Risk of uveitis in patients with psoriasis in Korea: A nationwide population-based cohort study.

BACKGROUND: Evidence for the association between psoriasis and uveitis according to the severity of psoriasis including psoriatic arthritis (PsA) and type of uveitis is lacking, and there are no data on the frequency or timing of recurrence of uveitis in patients with psoriasis. OBJECTIVES: We aimed to evaluate the risk of first occurrence and recurrence of uveitis in patients with psoriasis in the Korean population. We further evaluated the risk of uveitis according to the severity of psoriasis, comorbidity of PsA and location of uveitis. METHODS: In a nationwide retrospective cohort study, we compared 317,940 adult patients who had psoriasis with 635,880 matched controls. Incidence rates (IRs) and estimated IR ratios of the first occurrence and recurrence of uveitis were calculated using survival analysis and Poisson regression, respectively. RESULTS: The rate of uveitis incidence and uveitis recurrence in patients with psoriasis was 1.18 and 2.31 per 1000 person-years, respectively. Compared to the controls, the IR ratios of development and recurrence of uveitis in patients with psoriasis were 1.14 (95% CI 1.08, 1.2) and 1.16 (95% CI 1.12, 1.21), respectively. The recurrence rate of uveitis was highest within 3 years after the onset of psoriasis. The corresponding IR ratios for uveitis recurrence in patients with mild psoriasis, severe psoriasis and PsA were 1.11 (1.06, 1.16), 1.24 (1.16, 1.33) and 1.49 (1.31, 1.7), respectively. Patients with psoriasis had an increased risk of recurrence of anterior uveitis, and patients with both psoriasis and PsA had an increased risk of recurrence of both anterior-uveitis and panuveitis. CONCLUSIONS: Patients with psoriasis had a higher risk of both development and recurrence of uveitis, especially with severe psoriasis and PsA. The timing of uveitis recurrence was related to the onset of psoriasis, and patients who had psoriasis with PsA had an increased risk of vision-threatening panuveitis.

Therapeutic Hydrogel Patch to Treat Atopic Dermatitis by Regulating Oxidative Stress.

Atopic dermatitis (AD) is a chronic inflammatory disease associated with unbalanced immune responses in skin tissue. Although steroid drugs and antihistamines are generally used to treat AD, continuous administration causes multiple side effects. High oxidative stress derived from reactive oxygen species (ROS) has been implicated in the pathogenesis of AD. A high level of ROS promotes the release of pro-inflammatory cytokines and T-cell differentiation, resulting in the onset and deterioration of AD. Here, we report a therapeutic hydrogel patch suppressing the high oxidative stress generated in AD lesions. The hydrogel embedded with ROS-scavenging ceria nanoparticles leads to the decrease of both extracellular and intracellular ROS and exhibits cytoprotective effects in a highly oxidative condition. AD-induced mouse model studies show enhanced therapeutic outcomes, including a decrease in the epidermal thickness and levels of AD-associated immunological biomarkers. These findings indicate that a ROS-scavenging hydrogel could be a promising therapeutic hydrogel patch for treating and managing AD.

A comparison of the influencing factors of chronic pain and quality of life between older Koreans and Korean-Americans with chronic pain: a correlational study.

BACKGROUND: Chronic pain is one of the most common health problems for older adults worldwide and is likely to result in lower quality of life. Living in a different culture may also influence chronic pain and quality of life in older adults. The purpose of this study was to explore how multifaceted elements affect chronic pain and quality of life in older Koreans living in Korea and in older Korean-Americans (KAs) living in the USA. METHODS: We conducted a secondary data analysis of data from 270 adults aged 65 years or over (138 Koreans and 132 KAs). We compared the effects of multifaceted elements on pain and quality of life by testing structural equation models (SEMs) for each group, using a maximum likelihood estimation and bootstrapping. RESULTS: SEMs for both Korean and KAs showed that age and depressive symptoms directly affected quality of life. The number of comorbidities and depressive symptoms had mediating effects on quality of life through chronic pain in both groups. In older Koreans only, perceived financial status directly affected quality of life. In older KAs only, sleep quality indirectly affected quality of life through chronic pain. CONCLUSION: The data showed that multimorbidity and depressive symptoms play critical roles for explaining chronic pain in older Koreans and KAs and ultimately negatively influence quality of life. Future intervention program to improve quality of life in older adults with chronic pain should consider the different cultural aspects affecting quality of life for Koreans and KAs.

