Risk of cardiovascular disease associated with long-term use of non-steroidal anti-inflammatory drugs in ankylosing spondylitis.

OBJECTIVE: To examine the risk of cardiovascular disease associated with long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) in a large real-world ankylosing spondylitis (AS) cohort. METHODS: This nationwide population-based cohort study used data from the Korean National Health Insurance Database. Patients aged ≥18 years old who were newly diagnosed with AS without prior cardiovascular disease between January 2010 and December 2018 were included in this study. Controls without AS were randomly selected by age, sex, and index year. The primary outcome was cardiovascular disease, a composite outcome of ischemic heart disease, stroke, or congestive heart failure. Long-term use of NSAIDs was defined as use of NSAIDs for >365 cumulative defined daily doses. The association between long-term use of NSAIDs and incident cardiovascular disease was examined in both AS and non-AS populations. RESULTS: Among 19 775 patients with AS and 59 325 matched controls without AS, there were 1,663 and 4,308 incident cases of cardiovascular disease, showing an incidence of 16.9 and 13.8 per 1,000 person-years, respectively. Long-term use of NSAIDs was associated with increased risk of cardiovascular disease in non-AS controls (adjusted hazard ratio [aHR], 1.64; 95% CI, 1.48-1.82). In contrast, long-term use of NSAIDs did not increase the risk of cardiovascular disease in AS patients (aHR, 1.06; 95% CI, 0.94-1.20; adjusted for age, sex, socioeconomic status, body mass index, smoking status, hypertension, diabetes, hyperlipidemia, and tumor necrosis factor inhibitor use). CONCLUSION: Prolonged NSAID treatment in AS patients may not be as harmful as in the general population regarding cardiovascular risk.

Socioeconomic inequality of health-related quality of life in cancer survivors in South Korea.

BACKGROUND: We investigated the inequalities in health-related quality of life (HRQoL) among cancer survivors in Korea, focusing on income and education levels. The slope index of inequality (SII) and relative index of inequality (RII) were utilized to analyze these disparities. METHODS: Data from the Korea National Health and Nutrition Examination Survey (KNHANES) conducted between 2007 and 2021 was analyzed. The HRQoL was assessed using the EQ-5D questionnaire, which included five problem areas: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. Logistic regression was employed to calculate the odds ratios (ORs) for each education and income level, indicating the probability of reporting problems. Furthermore, the slope index of inequality (SII) and relative index of inequality (RII) were calculated to evaluate the inequalities in HRQoL. RESULTS: Among the 3396 cancer survivors, a considerable proportion reported pain/discomfort (29.6%) and mobility problems (21.1%). The logistic regression results demonstrated a higher likelihood of experiencing problems in all five EQ-5D items among individuals with lower income or education levels. Specifically, compared to the high-income group, the adjusted ORs for mobility problems were 2.19, 1.64, and 1.08 for the low, low-medium, and medium-high-income groups, respectively (p-value < 0.05). Notably, significant income inequalities in HRQoL problems were observed, with the greatest disparities seen in self-care and usual activity problems, as indicated by the SII and RII values. CONCLUSION: Socioeconomic disparities in HRQoL exist among cancer survivors in Korea, particularly related to income levels. Addressing the financial burdens of cancer treatment for individuals with low-income levels may help improve their HRQoL and mitigate these inequalities.

Bioactive Properties of Enzymatic Gelatin Hydrolysates Based on In Silico, In Vitro, and In Vivo Studies.

This current study aims to analyze the potential bioactivities possessed by the enzymatic hydrolysates of commercial bovine, porcine, and tilapia gelatins using bioinformatics in combination with in vitro and in vivo studies. The hydrolysate with superior inhibition of angiotensin converting enzyme (ACE) activity was used to treat the D-galactose (DG)-induced amnesic mice. In silico digestion of the gelatins led to the identification of peptide sequences with potential antioxidant, ACE-inhibitory, and anti-amnestic properties. The results of in vitro digestion revealed that the <1 kDa peptide fraction of porcine gelatin hydrolysate obtained after 1 h digestion with papain (PP) (PP1, <1 kDa) potently inhibited ACE, acetylcholinesterase, and prolyl endopeptidase activities at 87.42%, 21.24%, and 48.07%, respectively. Administering the PP1 to DG-induced amnesic mice ameliorated the spatial cognitive impairment and Morris water maze learning abilities. The dentate area morphology in the PP1-treated mice was relatively similar to the control group. In addition, PP1 enhanced the antioxidant capacity in the DG-induced amnesic mice. This study suggests that PP1 could serve as a potential treatment tool against oxidative stress, hypertension, and neurodegenerative diseases.

