Myelin oligodendrocyte glycoprotein antibody-associated disease presenting as unilateral cerebral cortical encephalitis: a case report.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an autoimmune disorder with diverse clinical manifestations including myelitis, meningitis, encephalitis, and optic neuritis. MOGAD rarely presents with unilateral cerebral cortical encephalitis (CCE), rendering the diagnosis difficult in these cases. Furthermore, MOGAD is frequently accompanied by other autoimmune diseases such as thyroid disease or inflammatory bowel disease. Herein, we report a case of unilateral CCE with positive anti-myelin oligodendrocyte glycoprotein (MOG) antibodies. In addition, our patient presented with systemic symptoms as well as neurologic symptoms and was finally diagnosed with ulcerative colitis (UC). A 60-year-old female was admitted to the hospital with an acute onset of headache and fever. Neurological examination revealed left-sided homonymous hemianopsia with intermittent visual hallucinations as flickering red-circular spots in the left visual field. Brain magnetic resonance imaging showed focal hyperintensities and enhancement in the right temporo-parieto-occipital cortex. Electroencephalography indicated a focal seizure in the right occipital cortex. After the administration of an antiepileptic drug, the patient showed clinical and radiological improvements. She tested positive for serum anti-MOG antibodies and was diagnosed with anti-MOG-associated unilateral CCE. However, the gastrointestinal symptoms persisted, thus, a sigmoidoscopy was performed. The patient was diagnosed with comorbid UC. Steroids were administered to treat the UC and the gastrointestinal symptoms improved. To the best of our knowledge, this is the first case of MOGAD presenting as a unilateral CCE in Korea. This case highlights the clinical phenotypes of MOGAD and the need to assess comorbid autoimmune diseases in patients with MOGAD.

EMPHASISCHECKER: A Tool for Guiding Chart and Caption Emphasis.

Recent work has shown that when both the chart and caption emphasize the same aspects of the data, readers tend to remember the doubly-emphasized features as takeaways; when there is a mismatch, readers rely on the chart to form takeaways and can miss information in the caption text. Through a survey of 280 chart-caption pairs in real-world sources (e.g., news media, poll reports, government reports, academic articles, and Tableau Public), we find that captions often do not emphasize the same information in practice, which could limit how effectively readers take away the authors' intended messages. Motivated by the survey findings, we present EMPHASISCHECKER, an interactive tool that highlights visually prominent chart features as well as the features emphasized by the caption text along with any mismatches in the emphasis. The tool implements a time-series prominent feature detector based on the Ramer-Douglas-Peucker algorithm and a text reference extractor that identifies time references and data descriptions in the caption and matches them with chart data. This information enables authors to compare features emphasized by these two modalities, quickly see mismatches, and make necessary revisions. A user study confirms that our tool is both useful and easy to use when authoring charts and captions.

A Vax4HPV Mobile Application for Parents of Human Papillomavirus Vaccine-Eligible Children: Iterative Formative Assessments.

Although the human papillomavirus vaccine is efficacious, 40% of 13-year-old adolescents have been vaccinated for human papillomavirus. Implementing theory-based, user-centered applications can address this suboptimal coverage. This formative usability test aimed to develop a theory-based, user-centered interface to stimulate and inform parents' decision making on human papillomavirus vaccination and to help them act upon that decision. Iterative formative assessments were conducted through four focus groups of parents of children aged 9 to 14 years (N = 15). Participants discussed the desired content and features of a vaccine for human papillomavirus smartphone application while reviewing application prototypes. The discussions were recorded, transcribed verbatim, and then underwent qualitative content analysis. Four of the discovered themes were related to the content desired by parents: sources of information, facilitators of human papillomavirus vaccination, addressing the reasons for vaccine hesitancy, and gender-neutral content. The remaining three themes concerned the application's desirable designs and features: clear and descriptive interfaces, accessibility to broad groups of end users, and closing the intention-behavior gap. The need for adolescent human papillomavirus vaccination was generally well received by participants. This study found that theory-based, user-centered applications offering directions to appropriate clinics and human papillomavirus vaccine recommendations offered by nurses, can mitigate hesitancy by providing information via preferred routes and closing intention-behavior gaps.

Uniform deposition method of monodispersed SiO2 nanoparticles on a 300-mm Si wafer surface.

