Comparison of the Plasma Metabolome Profiles Between the Internal Thoracic Artery and Ascending Aorta in Patients Undergoing Coronary Artery Bypass Graft Surgery Using Gas Chromatography Time-of-Flight Mass Spectrometry.

BackgroundThe left internal thoracic artery (LITA) has been used as the first conduit of choice in coronary artery bypass grafting (CABG) because of excellent long-term patency and outcomes. However, no studies have examined substances other than nitric oxide that could be beneficial for the bypass conduit, native coronary artery or ischemic myocardium. This study was conducted to evaluate differences in metabolic profiles between the LITA and ascending aorta using gas chromatography-time of flight-mass spectrometry (GC-TOF-MS).MethodsTwenty patients who underwent CABG using the LITA were prospectively enrolled. Plasma samples were collected simultaneously from the LITA and ascending aorta. GC-TOF-MS based untargeted metabolomic analyses were performed and a 2-step volcano plot analysis was used to identify distinguishable markers from two plasma metabolome profiles. Semi-quantitative and quantitative analyses were performed using GC-TOF-MS and enzyme-linked immunosorbent assay, respectively, after selecting target metabolites based on the metabolite set enrichment analysis.ResultsInitial volcano plot analysis demonstrated 5 possible markers among 851 peaks detected. The final analysis demonstrated that the L-cysteine peak was significantly higher in the LITA than in the ascending aorta (fold change = 1.86). The concentrations of intermediate metabolites such as L-cysteine, L-methionine and L-cystine in the 'cysteine and methionine metabolism pathway' were significantly higher in the LITA than in the ascending aorta (2.0-, 1.4- and 1.2-fold, respectively). Quantitative analysis showed that the concentration of hydrogen sulfide (H₂S) was significantly higher in the LITA.ConclusionThe plasma metabolome profiles of the LITA and ascending aorta were different, particularly higher plasma concentrations of L-cysteine and H₂S in the LITA

Investigation of the transverse beam dynamics in the thermal wave model with a functional method

We investigated the transverse beam dynamics in a thermal wave model by using a functional method. It can describe the beam optical elements separately with a kernel for a component. The method can be applied to general quadrupole magnets beyond a thin lens approximation as well as drift spaces. We found that the model can successfully describe the PARMILA simulation result through an FODO lattice structure for the Gaussian input beam without space charge effects.Comment: 12 pages, 6 figure

Trajectory Generation for Assembly Tasks Via Bilateral Teleoperation

Abstract in UndeterminedFor assembly tasks, the knowledge of both trajectory and forces are usually required. Consequently, we may use kinesthetics or teleoperation for recording human demonstrations. In order to have a more natural interaction, the operator has to be provided with a sense of touch. We propose a bilateral teleoperation system which is customized for this purpose. We introduce different coordinate frames to make the design of a 6-DOF teleoperation straightforward. Moreover, we suggest using tele-admittance, which simplifies instructing the robot. The compliance due to the slave controller allows the robot to react quickly and reduces the risk of damaging the workpiece

Evaluation of the usefulness of three-dimensional optical coherence tomography in a guinea pig model of endolymphatic hydrops induced by surgical obliteration of the endolymphatic duct

Optical coherence tomography (OCT) has advanced significantly over the past two decades and is currently used extensively to monitor the internal structures of organs, particularly in ophthalmology and dermatology. We used ethylenediamine tetra-acetic acid (EDTA) to decalcify the bony walls of the cochlea and investigated the inner structures by deep penetration of light into the cochlear tissue using OCT on a guinea pig model of endolymphatic hydrops (EH), induced by surgical obliteration of the endolymphatic duct. The structural and functional changes associated with EH were identified using OCT and auditory brainstem response tests, respectively. We also evaluated structural alterations in the cochlea using three-dimensional reconstruction of the OCT images, which clearly showed physical changes in the cochlear structures. Furthermore, we found significant anatomical variations in the EH model and conducted graphical analysis by strial atrophy for comparison. The physical changes included damage to and flattening of the organ of Corti-evidence of Reissner's membrane distention-and thinning of the lateral wall. These results indicate that observation of EDTA-decalcified cochlea using OCT is significant in examination of gradual changes in the cochlear structures that are otherwise not depicted by hematoxylin and eosin staining © The Authorsopen0

Anti-programmed death ligand 1 (PD-L1) inhibitors in metastatic gastric cancer

Metastatic gastric cancer (GC) with limited therapeutic options has a poor prognosis, and therefore, major therapeutic advances are needed. Comprehensive genomic characterization has improved understanding of GC but a great majority of genomic profiling has not been effectively translated to the clinical benefit yet. The introduction of immunotherapy with anti-programmed death ligand 1 (PD-L1) antibody such as pembrolizumab or nivolumab resulted in a rapid paradigm shift in the field of medical oncology and their clinical indication has been expanding in the past few years. Now, the era of immunotherapy in metastatic GC has arrived with recent trial results in survival benefit from anti-PD-L1 antibody. Herein, we review the mechanisms of immunotherapy, clinical trials that have been conducted or are in progress, and the potential for PD-L1 as a predictive biomarker for GC

Fate of Sudden Deafness Occurring in the Only Hearing Ear: Outcomes and Timing to Consider Cochlear Implantation