The Structure of Maltooctaose-Bound Escherichia coli Branching Enzyme Suggests a Mechanism for Donor Chain Specificity.

Glycogen is the primary storage polysaccharide in bacteria and animals. It is a glucose polymer linked by α-1,4 glucose linkages and branched via α-1,6-linkages, with the latter reaction catalyzed by branching enzymes. Both the length and dispensation of these branches are critical in defining the structure, density, and relative bioavailability of the storage polysaccharide. Key to this is the specificity of branching enzymes because they define branch length. Herein, we report the crystal structure of the maltooctaose-bound branching enzyme from the enterobacteria E. coli. The structure identifies three new malto-oligosaccharide binding sites and confirms oligosaccharide binding in seven others, bringing the total number of oligosaccharide binding sites to twelve. In addition, the structure shows distinctly different binding in previously identified site I, with a substantially longer glucan chain ordered in the binding site. Using the donor oligosaccharide chain-bound Cyanothece branching enzyme structure as a guide, binding site I was identified as the likely binding surface for the extended donor chains that the E. coli branching enzyme is known to transfer. Furthermore, the structure suggests that analogous loops in branching enzymes from a diversity of organisms are responsible for branch chain length specificity. Together, these results suggest a possible mechanism for transfer chain specificity involving some of these surface binding sites.

Incidence and prevalence of immune thrombocytopenia under the copayment waiver policy for pediatric patients in Korea: Data from the National Health Claims Database.

The purpose of this study was to investigate the epidemiology of immune thrombocytopenia (ITP) under the copayment waiver policy for pediatric patients in Korea. The data were collected from the National Health Insurance Claims Database of Korea. ITP was identified based on the diagnostic code D69.38 from the Korean Standard Classification of Diseases. Patients between one and 18 years old, who had at least one health insurance claim for ITP as a final diagnosis, from 1 January 2016, to 31 December 2017, were analyzed. Prevalent cases were defined as patients who used, at least one time, any medical services coded as D69.38. Incident cases were defined as patients who did not use D69.38 coded medical services during the prior year and were newly registered in 2017. The prevalence and incidence of ITP were 24.53 and 13.39 per 100,000 persons. The peak rates were observed in 1-year-old patients. The gender-specific prevalence of ITP was significantly higher in one-year-old males than females. According to the change-point analysis, we found that the prevalence and incidence diminished rapidly at the ages of four and three, respectively. This Korean population-based epidemiological study of ITP provided meaningful insights into the current epidemiology of ITP and demonstrated the implications of interpreting epidemiologic studies to reflect age categorizing and health care system characteristics.

Electrical Properties of the Carbon-Nanotube Composites Film Under Extreme Temperature Condition.

Carbon nanotube (CNT) composites have been widely investigated for electric heating applications (such as water heater, de-icing unit, and patternable micro heaters) owing to their rapid heating, flexibility and light-weight properties. For practical use of CNT composite as heating element applications, the change of resistance with varying temperature must be interpreted. In this study, electric heating behavior of CNT/Nylon 6 composite film (10 wt%) and CNT/Polydimethylsiloxane (PDMS) composite film (10 wt%) were evaluated by measuring the change in normalized resistance under extreme temperature from -50 °C to 100 °C. While CNT/PDMS composite film showed 25% normalized resistance change from -50 °C to 100 °C, in the case of CNT/Nylon 6 composite film, only 10% normalized resistance change was shown. The difference of resistance change is attributed to the difference of the polymer's coefficient of thermal expansion (CTE), which is a crucial factor to consider in the design of CNT composites as a heater or heating sensor. CNT/Nylon 6 composite film is appropriate for flexible heating unit and de-icing application, due to the lower degree of resistance change than that of CNT/PDMS composite film. In addition, a thermal cycling test was conducted to determine the thermal stability and repeatability of CNT composites.