Contact Tracing during Coronavirus Disease Outbreak, South Korea, 2020.

We analyzed reports for 59,073 contacts of 5,706 coronavirus disease (COVID-19) index patients reported in South Korea during January 20-March 27, 2020. Of 10,592 household contacts, 11.8% had COVID-19. Of 48,481 nonhousehold contacts, 1.9% had COVID-19. Use of personal protective measures and social distancing reduces the likelihood of transmission.

Intra-Ethnic Differences in Chronic Pain and the Associated Factors: An Exploratory, Comparative Design.

PURPOSE: To describe and compare the levels of pain severity and pain interference, pain catastrophizing, and associated factors between elderly Koreans living in South Korea and Korean Americans living in the United States with chronic pain. METHODS: An exploratory, comparative design was used for this study. A total of 270 individuals (138 Koreans living in South Korea and 132 Korean Americans living in the United States), aged more than 65 years, with self-reported chronic pain, and defined as at least 3 months of persistent musculoskeletal pain, is included. Outcome variables were pain severity, pain interference, and pain catastrophizing. Multivariate linear regression was conducted to examine factors associated with the outcome variables. RESULTS: In multivariate analysis, Korean Americans had higher levels of pain severity and pain catastrophizing than Koreans. Depressive symptoms, sleep quality, and health-related quality of life were significant factors for pain severity, pain interference, and pain catastrophizing for both groups. Among those factors, health-related quality of life was the most significant factor for predicting pain severity and pain interference, whereas depressive symptoms were the most significant factor for predicting pain catastrophizing for both groups. CONCLUSIONS: Intra-ethnic differences in pain severity and pain catastrophizing were found between elderly Koreans living in South Korea and Korean Americans living in the United States. CLINICAL RELEVANCE: Because unfamiliar sociocultural and environmental factors may influence the pain responses, cultural differences and language barriers should be taken into account in pain research and management strategies for Asian immigrants in the United States. Psychological factors, including depressive symptoms, sleep quality, and health-related quality of life, should also be considered in chronic pain management for both elderly Koreans and Korean Americans.

Electrochemical Characteristics of All-Solid Lithium Ion Battery with Lithium Titanate/Lithium Lanthanum Zirconium Oxide Composite Electrode.

Composite anodes for all solid-state lithium secondary batteries based on lithium titanate (Li4Ti5O12) were fabricated by a wet process. The effect of the content of polyethylene oxide in the lithium titanate composite anode on the interfacial control for enhancing the ionic conductivity and binding between the constituent materials in the electrode was examined. The content of Super-P and garnet-type lithium lanthanum zirconium oxide in the composite lithium titanate electrode was fixed and the electrochemical characteristics of a half-cell were evaluated as a function of the lithium titanate and polyethylene oxide content in the electrode, where the polyethylene oxide content was varied from 35-70 wt%. A maximum discharge capacity of about 160 mAh g-1 was obtained with the electrode comprising lithium titanate, lithium lanthanum zirconium oxide, Super-P, and polyethylene oxide in a weight ratio of 40:10:10:40. This value is about 94% of the theoretical capacity (170 mAh g-1) of the lithium titanate electrode, and was almost equal to the half-cell capacity of the liquid-type congener. Furthermore, when this composite lithium titanate electrode was fabricated and evaluated in the full cell of an all-solid lithium secondary battery, a discharge capacity of about 140 mAh g-1 was obtained.

Clinical and Genetic Characteristics Analysis of Korean Patients with Stargardt Disease Using Targeted Exome Sequencing.

