc42 and Rac small G proteins, which increases the velocity of the formation of AJs. We examined here how nectins induce the activation of Cdc42 in MDCK epithelial cells and L fibroblasts. Nectins recruited and activated c-Src at the nectin-based cell–cell adhesion sites. FRG, a GDP/GTP exchange factor specific for Cdc42, was then recruited there, tyrosine phosphorylated by c-Src, and activated, causing an increase in the GTP-bound active form of Cdc42. Inhibition of the nectin-induced activation of c-Src suppressed the nectin-induced activation of FRG and Cdc42. Inhibition of the nectin-induced activation of FRG or depletion of FRG by RNA interference suppressed the nectin-induced activation of Cdc42. These results indicate that nectins induce the activation of Cdc42 through c-Src and FRG locally at the nectin-based cell–cell adhesion sites

Impact of extracellular matrix on engraftment and maturation of pluripotent stem cell-derived cardiomyocytes in a rat myocardial infarct model

Pluripotent stem cell-derived cardiomyocytes show great promise in regenerating the heart after myocardial infarction; however, several uncertainties exist that must be addressed before clinical trials. One practical issue is graft survival following transplantation. Although a pro-survival cocktail with Matrigel has been shown to enhance graft survival, the use of Matrigel may not be clinically feasible. The purpose of this study was to test whether a hyaluronan-based hydrogel, HyStem, could be a substitute for Matrigel. Human induced pluripotent stem cell-derived cardiomyocytes diluted with HyStem alone, HyStem plus pro-survival factors, or a pro-survival cocktail with Matrigel (PSC/MG), were transplanted into a rat model of acute myocardial infarction. Histological analysis at 4 weeks post transplantation revealed that, among the three groups, recipients of PSC/MG showed the largest graft size. Additionally, the grafted cardiomyocytes in the recipients of PSC/MG had a more matured phenotype compared to those in the other two groups. These findings suggest that further studies will be required to enhance not only graft size, but also the maturation of grafted cardiomyocytes.ArticleScientific reports 7(1) : 8630-(2017)journal articl