Conducting Super-Hydrophobic Thin Film for Electric Heating Applications.

Frost presents a serious problem for the human environment, resulting in such phenomena as downed power lines, damaged crops and stalled aircraft. In addition, frost and ice accumulation significantly decrease the performance of ships, wind turbines, and HVAC systems with high failure risk. Super-hydrophobic (SH) surface can be an appropriate solution for frost problems, due to its anti-icing properties that can prevent ice nucleation on the surface. In addition, in the case of conducting SH surface using carbon nanotubes (CNTs) as a filler, it can form an excellent heating unit, owing to the resistive heating effect. The purpose of this study is to produce a large-area conducting SH film that can prevent ice nucleus and remove ice formation rapidly. High aspect ratio carbon nanotubes (CNTs) as a conducting filler and adhesive polymer resin as a binder were used to form coating layer. In addition, silica particles (~7 nm) were used to stabilize nano-size roughness of the SH surface. Wet and dry etching processes were used on the substrate to improve wettability and to produce organic functional groups. To evaluate the de-icing effect, the fabricated SH surface was rapidly heated to 150 °C by applying voltage.

Effect of tumour necrosis factor-alpha inhibitors on renal function in patients with rheumatoid arthritis from the KOBIO registry from 2012 to 2016.

OBJECTIVES: The effect of biological disease-modifying anti-rheumatic drugs (bDMARDs) on renal function in patients with rheumatoid arthritis (RA) has not been well established. We assessed whether tumour necrosis factor (TNF) inhibitors could affect renal function in RA. METHODS: A total of 2110 patients with RA enrolled in the Korean College of Rheumatology Biologics (KOBIO) registry were analysed. All patients were taking bDMARDs or conventional synthetic DMARDs (csDMARDs). Renal function was evaluated by calculating the estimated glomerular filter rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation. Renal insufficiency was defined as eGFR <60 mL/min/1.73 m2. Differences in eGFR changes between different types of DMARDs were assessed at each follow-up time using the generalised linear model (GLM) method. Risk factors for renal insufficiency were identified using binary logistic regression analysis. RESULTS: The changes of eGFR values in patients treated with TNF inhibitors were not significantly different from those with csDMARDs alone or non-TNF inhibitors in all RA patients regardless of renal function. Among patients with renal insufficiency, GLM analysis revealed that the changes of eGFR values by TNF inhibitors were also compatible to those treated with csDMARDs alone or non-TNF inhibitors. Older age (>55 years), longer disease duration (>5 years), and use of methotrexate were identified as clinical determinants for renal insufficiency. CONCLUSIONS: TNF inhibitors did not influence the change of renal function during RA treatment. TNF inhibitors may be a safe treatment option irrespective of renal function.

Nanotube and poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) composite film for the electrode applications in organic thin-film transistor and dye-sensitized solar cells.

In this study, composite films made of coiled carbon nanotubes (CCNTs) and poly(3,4-ethylenedioxythiophene) polymerized with poly(4-styrenesulfonate) (PEDOT:PSS) were fabricated with different composition ratios. The variations in film properties (including surface morphology, work function, and electrical conductivity) in accordance with the amount of CCNT dosing were investigated. Subsequently, through HCl-methanol treatment, we achieved a significant enhancement in electrical conductivity with little damage to the CCNT features. The characteristics of CCNT/PEDOT:PSS composite film are generally comparable to those of PEDOT:PSS film, and some of them, such as catalytic activity and work function, are significantly higher. On the basis of these versatile features, the CCNT/PEDOT:PSS composite films exhibit excellent performance as source/drain electrode in organic thin-film transistors and as catalytic counter electrode in dye-sensitized solar cells.

Discovery of Nicotinamide Adenine Dinucleotide Binding Proteins in the Escherichia coli Proteome Using a Combined Energetic- and Structural-Bioinformatics-Based Approach.

