CT and MRI Findings of Low-Flow Mediastinal Vascular Malformation: A Case Report.

Mediastinal vascular malformations are rare and their diagnosis can be challenging. Imaging is vital for diagnosing mediastinal vascular malformations and can help avoid unnecessary invasive procedures. Herein, we report the detailed CT and MRI findings of a rare low-flow mediastinal vascular malformation in an asymptomatic 63-year-old male.

Evaluation of factors influencing survival time in 77 dogs with lymphoma.

Background: Canine lymphoma is one of the most commonly reported hematopoietic tumors. Aim: A few retrospective studies have involved complex evaluations including diagnostic features and treatment protocols, but these studies infrequently demonstrate variable factors that affect survival time, and comparisons among chemotherapeutic protocols are limited. This study aimed to identify prognostic factors that can be simply detected in dogs with lymphoma, such as abnormalities in physical and hematologic findings, and treatment protocols. Methods: Clinical records of 77 dogs diagnosed with lymphoma were retrospectively reviewed. Results: The author newly identified leukocyte and platelet abnormalities as negative prognostic factors. Furthermore, this study suggests that decreased gastrointestinal toxicity and improvements of hematologic abnormalities, such as anemia, thrombocytopenia, and lymphocytosis or lymphoblasts, in peripheral blood during chemotherapy act as positive prognostic factors. Finally, strict adherence to therapeutic protocol and selecting multiple agents as rescue protocol are important to prolong survival time. Conclusion: This study identified indicators to be used as prognostic factors through survival analysis.

Real-time monitoring of oncolytic VSV properties in a novel in vitro microphysiological system containing 3D multicellular tumor spheroids.

As a new class of cancer therapeutic agents, oncolytic viruses (OVs) have gained much attention not only due to their ability to selectively replicate in and lyse tumor cells, but also for their potential to stimulate antitumor immune responses. As a result, there is an increasing need for in vitro modeling systems capable of recapitulating the 3D physiological tumor microenvironment. Here, we investigated the potential of our recently developed microphysiological system (MPS), featuring a vessel-like channel to reflect the in vivo tumor microenvironment and serving as culture spaces for 3D multicellular tumor spheroids (MCTSs). The MCTSs consist of cancer A549 cells, stromal MRC5 cells, endothelial HUVECs, as well as the extracellular matrix. 3D MCTSs residing in the MPS were infected with oncolytic VSV expressing GFP (oVSV-GFP). Post-infection, GFP signal intensity increased only in A549 cells of the MPS. On the other hand, HUVECs were susceptible to virus infection under 2D culture and IFN-ß secretion was quite delayed in HUVECs. These results thus demonstrate that OV antitumoral characteristics can be readily monitored in the MPS and that its behavior therein somewhat differs compared to its activity in 2D system. In conclusion, we present the first application of the MPS, an in vitro model that was developed to better reflect in vivo conditions. Its various advantages suggest the 3D MCTS-integrated MPS can serve as a first line monitoring system to validate oncolytic virus efficacy.

Diagnostic performance of dual-energy computed tomography for detection of acute spinal fractures.

OBJECTIVE: To assess the diagnostic performance of dual-energy computed tomography (DECT) with the color-coded virtual non-calcium (VNC) technique for detecting acute fractures in patients after acute spine trauma, especially in an emergency clinical setting. MATERIALS AND METHODS: Our retrospective study included 31 patients presented to emergency department with suspected spine trauma. All patients underwent both DECT (80 kVp and 140 kVp) and MRI. Post-processing was performed using color-coded VNC technique. Two independent radiologists visually assessed color-coded VNC images in a random order, and one of the two readers re-assessed the images in 4 weeks after the initial assessment. They were allowed to read only color-coded VNC images and asked to determine the presence of acute fracture. To determine the standard reference point, the other two experienced radiologists made consensus readings on both grayscale CT and MRI. Sensitivity, specificity, PPV, NPV, and accuracy analyses were determined. Both intra- and inter-observer agreements were also calculated. RESULTS: A total of 217 vertebral bodies (65 thoracic and 152 lumbar vertebrae) were included in our study. Sensitivity was 83.3% and 76.7% for first and second readers, respectively. Specificity of 99.5% and 98.9%, PPV of 96.1% and 96.3%, NPV of 97.3% and 96.3%, and accuracy of 97.2% and 95.8%, respectively, were noted. Both intra-observer and inter-observer agreements indicated excellent agreement (κ = 0.86 and κ = 0.84, respectively). CONCLUSION: In spite of the relatively low sensitivity, DECT-based detection of acute spinal fractures showed good specificity, positive predictive value, negative predictive value, accuracy, and inter-/intra-observer agreements.

Evaluation of Bystander Infection of Oncolytic Virus using a Medium Flow Integrated 3D In Vitro Microphysiological System.