A study of the uniform deposition of nanoparticles across a 300-mm wafer was conducted to assess the uniformity of the wafer center-to-edge cleaning technique. A new method of particle deposition was devised different from the conventional method using electrostatic force. The strategy implements wafer rotation and deposition through principles of convection and diffusion. In this study, we focused on the effect of wafer rotation speed on particle deposition. After determining optimum conditions, fine results were obtained with a well-deposited shape and an excellent particle size uniformity of above 70% over the entire area of the wafer except in unusual cases. Deposition results were confirmed with KLA-Tencor Surfscan SP5 commonly used by foundries, and logic and memory manufacturers around the world to increase node development and production. The inherent index of the refraction value by Surfscan SP5 caused a particle size shift in measurement results. However, scanning electron microscopy and scanning mobility particle sizer analysis results revealed that 80-, 60-, 40-, 30-, and 20-nm-sized silica nanoparticles were well deposited on the wafer. Through this research, we believe that standard wafers processed with this particle deposition method will be useful for performance evaluation of wafer cleaning technology and calibration of wafer inspection technology during development.

Sensor Information Fusion by Integrated AI to Control Public Emotion in a Cyber-Physical Environment.

The cyber-physical system (CPS) is a next-generation smart system that combines computing with physical space. It has been applied in various fields because the uncertainty of the physical world can be ideally controlled using cyber technology. In terms of environmental control, studies have been conducted to enhance the effectiveness of the service by inducing ideal emotions in the service space. This paper proposes a CPS control system for inducing emotion based on multiple sensors. The CPS can expand the constrained environmental sensors of the physical space variously by combining the virtual space with the physical space. The cyber space is constructed in a Unity 3D space that can be experienced through virtual reality devices. We collect the temperature, humidity, dust concentration, and current emotion in the physical space as an environmental control elements, and the control illumination, color temperature, video, sound and volume in the cyber space. The proposed system consists of an emotion prediction module using modular Bayesian networks and an optimal stimulus decision module for deriving the predicted emotion to the target emotion based on utility theory and reinforcement learning. To verify the system, the performance is evaluated using the data collected from real situations.

Therapeutic Effect of Exogenous Truncated IK Protein in Inflammatory Arthritis.

Inhibitor K562 (IK) protein was first isolated from the culture medium of K562, a leukemia cell line. It is known to be an inhibitory regulator of interferon-γ-induced major histocompatibility complex class (MHC) II expression. Previously, we found that transgenic (Tg) mice constitutively expressing truncated IK (tIK) showed reduced numbers of pathogenic Th1 and Th17 cells, which are known to be involved in the development of rheumatoid arthritis (RA). Here, we investigated whether exogenous tIK protein has a therapeutic effect in arthritis in disease models and analyzed its mechanism. Exogenous tIK protein was produced in an insect expression system and applied to the collagen antibody-induced arthritis (CAIA) mouse disease model. Injection of tIK protein alleviated the symptoms of arthritis in the CAIA model and reduced Th1 and Th17 cell populations. In addition, treatment of cultured T cells with tIK protein induced expression of A20, a negative regulator of nuclear factor-κB (NFκB)-induced inflammation, and reduced expression of several transcription factors related to T cell activation. We conclude that exogenous tIK protein has the potential to act as a new therapeutic agent for RA patients, because it has a different mode of action to biopharmaceutical agents, such as tumor necrosis factor antagonists, that are currently used to treat RA.

Microneedles: quick and easy delivery methods of vaccines.

Vaccination is the most efficient method for infectious disease prevention. Parenteral injections such as intramuscular, intradermal, and subcutaneous injections have several advantages in vaccine delivery, but there are many drawbacks. Thus, the development of a new vaccine delivery system has long been required. Recently, microneedles have been attracting attention as new vaccination tools. Microneedle is a highly effective transdermal vaccine delivery method due to its mechanism of action, painlessness, and ease of use. Here, we summarized the characteristics of microneedles and the possibilities as a new vaccine delivery route.

Recombinant Adeno-Associated Virus Expressing Truncated IK Cytokine Diminishes the Symptoms of Inflammatory Arthritis.

IK can downregulate interferon-gamma-induced major histocompatibility complex (MHC) class II expression through the MHC class II transactivator, which suggests that IK can inhibit the interactions between immune cells. We delivered adeno-associated virus serotype 2 (AAV2) encoding the genes for truncated IK (tIK) or green fluorescent protein (GFP) to DBA1/J mice via intravenous injection. Seven weeks after injection, collagen-induced arthritis was induced in the AAV2-treated mice. AAV2-tIK injection reduced the severity of arthritis and the percentage of pathogenic Th17 cells compared with AAV2-GFP injection. These results suggest a novel gene therapy strategy for treatment of inflammatory arthritis.