PURPOSE: To investigate genetic mutations in Korean patients with Stargardt disease (STGD) using exome sequencing, and to analyze the correlations between genetic mutations and clinical phenotypes. METHODS: Peripheral venous blood was obtained from 24 clinically diagnosed Korean STGD patients, followed by extraction of genomic DNAs. Using exome sequencing we investigated gene mutations for the adenosine triphosphate-binding cassette, subfamily A, member 4 (ABCA4) elongation of very-long-chain fatty acids 4 (ELOVL4), and prominin 1 (PROM1), and confirmed gene mutations by the direct sequencing of polymerase chain reaction products. RESULTS: ABCA4 mutations were confirmed in 17 of 24 patients, and 12 novel mutations were identified. ELOVL4 and PROM1 gene mutations were not identified in this study. We also identified 16 previously reported mutations related to STGD1. In patients whose disease symptoms occurred before 20 years of age, visual acuity was poorer and atrophic flecks were more frequently found. In addition, more ABCA4 mutations were found in patients who had choroidal silence or atrophic flecks. CONCLUSIONS: Novel ABCA4 gene mutations were found in Korean patients with STGD1. This study will facilitate better understanding of the relationships between ABCA4 gene mutations and clinical symptoms in Korean patients.

Exon 9 skipping of apoptotic caspase-2 pre-mRNA is promoted by SRSF3 through interaction with exon 8.

Alternative splicing plays an important role in gene expression by producing different proteins from a gene. Caspase-2 pre-mRNA produces anti-apoptotic Casp-2S and pro-apoptotic Casp-2L proteins through exon 9 inclusion or skipping. However, the molecular mechanisms of exon 9 splicing are not well understood. Here we show that knockdown of SRSF3 (also known as SRp20) with siRNA induced significant increase of endogenous exon 9 inclusion. In addition, overexpression of SRSF3 promoted exon 9 skipping. Thus we conclude that SRSF3 promotes exon 9 skipping. In order to understand the functional target of SRSF3 on caspase-2 pre-mRNA, we performed substitution and deletion mutagenesis on the potential SRSF3 binding sites that were predicted from previous reports. We demonstrate that substitution mutagenesis of the potential SRSF3 binding site on exon 8 severely disrupted the effects of SRSF3 on exon 9 skipping. Furthermore, with the approach of RNA pulldown and immunoblotting analysis we show that SRSF3 interacts with the potential SRSF3 binding RNA sequence on exon 8 but not with the mutant RNA sequence. In addition, we show that a deletion of 26nt RNA from 5' end of exon 8, a 33nt RNA from 3' end of exon 10 and a 2225nt RNA from intron 9 did not compromise the function of SRSF3 on exon 9 splicing. Therefore we conclude that SRSF3 promotes exon 9 skipping of caspase-2 pre-mRNA by interacting with exon 8. Our results reveal a novel mechanism of caspase-2 pre-mRNA splicing.

Late-Onset Slowly Progressing Cone/Macular Dystrophy in Patients With the Biallelic Hypomorphic Variant p.Arg1933Ter in RP1.

Purpose: Homozygous hypomorphic variants of the RP1 gene, including c.5797C>T, p.Arg1933Ter, have traditionally been considered non-pathogenic. This study aimed to elucidate the clinical manifestations of late-onset, slowly progressive cone/macular dystrophy in patients homozygous for p.Arg1933Ter in the RP1 gene. Methods: Five patients with biallelic p.Arg1933Ter in RP1 were retrospectively recruited, and their clinical profiles were analyzed. Copy number variation analysis and Alu insertion assessment of genes associated with inherited retinal diseases were conducted. The results of comprehensive ophthalmological examinations, multimodal imaging, and full-field electroretinogram tests were analyzed. Results: No specific sequencing errors or structural variations associated with the clinical phenotypes were identified. Alu element insertion in RP1 was not detected. The mean ± SD age at the first visit was 62.2 ± 9.8 years, with symptoms typically starting between 45 and 50 years of age. Two patients exhibited a mild form of cone/macular dystrophy, characterized by a relatively preserved fundus appearance and blurring of the ellipsoid zone on optical coherence tomography. Three patients had late-onset cone/macular dystrophy with significant atrophy. Conclusions: To our knowledge, this study is the first to report that a homozygous hypomorphic variant of RP1, previously considered non-pathogenic, leads to cone/macular dystrophy. Translational Relevance: The study introduces novel possibilities suggesting that the homozygous hypomorphic variant of RP1 may be linked to variant pathogenicity.