Replicable oncolytic viruses (OVs) induce tumor cell lysis and release viral progeny. The released progeny virions and cell debris can spread within surrounding tumor cells or blood vessels. These released molecules may also induce bystander damage in additional tumor cells through spreading within surrounding tumor cells or blood vessels. However, this effect has not been clearly demonstrated due to the difficulty of direct observation. Here, the bystander infection of OVs by vessel delivery and selective infection in 3D multicellular tumoroids (MCTs) in an in vitro microphysiological system (MPS) with integrated medium flow is demonstrated. This study uses replicable vesicular stomatitis virus (VSV)-green fluorescence protein (GFP) to identify the location of infection in 3D MCTs. Using this MPS, the oncoselective infection by VSV-GFP and the spreading by delivery of OVs through flow via block-to-block linkage of the primary infected MPS with uninfected 3D MCTs in an integrated MPS is observed. This MPS enables real-time monitoring and various analysis for the bystander infection of OVs. It is expected that the 3D in vitro MPS can be suitable to investigate the oncoselective spreading and bystander infection of OVs.

Crystal structure of L-aspartate aminotransferase from Schizosaccharomyces pombe.

L-aspartate aminotransferase is a pyridoxal 5'-phosphate-dependent transaminase that catalyzes reversible transfer of an α-amino group from aspartate to α-ketoglutarate or from glutamate to oxaloacetate. L-aspartate aminotransferase not only mediates amino acid and carbohydrate metabolism but also regulates the cellular level of amino acids by catalyzing amino acid degradation and biosynthesis. To expand our structural information, we determined the crystal structure of L-aspartate aminotransferase from Schizosaccharomyces pombe at 2.1 Å resolution. A structural comparison between two yeast L-aspartate aminotransferases revealed conserved enzymatic mechanism mediated by the open-closed conformational change. Compared with higher eukaryotic species, L-aspartate aminotransferases showed distinguishable inter-subunit interaction between the N-terminal arm and a large domain of the opposite subunit. Interestingly, structural homology search showed varied conformation of the N-terminal arm among 71 structures of the family. Therefore, we classified pyridoxal 5'-phosphate-dependent enzymes into eight subclasses based on the structural feature of N-terminal arms. In addition, structure and sequence comparisons showed strong relationships among the eight subclasses. Our results may provide insights into structure-based evolutionary aspects of pyridoxal 5'-phosphate-dependent enzymes.

In vitro lung cancer multicellular tumor spheroid formation using a microfluidic device.

The purpose of this study was to demonstrate self-organizing in vitro multicellular tumor spheroid (MCTS) formation in a microfluidic system and to observe the behavior of MCTSs under controlled microenvironment. The employed microfluidic system was designed for simple and effective formation of MCTSs by generating nutrient and oxygen gradients. The MCTSs were composed of cancer cells, vascular endothelial cells, and type I collagen matrix to mimic the in vivo tumor microenvironment (TME). Cell culture medium was perfused to the microfluidic device loaded with MCTSs by a passive fluidic pump at a constant flow rate. The dose response to an MMPs inhibitor was investigated to demonstrate the effects of biochemical substances. The result of long-term stability of MCTSs revealed that continuous perfusion of cell culture medium is one of the major factors for the successful MCTS formation. A continuous flow of cell culture medium in the in vitro TME greatly affected both the proliferation of cancer cells in the micro-wells and the sustainability of the endothelial cell-layer integrity in the lumen of microfluidic channels. Addition of MMP inhibitor to the cell culture medium improved the stability of the collagen matrix by preventing the detachment and shrinkage of the collagen matrix surrounding the MCTSs. In summary, the present constant flow assisted microfluidic system is highly advantageous for long-term observation of the MCTS generation, tumorous tissue formation process and drug responses. MCTS formation in a microfluidic system may serve as a potent tool for studying drug screening, tumorigenesis and metastasis.

A cell-loss-free concave microwell array based size-controlled multi-cellular tumoroid generation for anti-cancer drug screening.

The 3D multi-cellular tumoroid (MCT) model is an in vivo-like, avascular tumor model that has received much attention as a refined screening platform for drug therapies. Several types of research have been efforted to improve the physiological characteristics of the tumor microenvironment (TME) of the in vivo-like MCTs. Size-controlled MCTs have received much attention for obtaining highly reproducible results in drug screening assays and achieving a homogeneous and meaningful level of biological activities. Here, we describe an effective method for fabricating the size-controlled in vivo-like MCTs using a cell-loss-free (CLF) microwell arrays. The CLF microwell arrays was fabricated by using the simple operation of laser carving of a poly (methyl methacrylate) (PMMA) master mold. We also demonstrated the biophysicochemical effect of tumor microenvironment (TME) resident fibroblasts through the expression of TGFß, αSMA, Type I-, IV collagen, angiogenesis related markers on tumorigenesis, and confirmed the drug response of MCTs with anti-cancer agents. This technology for the fabrication of CLF microwell arrays could be used as an effective method to produce an in vitro tumor model for cancer research and drug discovery.

Effect of 222-nm krypton-chloride excilamp treatment on inactivation of Escherichia coli O157:H7 and Salmonella Typhimurium on alfalfa seeds and seed germination.