Protein-ligand interaction plays a critical role in regulating the biochemical functions of proteins. Discovering protein targets for ligands is vital to new drug development. Here, we present a strategy that combines experimental and computational approaches to identify ligand-binding proteins in a proteomic scale. For the experimental part, we coupled pulse proteolysis with filter-assisted sample preparation (FASP) and quantitative mass spectrometry. Under denaturing conditions, ligand binding affected protein stability, which resulted in altered protein abundance after pulse proteolysis. For the computational part, we used the software Patch-Surfer2.0. We applied the integrated approach to identify nicotinamide adenine dinucleotide (NAD)-binding proteins in the Escherichia coli proteome, which has over 4200 proteins. Pulse proteolysis and Patch-Surfer2.0 identified 78 and 36 potential NAD-binding proteins, respectively, including 12 proteins that were consistently detected by the two approaches. Interestingly, the 12 proteins included 8 that are not previously known as NAD binders. Further validation of these eight proteins showed that their binding affinities to NAD computed by AutoDock Vina are higher than their cognate ligands and also that their protein ratios in the pulse proteolysis are consistent with known NAD-binding proteins. These results strongly suggest that these eight proteins are indeed newly identified NAD binders.

Catalytic Pyrolysis of Cork Oak Over Supercritical Hydrothermal Synthesized Nanosized ZrO2.

The change in acidity of pyrolysis bio-oil was investigated using the catalytic pyrolysis of cork oak over zirconia synthesized by supercritical hydrothermal synthesis using a fixed bed reactor. Catalytic pyrolysis over zirconia reduced the content of acetic acid considerably and showed high selectivity to ketones and high-value-added aromatic compounds.

Prevalence and incidence of gout in Korea: data from the national health claims database 2007-2015.

The purpose of the present study was to investigate the prevalence and incidence of gout in Korea and predict the future prevalence and incidence of gout. Data were collected from the national health claims database. Patients who had at least one claim for gout between 2007 and 2015 were included in the study. The prevalence of gout from 2007 to 2015 and the incidence of gout from 2009 to 2015 were determined. We estimated sex- and age-specific prevalence and incidence of gout during the period. The prevalence and incidence of gout were predicted using time series analysis. The prevalence of gout (95% CI) increased from 3.49 (3.48-3.51) per 1000 persons in 2007 to 7.58 (7.55-7.60) per 1000 persons in 2015. The incidence of gout (95% CI) was 1.52 (1.51-1.53) in 2009 and rose to 1.94 (1.93-1.95) per 1000 persons in 2015. The prevalence and incidence of gout were higher in men than in women. The older population had a higher prevalence and incidence than the younger population. The increase in prevalence was higher in the older population than the younger population, whereas the increase in incidence was higher in the younger population than the older population. The predicted prevalence and incidence of gout (95% CI) in 2025 were 16.59 (15.85-17.34) per 1000 persons and 3.81 (3.14-4.47) per 1000 persons. The prevalence and incidence of gout increased in Korea between 2007 and 2015. Men and the older population had a higher prevalence and incidence of gout compared to women and the younger population. However, the incidence of gout in the younger population has increased rapidly in recent years.

What factors affect discordance between physicians and patients in the global assessment of disease activity in rheumatoid arthritis?

OBJECTIVE: To identify the level of agreement between patients with rheumatoid arthritis (RA) and physicians in the global assessment of disease activity and to explore factors influencing their discordance. METHODS: A total of 4368 patients with RA were analyzed from the KORean Observational study Network for Arthritis (KORONA) database. Patients were divided into four subgroups according to difference from their physicians in the assessment of disease activity by substracting physician's visual analog scale (VAS) from patient's VAS as follows: positive discordance group I (10 mm ≤ discordance <25 mm), positive discordance group II (≥25 mm), concordance (<|10| mm), and negative discordance (≤ -10mm). Multinomial logistic regression analysis was performed to identify factors associated with discordance. RESULTS: Only 1350 (29.2%) patients were classified in the concordance group. Positive discordance was found in 52.3% of the patients (n = 2425), with 33.7% (n = 1563) showing marked discordance (≥25 mm). The high disease activity (OR =1.41), gastrointestinal (GI) disease (OR =1.28), pain (OR =1.12), fatigue (OR =1.07) were consistently associated with positive discordance. CONCLUSION: More than half of patients with RA thought their disease more severe than their physicians. In addition to high disease activity, pain, fatigue, and sleep disturbance or GI disease were associated with the discordance between physicians and patients with RA.

