Radiative Transfer in Ly{\alpha} Nebulae: I. Modeling a Continuous or Clumpy Spherical Halo with a Central Source

To understand the mechanism behind high-$z$ Ly${\alpha}$ nebulae, we simulate the scattering of Ly${\alpha}$ in a $\rm H\,I$ halo about a central Ly${\alpha}$ source. For the first time, we consider both smooth and clumpy distributions of halo gas, as well as a range of outflow speeds, total $\rm H\,I$ column densities, $\rm H\,I$ spatial concentrations, and central source galaxies (e.g., with Ly${\alpha}$ line widths corresponding to those typical of AGN or star-forming galaxies). We compute the spatial-frequency diffusion and the polarization of the Ly${\alpha}$ photons scattered by atomic hydrogen. Our scattering-only model reproduces the typical size of Ly${\alpha}$ nebulae ($\sim 100\,$kpc) at total column densities $N_{\rm HI} \geq 10^{20} \rm cm^{-2}$ and predicts a range of positive, flat, and negative polarization radial gradients. We also find two general classes of Ly${\alpha}$ nebula morphologies: with and without bright cores. Cores are seen when $N_{\rm HI}$ is low, i.e., when the central source is directly visible, and are associated with a polarization jump, a steep increase in the polarization radial profile just outside the halo center. Of all the parameters tested in our smooth or clumpy medium model, $N_{\rm HI}$ dominates the trends. The radial behaviors of the Ly${\alpha}$ surface brightness, spectral line shape, and polarization in the clumpy model with covering factor $f_c \gtrsim 5$ approach those of the smooth model at the same $N_{\rm HI}$. A clumpy medium with high $N_{\rm HI}$ and low $f_c \lesssim 2$ generates Ly${\alpha}$ features via scattering that the smooth model cannot: a bright core, symmetric line profile, and polarization jump.Comment: 42 pages, 27 figures, accepted for publication in ApJ, Comments welcome

RS3PE syndrome with subsequent PMR caused by long-term DPP-4 inhibitor use

Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome has been reported in patients treated with dipeptidyl peptidase-4 inhibitors (DPP-4i). We experienced a case of RS3PE syndrome in a 73-year-old man with a history of type 2 diabetes, who developed RS3PE as a side effect of vildagliptin. Further to this, the patient developed polymyalgia rheumatica (PMR), the first such case associated with long-term DPP-4i use

NF- κ

AP736 was identified as an antimelanogenic drug that can be used for the prevention of melasma, freckles, and dark spots in skin by acting as a suppressor of melanin synthesis and tyrosinase expression. Since macrophage-mediated inflammatory responses are critical for skin health, here we investigated the potential anti-inflammatory activity of AP736. The effects of AP736 on various inflammatory events such as nitric oxide (NO)/prostaglandin (PG) E2 production, inflammatory gene expression, phagocytic uptake, and morphological changes were examined in RAW264.7 cells. AP736 was found to strongly inhibit the production of both NO and PGE2 in lipopolysaccharide- (LPS-) treated RAW264.7 cells. In addition, AP736 strongly inhibited both LPS-induced morphological changes and FITC-dextran-induced phagocytic uptake. Furthermore, AP736 also downregulated the expression of multiple inflammatory genes, such as inducible NO synthase (iNOS), cyclooxygenase- (COX-) 2, and interleukin- (IL-) 1β in LPS-treated RAW264.7 cells. Transcription factor analysis, including upstream signalling events, revealed that both NF-κB and AP-1 were targeted by AP736 via inhibition of the IKK/IκBα and IRAK1/TAK1 pathways. Therefore, our results strongly suggest that AP736 is a potential anti-inflammatory drug due to its suppression of NF-κB-IKK/IκBα and AP-1-IRAK1/TAK1 signalling, which may make AP736 useful for the treatment of macrophage-mediated skin inflammation

A clinical predictor of varices and portal hypertensive gastropathy in patients with chronic liver disease

Background/AimsThe aim of this study was to identify the parameters that could noninvasively predict the presence of esophageal/gastric varices and portal hypertensive gastropathy (PHG) in patients with chronic liver disease (CLD), and to determine the accuracy of those parameters.MethodsWe retrospectively analyzed 232 patients with CLD who underwent both upper endoscopy and liver CT within an interval of 3 months. The multidimensional index (M-Index) for spleen volume was obtained from the multiplication of splenic length, width, and thickness, as measured by computer tomography.ResultsThe multivariate analysis revealed that platelet, albumin, and M-Index were independently associated with the presence of varices and PHG. We combined three independent parameters, and developed a varices and portal hypertensive gastropathy (VAP) scoring system (=[platelet count (/mm3)×albumin (g/dL)]/[M-Index (cm3)]). The area under the receiver operating characteristic curve of the VAP score was 0.850 (95% confidence interval, 0.801-0.899). The VAP cut-off value of 861 had a sensitivity of 85.3%, a positive likelihood ratio of 3.17, and a negative predictive value of 86.4%. For predicting high-risk lesions for bleeding, with a cut-off value of 861 the sensitivity was 92.0%, the positive likelihood ratio was 2.20, and the negative predictive value was 96.4%.ConclusionsThe VAP score can predict the presence of varices and PHG in patients with CLD and may increase the cost-benefit of screening endoscopy in the clinical practice setting. A prospective validation study is necessary in the future