MR-based outcome predictors of lumbar transforaminal epidural steroid injection for lumbar radiculopathy caused by herniated intervertebral disc.

OBJECTIVES: To evaluate the MR-based outcome predictors of lumbar transforaminal epidural steroid injection (ESI) for lumbar radiculopathy caused by herniated intervertebral disc (HIVD). METHODS: A total of 149 patients (male/female 75:74; mean age 51.5 years) with the very worst (87 patients) or the very best outcome (62 patients) after ESI were enrolled in this study. They were selected from 1,881 patients who underwent lumbar transforaminal ESI for lumbar radiculopathy caused by HIVD from January 2007 to December 2008. Two radiologists reviewed MR in consensus. Chi-square test and Fisher's exact test were used to evaluate the difference between the two groups. RESULTS: HIVD in the foraminal-extraforaminal zone were significantly more common in the very best outcome group (16/24, 66.6 %) than HIVD in the central-subarticular zone (46/125, 36.8 %) (P = 0.012). Other factors such as HIVD zone, T2-high signal, relation to nerve root, corner change, Modic change, disc height loss, grade of disc degeneration, and osteophyte were not statistically significant. CONCLUSION: HIVD in the foraminal or extraforaminal zone is the only good MR-based outcome predictor of lumbar transforamial ESI for lumbar radiculopathy.

Orally Administrated Inflamed Colon-Targeted Nanotherapeutics for Inflammatory Bowel Disease Treatment by Oxidative Stress Level Modulation in Colitis.

Inflammatory bowel disease (IBD) is characterized by an inappropriate and persistent inflammatory immune response and is often accompanied by excessive reactive oxygen species (ROS) production. For effective IBD treatment, there is a high demand for safe and targeted therapy that can be orally administered. In this study, we aimed to propose the use of inflamed colon-targeted antioxidant nanotherapeutics (ICANs) for in situ oxidative stress level modulation in colitis. ICANs consist of mesoporous silica nanoparticles (MSNs) with surface-attached ROS-scavenging ceria nanoparticles (CeNPs), which are further coated with poly(acrylic acid) (PAA) to facilitate preferential adherence to inflamed colon tissues through electrostatic interaction. We achieved a high ROS-scavenging property that remained effective even after artificial gastrointestinal fluid incubation by optimization of the molecular weight and PAA-coating pH. The orally administered ICANs demonstrated enhanced adherence to inflamed colon tissues in an acute inflammation mouse model of IBD induced by dextran sulfate sodium. This targeted delivery resulted in gut microenvironment modulation by regulating redox balance and reducing inflammatory cell infiltration, thereby suppressing the colitis-associated immune response. These findings highlight the potential of noninvasive ICANs as a promising candidate for treating inflammatory intestinal diseases by oxidative stress level modulation in colitis.

FITC-Labeled RGD Peptides as Novel Contrast Agents for Functional Fluorescent Angiographic Detection of Retinal and Choroidal Neovascularization.

The development of choroidal neovascularization (CNV) is a crucial factor in the pathophysiology and prognosis of exudative age-related macular degeneration (AMD). Therefore, the detection of CNV is essential for establishing an appropriate diagnosis and treatment plan. Current ophthalmic imaging techniques, such as fundus fluorescent angiography and optical coherence tomography, have limitations in accurately visualizing CNV lesions and expressing CNV activity, owing to issues such as excessive dye leakage with pooling and the inability to provide functional information. Here, using the arginine-glycine-aspartic acid (RGD) peptide's affinity for integrin αvß3, which is expressed in the neovascular endothelial cells in ocular tissues, we propose the use of fluorescein isothiocyanate (FITC)-labeled RGD peptide as a novel dye for effective molecular imaging of CNV. FITC-labeled RGD peptides (FITC-RGD2), prepared by bioconjugation of one FITC molecule with two RGD peptides, demonstrated better visualization and precise localization of CNV lesions than conventional fluorescein dyes in laser-induced CNV rodent models, as assessed using various imaging techniques, including a commercially available clinical fundus camera (Optos). These results suggest that FITC-RGD2 can serve as an effective novel dye for the diagnosis of neovascular retinal diseases, including AMD, by enabling early detection and treatment of disease occurrence and recurrence after treatment.