The present study was undertaken to learn the outcome of patients with idiopathic sudden sensorineural hearing loss (ISSNHL) in their only hearing ear. Timing to conduct a cochlear implantation was also determined in those who did not recover the hearing. The study group comprised 25 patients who confronted ISSNHL in their only hearing ear. A total of 192 patients, who had ISSNHL in one ear and had normal contralateral ear, served as the control. Demographically there were no significant differences between the groups. The recovery rate was similar between the groups: 64.0% in the experimental and 62.5% in the control group. The duration until the recovery of ISSNHL in the only hearing ear was 5-90 days (average 17.6 days). In the experimental group, 8 patients did not recover from ISSNHL, and underwent cochlear implantation in 6 with satisfactory results. These results suggest that the same treatment is applicable for patients with ISSNHL regardless of whether their contralateral ear is deaf or normal. For those who do not recover from ISSNHL in their only hearing ear, culminating in bilateral deafness, we may consider further definitive treatment including cochlear implantation as early as 3 months after initiating the treatment of ISSNHL

Fate of Sudden Deafness Occurring in the Only Hearing Ear: Outcomes and Timing to Consider Cochlear Implantation

The present study was undertaken to learn the outcome of patients with idiopathic sudden sensorineural hearing loss (ISSNHL) in their only hearing ear. Timing to conduct a cochlear implantation was also determined in those who did not recover the hearing. The study group comprised 25 patients who confronted ISSNHL in their only hearing ear. A total of 192 patients, who had ISSNHL in one ear and had normal contralateral ear, served as the control. Demographically there were no significant differences between the groups. The recovery rate was similar between the groups: 64.0% in the experimental and 62.5% in the control group. The duration until the recovery of ISSNHL in the only hearing ear was 5-90 days (average 17.6 days). In the experimental group, 8 patients did not recover from ISSNHL, and underwent cochlear implantation in 6 with satisfactory results. These results suggest that the same treatment is applicable for patients with ISSNHL regardless of whether their contralateral ear is deaf or normal. For those who do not recover from ISSNHL in their only hearing ear, culminating in bilateral deafness, we may consider further definitive treatment including cochlear implantation as early as 3 months after initiating the treatment of ISSNHL

Functional neural differentiation of human adipose tissue-derived stem cells using bFGF and forskolin

<p>Abstract</p> <p>Background</p> <p>Adult mesenchymal stem cells (MSCs) derived from adipose tissue have the capacity to differentiate into mesenchymal as well as endodermal and ectodermal cell lineage <it>in vitro</it>. We characterized the multipotent ability of human adipose tissue-derived stem cells (hADSCs) as MSCs and investigated the neural differentiation potential of these cells.</p> <p>Results</p> <p>Human ADSCs from earlobe fat maintained self-renewing capacity and differentiated into adipocytes, osteoblasts, or chondrocytes under specific culture conditions. Following neural induction with bFGF and forskolin, hADSCs were differentiated into various types of neural cells including neurons and glia <it>in vitro</it>. In neural differentiated-hADSCs (NI-hADSCs), the immunoreactivities for neural stem cell marker (nestin), neuronal markers (Tuj1, MAP2, NFL, NFM, NFH, NSE, and NeuN), astrocyte marker (GFAP), and oligodendrocyte marker (CNPase) were significantly increased than in the primary hADSCs. RT-PCR analysis demonstrated that the mRNA levels encoding for ABCG2, nestin, Tuj1, MAP2, NFL, NFM, NSE, GAP43, SNAP25, GFAP, and CNPase were also highly increased in NI-hADSCs. Moreover, NI-hADSCs acquired neuron-like functions characterized by the display of voltage-dependent tetrodotoxin (TTX)-sensitive sodium currents, outward potassium currents, and prominent negative resting membrane potentials under whole-cell patch clamp recordings. Further examination by RT-PCR showed that NI-hADSCs expressed high level of ionic channel genes for sodium (SCN5A), potassium (MaxiK, Kv4.2, and EAG2), and calcium channels (CACNA1C and CACNA1G), which were expressed constitutively in the primary hADSCs. In addition, we demonstrated that Kv4.3 and Eag1, potassium channel genes, and NE-Na, a TTX-sensitive sodium channel gene, were highly induced following neural differentiation.</p> <p>Conclusions</p> <p>These combined results indicate that hADSCs have the same self-renewing capacity and multipotency as stem cells, and can be differentiated into functional neurons using bFGF and forskolin.</p

Mesenchymal Stem Cells Improve Wound Healing In Vivo via Early Activation of Matrix Metalloproteinase-9 and Vascular Endothelial Growth Factor

We investigated the effects of mesenchymal stem cells (MSCs) on wound healing using a three-dimensional (3D) collagen gel scaffold. Three circular full-thickness skin defects were created on the back of Sprague-Dawley rats. One site was covered with a 3D collagen gel containing 2 × 106 MSCs (MSCs+/3D collagen+). Another site was replaced with a 3D collagen gel without MSCs and the third site was left empty. The wound size was significantly reduced in the MSCs+/3D collagen+ sites. MSCs+/3D collagen+ sites exhibited the most neovascularization. FISH showed that Y-chromosome possessing cells were found within the dermis of MSCs+/3D collagen+ sites. Gelatin zymography revealed that the most intense expression of MMP-9 was detected early in the MSCs+/3D collagen+ sites. Our results indicate that MSCs upregulate the early expression of MMP-9 which induces the early mobilization of VEGF. Thus, MSCs appear to accelerate significantly wound healing via early activation of MMP-9 and VEGF