Sound Analysis in an In Vitro Endotracheal Tube Model

Background/Aims: Complete endotracheal tube obstruction is a medical emergency, and partial occlusion causes increased breathing rates and failure to wean off mechanical ventilation. Partial occlusion may be underestimated due to the lack of proper detection methods. We tested whether the sound of an endotracheal tube could be used to detect an endotracheal tube obstruction using an in vitro model. Methods: An endotracheal tube was connected to a ventilator on one end and a test lung on the other. Sounds were recorded with a microphone located inside the endotracheal tube via a connector. During mechanical ventilation, we changed the endotracheal tube internal diameter from 5.0 to 8.0 mm and different grades of obstruction at different sites were used along the tube. Sound energy was compared among the different conditions. Results: The energy of endotracheal tube sounds was positively correlated with the internal diameter and negatively correlated with the degree of obstruction. The rate of decline in energy differed with obstruction location. When the obstruction was more distal, the rate of decline in endotracheal sound energy was more rapid. Conclusions: Changes in the sound of an endotracheal tube can be used to detect an obstruction. Further studies are needed for clinical application. © 2011 The Korean Association of Internal Medicine.Y

Detection of Sentinel Lymph Nodes in patients with Early Stage Cervical Cancer

The purpose of this study was to determine the feasibility of identifying the sentinel lymph nodes (SNs) as well as to evaluate factors that might influence the SN detection rate in patients with cervical cancer of the uterus. Eighty nine patients underwent intracervical injection of 1% isosulfan blue dye at the time of planned radical hysterectomy and lymphadenectomy between January 2003 and December 2003. With the visual detection of lymph nodes that stained blue, SNs were identified and removed separately. Then all patients underwent complete pelvic lymph node dissection and/or para-aortic lymph node dissection. SNs were identified in 51 of 89 (57.3%) patients. The most common site for SN detection was the external iliac area. Metastatic nodes were detected in 21 of 89 (23.5%) patients. One false negative SN was obtained. Successful SN detection was more likely in patients younger than 50 yr (p=0.02) and with a history of preoperative conization (p=0.05). However, stage, histological type, surgical procedure and neoadjuvant chemotherapy showed no significant difference for SN detection rate. Therefore, the identification of SNs with isosulfan blue dye is feasible and safe. The SN detection rate was high in patients younger than 50 yr or with a history of preoperative conization

Targeting metastatic breast cancer with peptide epitopes derived from autocatalytic loop of Prss14/ST14 membrane serine protease and with monoclonal antibodies

Background In order to develop a new immunotherapeutic agent targeting metastatic breast cancers, we chose to utilize autocatalytic feature of the membrane serine protease Prss14/ST14, a specific prognosis marker for ER negative breast cancer as a target molecule. Methods The study was conducted using three mouse breast cancer models, 4 T1 and E0771 mouse breast cancer cells into their syngeneic hosts, and an MMTV-PyMT transgenic mouse strain was used. Prss14/ST14 knockdown cells were used to test function in tumor growth and metastasis, peptides derived from the autocatalytic loop for activation were tested as preventive metastasis vaccine, and monoclonal and humanized antibodies to the same epitope were tested as new therapeutic candidates. ELISA, immunoprecipitation, Immunofluorescent staining, and flow cytometry were used to examine antigen binding. The functions of antibodies were tested in vitro for cell migration and in vivo for tumor growth and metastasis. Results Prss14/ST14 is critically involved in the metastasis of breast cancer and poor survival rather than primary tumor growth in two mouse models. The epitopes derived from the specific autocatalytic loop region of Prss14/ST14, based on structural modeling acted as efficient preventive metastasis vaccines in mice. A new specific monoclonal antibody mAb3F3 generated against the engineered loop structure could reduce cell migration, eliminate metastasis in PyMT mice, and can detect the Prss14/ST14 protein expressed in various human cancer cells. Humanized antibody huAb3F3 maintained the specificity and reduced the migration of human breast cancer cells in vitro. Conclusion Our study demonstrates that Prss14/ST14 is an important target for modulating metastasis. Our newly developed hybridoma mAbs and humanized antibody can be further developed as new promising candidates for the use in diagnosis and in immunotherapy of human metastatic breast cancer.This work is supported in part by the National Research Foundation (NRF) grant funded by the Korea government (MEST) (No. 2013R1A1A2009892 and No. 2017R1A2B4008109) and Inha Univeristy Research Grant awarded to MGK and (No. 2015R1A2A1A15054021) to SHK

AP-1-Targeting Anti-Inflammatory Activity of the Methanolic Extract of Persicaria chinensis

In traditional Chinese medicine, Persicaria chinensis L. has been prescribed to cure numerous inflammatory disorders. We previously analyzed the bioactivity of the methanol extract of this plant (Pc-ME) against LPS-induced NO and PGE2 in RAW264.7 macrophages and found that it prevented HCl/EtOH-induced gastric ulcers in mice. The purpose of the current study was to explore the molecular mechanism by which Pc-ME inhibits activator protein- (AP-) 1 activation pathway and mediates its hepatoprotective activity. To investigate the putative therapeutic properties of Pc-ME against AP-1-mediated inflammation and hepatotoxicity, lipopolysaccharide- (LPS-) stimulated RAW264.7 and U937 cells, a monocyte-like human cell line, and an LPS/D-galactosamine- (D-GalN-) induced acute hepatitis mouse model were employed. The expression of LPS-induced proinflammatory cytokines including interleukin- (IL-) 1β, IL-6, and tumor necrosis factor-α (TNF-α) was significantly diminished by Pc-ME. Moreover, Pc-ME reduced AP-1 activation and mitogen-activated protein kinase (MAPK) phosphorylation in both LPS-stimulated RAW264.7 cells and differentiated U937 cells. Additionally, we highlighted the hepatoprotective and curative effects of Pc-ME pretreated orally in a mouse model of LPS/D-GalN-intoxicated acute liver injury by demonstrating the significant reduction in elevated serum AST and ALT levels and histological damage. Therefore, these results strongly suggest that Pc-ME could function as an antihepatitis remedy suppressing MAPK/AP-1-mediated inflammatory events