Therapeutic Extracellular Vesicles from Tonsil-Derived Mesenchymal Stem Cells for the Treatment of Retinal Degenerative Disease.

BACKGROUND: Retinal degenerative disease (RDD), one of the most common causes of blindness, is predominantly caused by the gradual death of retinal pigment epithelial cells (RPEs) and photoreceptors due to various causes. Cell-based therapies, such as stem cell implantation, have been developed for the treatment of RDD, but potential risks, including teratogenicity and immune reactions, have hampered their clinical application. Stem cell-derived extracellular vesicles (EVs) have recently emerged as a cell-free alternative therapeutic strategy; however, additional invasiveness and low yield of the stem cell extraction process is problematic. METHODS: To overcome these limitations, we developed therapeutic EVs for the treatment of RDD which were extracted from tonsil-derived mesenchymal stem cells obtained from human tonsil tissue discarded as medical waste following tonsillectomy (T-MSC EVs). To verify the biocompatibility and cytoprotective effect of T-MSC EVs, we measured cell viability by co-culture with human RPE without or with toxic all-trans-retinal. To elucidate the cytoprotective mechanism of T-MSC EVs, we performed transcriptome sequencing using RNA extracted from RPEs. The in vivo protective effect of T-MSC EVs was evaluated using Pde6b gene knockout rats as an animal model of retinitis pigmentosa. RESULTS: T-MSC EVs showed high biocompatibility and the human pigment epithelial cells were significantly protected in the presence of T-MSC EVs from the toxic effect of all-trans-retinal. In addition, T-MSC EVs showed a dose-dependent cell death-delaying effect in real-time quantification of cell death. Transcriptome sequencing analysis revealed that the efficient ability of T-MSC EVs to regulate intracellular oxidative stress may be one of the reasons explaining their excellent cytoprotective effect. Additionally, intravitreally injected T-MSC EVs had an inhibitory effect on the destruction of the outer nuclear layer in the Pde6b gene knockout rat. CONCLUSIONS: Together, the results of this study indicate the preventive and therapeutic effects of T-MSC EVs during the initiation and development of retinal degeneration, which may be a beneficial alternative for the treatment of RDD.

Development of a novel Korean reading chart.

CLINICAL RELEVANCE: Measuring reading ability is a crucial part of assessing patients who complain of reduced vision. Foreign language versions of such charts need to be developed and validated. BACKGROUND: It is difficult to measure or predict Korean reading ability due to a lack of a representative reading charts in Korean, and previous charts have limited capacity to detect deficits in reading ability among Korean patients with eye diseases. METHODS: Two printed versions of the reading chart were created. Thirty-four patients with no change in vision in the last three months and no expected change in vision in the next four weeks were included in this study. The results were validated by testing 13 normal-sighted adults (group 1), 14 patients with various macular diseases whose visual acuity was equal or better than 0.5 logarithm of the minimum angle of resolution (logMAR) (group 2), and seven patients with various macular diseases whose visual acuities were between 1.3 logMAR and 0.5 logMAR (group 3). Inter-chart and intra-subject repeatabilities were assessed for maximum reading speed (MRS) and critical print size (CPS). RESULTS: A total of 38 sentences were tested on 34 adults in three groups. Groups 1 and 2 did not differ significantly in terms of MRS and CPS. The MRS was lower in group 3, for each chart and between visits. The CPS was larger in group 3, for each chart and between visits, with the exception of chart 2 during visit one. With regard to test-retest reliability, the intraclass correlation co-efficients (ICCs) for chart 1 and chart 2 were more than 0.900. With regard to inter-chart reliability, the ICCs were more than 0.892, respectively. CONCLUSION: The reading chart developed in this study was reliable in producing consistent results among a normal Korean population and patients with various macular diseases.

Immunosuppressive biomaterial-based therapeutic vaccine to treat multiple sclerosis via re-establishing immune tolerance.