IK acts as an immunoregulator of inflammatory arthritis by suppressing TH17 cell differentiation and macrophage activation.

Pathogenic T helper cells (TH) and macrophages have been implicated in the development of rheumatoid arthritis (RA), which can lead to severe synovial inflammation and bone destruction. A range of therapies have been widely used for RA, including specific monoclonal antibodies and chemical inhibitors against inflammatory cytokines produced by these cells. However, these have not been sufficient to meet the medical need. Here, we show that in transgenic mice expressing truncated IK (tIK) cytokine, inflammatory arthritis symptoms were ameliorated as the result of suppression of the differentiation of TH1 and TH17 cells and of macrophage activation. During inflammatory responses, tIK cytokine systemically regulated macrophage functions and TH17 cell differentiation through inactivation of the MAPK and NF-κB pathways. Interestingly, the level of tIK cytokine was higher in synovial fluid of RA patients compared with that in osteoarthritis (OA) patients. Our observations suggest that tIK cytokine can counterbalance the induction of inflammatory cells related to RA and thus could be a new therapeutic agent for the treatment of RA.

Nontoxic Formulations of Scintillation Nanocrystals for Use as X-ray Computed Tomography Contrast Agents.

X-ray computed tomography (CT) is currently one of the most powerful, noninvasive, clinical in vivo imaging techniques, which has resulted from advances in both X-ray device and contrast enhancement technologies. The present study demonstrates, for the first time, that metal tungstates (such as CaWO4) are promising contrast agents for X-ray, radiation, and CT imaging, because of the high X-ray mass attenuation of tungsten (W). We have developed a method of formulation, in which CaWO4 (CWO) nanoparticles (NPs) are encapsulated within a biocompatible poly(ethylene glycol-b-d,l-lactic acid) (PEG-PLA) block copolymer (BCP) capsule. We show that these PEG-PLA-encapsulated CWO NPs (170 ± 10 nm hydrodynamic diameter) produce a higher CT contrast (by a factor of about 2) than commercial iodine-based radiocontrast agents (e.g., Iohexol) at identical molar concentrations of W or I atoms. PEG-PLA-coated CWO NPs are chemically stable and completely nontoxic. It was confirmed that the maximum tolerated dose (MTD) of this material in mice is significantly higher (250 ± 50 mg per kg body weight following a single intravenous (IV) administration) than, for instance, commercially available dextran-coated iron oxide nanoparticles that are currently used clinically as MRI contrast agents (MTD in mice ≈ 168 mg/kg per dose IV). IV-injected PEG-PLA/CWO NPs caused no histopathologic damage in major excretory organs (heart, liver, lungs, spleen, and kidney). When an IV dose of 100 mg/kg was given to mice, the blood circulation half-life was measured to be about 4 h, and more than 90% of the NPs were cleared from the mice within 24 h via the renal and hepatobiliary systems. When intratumorally administered, PEG-PLA-coated CWO NPs showed complete retention in a tumor-bearing mouse model (measurements were made up to 1 week). These results suggest that PEG-PLA-coated CWO NPs are promising materials for use in CT contrast.

Apios americana Medik Extract Alleviates Lung Inflammation in Influenza Virus H1N1- and Endotoxin-Induced Acute Lung Injury.

Apios americana Medik (hereinafter Apios) has been reported to treat diseases, including cancer, hypertension, obesity, and diabetes. The therapeutic effect of Apios is likely to be associated with its anti-inflammatory activity. This study was conducted to evaluate the protective effects of Apios in animal models of acute lung injury induced by lipopolysaccharide (LPS) or pandemic H1N1 2009 influenza A virus (H1N1). Mice were exposed to LPS or H1N1 for 2-4 days to induce acute lung injury. The treatment groups were administered Apios extracts via oral injection for 8 weeks before LPS treatment or H1N1 infection. To investigate the effects of Apios, we assessed the mice for in vivo effects of Apios on immune cell infiltration and the level of pro-inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid, and histopathological changes in the lung. After induction of acute lung injury, the numbers of neutrophils and total cells were lower in the Apios-treated groups than in the non-Apios-treated LPS and H1N1 groups. The Apios groups tended to have lower levels of tumor necrosis factor-a and interleukin-6 in BAL fluid. In addition, the histopathological changes in the lungs were markedly reduced in the Apios-treated groups. These data suggest that Apios treatment reduces LPS- and H1N1-induced lung inflammation. These protective effects of Apios suggest that it may have therapeutic potential in acute lung injury.