We examined the control effect of a 222-nm KrCl excilamp on foodborne pathogens on alfalfa seeds and compared it with a conventional 254-nm low-pressure (LP) Hg lamp. When the 222-nm KrCl excilamp treated seeds at 87, 174 and 261 mJ/cm2, the log reductions of Escherichia coli O157:H7 (E. coli O157:H7) were 0.85, 1.77, and 2.77, respectively, and Salmonella Typhimurium (S. Typhimurium) experienced log reductions of 1.22, 2.27, and 3.04, respectively. When the 254-nm LP Hg lamp was applied at 87, 174, and 261 mJ/cm2, the log reductions of E. coli O157: H7 were 0.7, 1.16, and 1.43, respectively, and those of S. Typhimurium were 0.75, 1.15, and 1.85, respectively. Therefore, it was shown that the 222-nm KrCl excilamp was more effective than the 254-nm LP Hg lamp in reducing foodborne pathogens. The germination rate decreased to less than 80% after 261 mJ/cm2 treatment with the 254-nm LP Hg lamp, while more than 90% was maintained with 261 mJ/cm2 222-nm KrCl excilamp treatment. DNA damage assay showed that the difference in germination rate was due to DNA damage resulting from 254-nm LP Hg lamp treatment. However, 222 nm KrCl excilamp treatment did not cause DNA damage, resulting in no difference in germination rate compared to that of non-treated alfalfa seeds. Overall, these results demonstrate the utility of the 222-nm KrCl excilamp as a foodborne pathogen control intervention for the alfalfa seed industry.

l-Glutamine Attenuates DSS-Induced Colitis via Induction of MAPK Phosphatase-1.

Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn's disease, is a multifactorial inflammatory disease of the small intestine and colon. Many investigators have reported that l-glutamine (Gln) therapy improves outcomes of experimental colitis models, although the mechanism is not fully understood. Regarding the anti-inflammatory properties of Gln, we have shown that Gln can effectively deactivate cytosolic phospholipase A2 (cPLA2) by rapid induction of MAPK phosphatase (MKP)-1. In this study, we explore the possibility that Gln ameliorates dextran sulfate sodium (DSS)-induced colitis via MKP-1 induction, resulting in inhibition of cPLA2, which has been reported to play a key role in the pathogenesis of IBD. Oral Gln intake attenuated DSS-induced colitis. Gln inhibited cPLA2 phosphorylation, as well as colonic levels of TNF-α and leukotriene (LT)B4. Gln administration resulted in early and enhanced MKP-1 induction. Importantly, MKP-1 small interfering RNA (siRNA), but not control siRNA, significantly abrogated the Gln-mediated (1) induction of MKP-1; (2) attenuation of colitis (colon length, histological abnormality, and inflammation; and (3) inhibition of cPLA2 phosphorylation and colonic levels of TNF-α and LTB4. These data indicated that Gln ameliorated DSS-induced colitis via MKP-1 induction.

The effects of bilateral subthalamic nucleus deep brain stimulation (STN DBS) on cognition in Parkinson disease.

The effects of subthalamic nucleus (STN) stimulation on cognition and mood have not been well established. The authors estimated cognitive and mood effects of bilateral subthalamic nucleus deep brain stimulation (STN DBS) in patients with Parkinson's disease (PD) at 6 months and 1 year postoperatively. Forty-six patients were recruited from the Movement Disorder Center at Seoul National University Hospital. Neuropsychologic tests were performed three times, before, 6 months after, and 1 year after surgery. Mean patient age was 58 and mean education duration 8 years. Eighteen of the 46 patients were men. The instruments used for assessing cognitive functions were; the Mini-Mental Status Examination (MMSE), the Trail Making Test (TMT), the Korean Boston Naming Test (K-BNT), the Rey-Kim Memory Battery, the Grooved pegboard test, the Stroop test, a fluency test, the Wisconsin Card Sorting test (WCST), and the Beck depression inventory (BDI). Of these tests, the verbal memory test, the Stroop test, and the fluency test showed statistically significant changes. The verbal memory test using the Rey-Kim memory battery showed a decline in delayed recall and recognition at 6 months and 1 year postoperatively, whereas nonverbal memory showed no meaningful change. In terms of frontal lobe function tests, Stroop test and fluency test findings were found to be aggravated at 6 months and this continued at 1 year postoperatively. Previous studies have consistently reported a reduction in verbal fluency and improvements in self-reported symptoms of depression after STN DBS. However, in the present study, Beck depression inventory (B.D.I.) was not significantly changed. Other tests, namely, MMSE, TMT, K-BNT, Grooved pegboard test, and the WCST also failed to show significant changes. Of the baseline characteristics, age at onset, number of years in full-time education, and L-dopa equivalent dosage were found to be correlated with a postoperative decline in neuropsychological test results. The correlation of motor improvement and cognitive deterioration was not significant, which suggests that the stimulation effect is rather confined to the motor-related part in the STN. In conclusion, bilateral STN DBS in Parkinson's disease did not lead to a significant global deterioration in cognitive function. However, our findings suggest that it has minor detrimental long-term impacts on memory and frontal lobe function.