Current therapies for autoimmune diseases, such as multiple sclerosis (MS), induce broad suppression of the immune system, potentially promoting opportunistic infections. Here, we report an immunosuppressive biomaterial-based therapeutic vaccine carrying self-antigen and tolerance-inducing inorganic nanoparticles to treat experimental autoimmune encephalomyelitis (EAE), a mouse model mimicking human MS. Immunization with self-antigen-loaded mesoporous nanoparticles generates Foxp3+ regulatory T-cells in spleen and systemic immune tolerance in EAE mice, reducing central nervous system-infiltrating antigen-presenting cells (APCs) and autoreactive CD4+ T-cells. Introducing reactive oxygen species (ROS)-scavenging cerium oxide nanoparticles (CeNP) to self-antigen-loaded nanovaccine additionally suppresses activation of APCs and enhances antigen-specific immune tolerance, inducing recovery in mice from complete paralysis at the late, chronic stage of EAE, which shows similarity to chronic human MS. This study clearly shows that the ROS-scavenging capability of catalytic inorganic nanoparticles could be utilized to enhance tolerogenic features in APCs, leading to antigen-specific immune tolerance, which could be exploited in treating MS.

Acute Effect of Evolocumab on Lipoprotein(a) Level and Inflammation in Patients with Coronary Artery Disease.

Background: Several studies have shown that high plasma lipoprotein(a) concentrations are associated with an increased risk of arteriosclerotic cardiovascular disease. Thus, Lp(a) has emerged as a new therapeutic target. Circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are new lipid-lowering agents that reduce low-density lipoprotein cholesterol as well as Lp(a). Methods: We analyzed the short-term effects of one-time administration of evolocumab (a PCSK9 inhibitor) on the lipid profiles (especially Lp(a)) and inflammatory markers in Korean patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI). Sixty-four patients with CAD who underwent PCI were enrolled in this trial. Evolocumab (140 mg) was administered to patients within 24 h after PCI. Lipid profiles and inflammatory marker levels were measured at baseline and 2 weeks later. Results: The PCSK9 inhibitor significantly reduced the baseline levels of Lp(a) (−9.2 mg/dL, p < 0.001), but high-sensitivity C-reactive protein (+0.07 mg/dL, p = 0.272) was not significantly different after 2 weeks. In patients with an Lp(a) level of 50 mg/dL or more, the Lp(a) level decreased significantly by approximately 30%, from 95.6 mg/dL to 67.0 mg/dL (p < 0.001). Conclusions: One-time PCSK9 inhibitor treatment may be effective in lowering Lp(a) levels in Korean patients in the short term.

Correlations Between Coronary Artery Disease, Coronary Artery Calcium Score, and Lipoprotein(a) Level in Korea.

Background: Lipoprotein(a) (Lp(a)) levels are associated with coronary artery disease (CAD) and aortic valve calcification. This study aimed to determine the correlation between Lp(a) levels and coronary artery calcium (CAC) scores in patients who underwent coronary computed tomography angiography (CCTA). Methods: This was a single-center observational study. The patients had not been previously diagnosed with CAD and underwent CCTA and Lp(a) measurement in a three-month timeframe. Coronary angiography and further management were performed according to the physician's decision. Of the 252 patients, 81 and 171 patients underwent coronary revascularization and received medical treatment only, respectively. To examine the relationship between Lp(a) and CAC score and between Lp(a) and CAD, we divided the patients by Lp(a) level (50 mg/dL) and CAC score (400). Results: No relationship was observed between Lp(a) and CAD or other risk factors for CAD. There were no differences in the ratio of patients who underwent coronary revascularization or in the CAC score according to an Lp(a) level of 50 mg/dL. There was no difference in Lp(a) level at a CAC score of 400. The proportion of patients who underwent coronary revascularization was high in the high CAC score group (50.6% vs 23.7%, p = 0.000). No association was observed between Lp(a) level and CAC score in the Spearman correlation (0.000, p < 0.998). Conclusion: Correlations between Lp(a) level and CAC score and between Lp(a) and CAD were not observed in this Korean cohort study. However, a high CAC score was correlated with coronary revascularization.