Metabolomic Analysis Reveals Cyanidins in Black Raspberry as Candidates for Suppression of Lipopolysaccharide-Induced Inflammation in Murine Macrophages.

The extracts produced by multisolvent extraction and subfractionation with preparative liquid chromatography of black raspberry (Rubus coreanus Miquel) cultivated in Gochang, South Korea, were tested for their anti-inflammatory effects. The metabolomic profiling and analysis by orthogonal partial least-squares discriminant analysis (OLPS-DA) suggested that cyanidin, cyanidin-3-glucoside (C3G), and cyanidin-3-rutinoside (C3R) were key components for the anti-inflammatory responses in the most active fraction BF3-1, where they were present at 0.44, 1.26, and 0.56 µg/mg of BF3-1, respectively. Both BF3-1 and mixture of these cyanidins at the same ratio reduced lipopolysaccharide (LPS)-induced protein level of iNOS expression and suppressed mRNA and protein expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß through inhibiting the phosphorylation of mitogen-activated protein kinases (MAPKs) and STAT3 in murine macrophage RAW264.7 cells. Overall, the results suggested that co-administration of cyanidin, C3G, and C3R is more effective than that of cyanidin alone and that the coexistence of these anthocyanin components in black raspberry plays a vital role in regulating LPS-induced inflammation even at submicromolar concentrations, making it possible to explain the health beneficial activity of its extracts.

Adenine suppresses IgE-mediated mast cell activation.

Nucleobase adenine is produced by dividing human lymphoblasts mainly from polyamine synthesis and inhibits immunological functions of lymphocytes. We investigated the anti-allergic effect of adenine on IgE-mediated mast cell activation in vitro and passive cutaneous anaphylaxis (PCA) in mice. Intraperitoneal injection of adenine to IgE-sensitized mice attenuated IgE-mediated PCA reaction in a dose dependent manner, resulting in a median effective concentration of 4.21 mg/kg. In mast cell cultures, only adenine among cytosine, adenine, adenosine, ADP and ATP dose-dependently suppressed FcɛRI (a high affinity receptor for IgE)-mediated degranulation with a median inhibitory concentration of 1.6mM. It also blocked the production of LTB4, an inflammatory lipid mediator, and inflammatory cytokines TNF-α and IL-4. In addition, adenine blocked thapsigargin-induced degranulation which is FcɛRI-independent but shares FcɛRI-dependent signaling events. Adenine inhibited the phosphorylation of signaling molecules important to FcɛRI-mediated allergic reactions such as Syk, PLCγ2, Gab2, Akt, and mitogen activated protein kinases ERK and JNK. From this result, we report for the first time that adenine inhibits PCA in mice and allergic reaction by inhibiting FcɛRI-mediated signaling events in mast cells. Therefore, adenine may be useful for the treatment of mast cell-mediated allergic diseases. Also, the upregulation of adenine production may provide another mechanism for suppressing mast cell activity especially at inflammatory sites.

Nucleus accumbens lesions decrease sensitivity to rapid changes in the delay to reinforcement.

Both humans and non-humans discount the value of rewards that are delayed or uncertain, and individuals that discount delayed rewards at a relatively high rate are considered impulsive. To investigate the neural mechanisms that mediate delay discounting, the present study examined the effects of excitotoxic lesions of the nucleus accumbens (NAC) on discounting of reward value by delay and probability. Rats were trained on delay (n=24) or probability discounting (n=24) tasks. Following training, excitotoxic lesions of the NAC were made by intracranial injections of 0.5 microl 0.15 M quinolinic acid (n=12) or vehicle (n=12) aimed at the NAC (AP +1.6, ML +/-1.5, DV -7.1). NAC lesions did not alter performance in animals tested with a constant delay (4s) or probability (0.4) of reinforcement. However, when tested with between session changes in the delay (0, 1, 2, 4, and 8s) of reinforcement, the lesioned rats had flatter discount curves than the sham group, indicating that they were less sensitive to frequent changes in the delay to reward. In contrast, the NAC lesions did not affect discounting of probabilistic rewards. NAC lesions impaired the ability to adapt to frequent between session changes in the delay to reward but did not increase or decrease discounting when the delay was held constant across sessions. NAC lesions may disrupt the ability of the animals to predict the timing of delayed rewards when the delay to reward is changed frequently.