Facile Room-Temperature Synthesis of Cerium Carbonate and Cerium Oxide Nano- and Microparticles Using 1,1'-Carbonyldiimidazole and Imidazole in a Nonaqueous Solvent.

Ceria nanoparticles (CeONPs) are versatile materials due to their unique catalytic properties, and cerium carbonate particles (CeCbPs) have been widely used as precursors for cerium oxide due to their ease of production. Urea is a widely used precipitant and a source of carbonate ions for the synthesis of CeONPs and CeCbPs, and the reaction temperature is important for controlling the rate of urea decomposition. However, the precise control of the temperature is often difficult, especially in large-scale reactions. Herein, we propose a homogeneous precipitation method that uses 1,1'-carbonyldiimidazole (CDI) and imidazole in acetone without heating. The decomposition rate of CDI can be controlled by the amount of water in the reaction mixture. In the synthesis of CeCbPs, unique particle morphologies of plate-, flying-saucer-, and macaron-like shapes and a wide range of sizes from 180 nm to 13 µm can be achieved by adjusting the amount of CDI, imidazole, and water in the reaction. These CeCbPs are transformed into ceria particles by calcination while maintaining their characteristic morphology. Moreover, the direct synthesis of 130 nm spherical CeONPs was possible by decreasing the amount of CDI in the reaction and the mixing time. These nanoparticles exhibited higher production efficiency and superior reactive oxygen species (ROS) scavenging properties compared to the other CeONPs obtained from calcination. These results demonstrate a novel method using CDI and imidazole in the synthesis of CeONPs and CeCbPs without the aid of a heating process, which may be useful in the large-scale synthesis and application of CeO nanomaterials.

Alternative Activation of Macrophages through Interleukin-13-Loaded Extra-Large-Pore Mesoporous Silica Nanoparticles Suppresses Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) treatment via cytokine-mediated immunomodulation has been hampered by the difficulty with which cytokines can be stably and noninvasively delivered to the central nervous system. Here, we show that interleukin (IL)-13 packaged in extra-large-pore mesoporous silica nanoparticles (XL-MSNs) is protected from degradation and directs the alternative activation of macrophages both in vitro and in vivo. Furthermore, the noninvasive intranasal delivery of IL-13-loaded XL-MSNs ameliorated the symptoms of experimental autoimmune encephalomyelitis, a murine model of MS, accompanied by the induction of chemokines orchestrating immune cell infiltration. These results demonstrate the therapeutic potential of IL-13-loaded XL-MSNs for MS patients.

Vascular Protective Effects of New Oral Anticoagulants in Patients with Atrial Fibrillation.

This study was designed to determine the efficacy of a new oral anticoagulant (NOAC) therapy for the prevention of endothelial dysfunction and atherosclerosis progression in patients with atrial fibrillation (AF). Sixty-five AF patients with a CHA2DS2-VASc score ≥2 without previous history of cardiovascular disease were registered and randomly assigned to either an NOAC group (dabigatran or rivaroxaban) or the warfarin group. Reactive hyperemia peripheral arterial tonometry (RH-PAT) measurements reflecting endothelial function were taken using Endo-PAT2000. Carotid intima-media thickness (IMT) was measured at baseline, 12 months, and 24 months, and several biomarkers were also analyzed. For the primary end point, the reactive hyperemia index (RHI) for the NOAC group was 1.5 ± 0.4 and that for the warfarin group was 1.6 ± 0.5. The left and right carotid IMT was 0.7 mm in the NOAC groups and 0.8 mm in the warfarin group. At 12 months, RHI was 1.6 ± 0.3 for the dabigatran group, 1.6 ± 0.5 for the rivaroxaban group, and 1.6 ± 0.3 for the warfarin group. The three groups did not differ statistically with respect to change in left and right carotid IMT at 12 and 24 months, respectively. The biomarkers for endothelial function and atherosclerosis were not significantly different. There was a trend of reduced P-selectin levels in the NOAC group compared to the warfarin group. In patients with AF, there were no significant differences in the prevention of endothelial dysfunction and atherosclerosis progression between the NOAC and warfarin groups.