Dysregulation of Norepinephrine Release in the Absence of Functional Synaptotagmin 7.

Synaptotagmin 7 (Syt7) is expressed in cardiac sympathetic nerve terminals where norepinephrine (NE) is released in both Ca(2+)-dependent exocytosis and Ca(2+)-independent norepinephrine transporter (NET)-mediated overflow. The role of Syt7 in the regulation of NE release from cardiac sympathetic nerve terminals is tested by employing a Syt7 knock-in mouse line that expresses a non-functional mutant form of Syt7. In cardiac sympathetic nerve terminals prepared from these Syt7 knock-in mice, the Ca(2+)-dependent component of NE release was diminished. However, these terminals displayed upregulated function of NET (∼130% of controls) and a significant increase in Ca(2+)-independent NE overflow (∼140% of controls), which is greater than the Ca(2+)-dependent component of NE exocytosis occurring in wild-type controls. Consistent with a significant increase in NE overflow, the Syt7 knock-in mice showed significantly higher blood pressures compared to those of littermate wild-type and heterozygous mice. Our results indicate that the lack of functional Syt7 dysregulates NE release from cardiac sympathetic nerve terminals.

Catalytic Reforming of Lignin-Derived Bio-Oil Over a Nanoporous Molecular Sieve Silicoaluminophosphate-11.

Catalytic pyrolysis of lignin, a major constituent of biomass, was performed. A nanoporous molecular sieve silicoaluminophosphate-11 (SAPO-11) was selected as catalyst. Thermogravimetric analysis showed that 500 degrees C was the optimal pyrolysis temperature. Pyrolyzer-gas chromatography/mass spectroscopy was used to investigate the pyrolysis product distribution. Production of phenolics, the dominant product from the pyrolysis of lignin, was promoted by the increase in the catalyst dose. In particular, low-molecular-mass phenolics were produced more over SAPO-11, while high-molecular-mass phenolics and double-bond-containing phenolics were produced less. The fraction of aromatic compounds, including benzene, toluene, xylene, and ethylbenzene, was also increased by catalytic reforming. The catalytic effects were more pronounced when the catalyst/biomass ratio was increased. The enhanced production of aromatic compounds by an acidic catalyst obtained in this study is in good agreement with the results of previous studies.

Mapping health assessment questionnaire disability index (HAQ-DI) score, pain visual analog scale (VAS), and disease activity score in 28 joints (DAS28) onto the EuroQol-5D (EQ-5D) utility score with the KORean Observational study Network for Arthritis (KORONA) registry data.

The aim of this study was to estimate the mapping model for EuroQol-5D (EQ-5D) utility values using the health assessment questionnaire disability index (HAQ-DI), pain visual analog scale (VAS), and disease activity score in 28 joints (DAS28) in a large, nationwide cohort of rheumatoid arthritis (RA) patients in Korea. The KORean Observational study Network for Arthritis (KORONA) registry data on 3557 patients with RA were used. Data were randomly divided into a modeling set (80 % of the data) and a validation set (20 % of the data). The ordinary least squares (OLS), Tobit, and two-part model methods were employed to construct a model to map to the EQ-5D index. Using a combination of HAQ-DI, pain VAS, and DAS28, four model versions were examined. To evaluate the predictive accuracy of the models, the root-mean-square error (RMSE) and mean absolute error (MAE) were calculated using the validation dataset. A model that included HAQ-DI, pain VAS, and DAS28 produced the highest adjusted R (2) as well as the lowest Akaike information criterion, RMSE, and MAE, regardless of the statistical methods used in modeling set. The mapping equation of the OLS method is given as EQ-5D = 0.95-0.21 × HAQ-DI-0.24 × pain VAS/100-0.01 × DAS28 (adjusted R (2) = 57.6 %, RMSE = 0.1654 and MAE = 0.1222). Also in the validation set, the RMSE and MAE were shown to be the smallest. The model with HAQ-DI, pain VAS, and DAS28 showed the best performance, and this mapping model enabled the estimation of an EQ-5D value for RA patients in whom utility values have not been measured.

Factors Contributing to Discordance between the 2011 ACR/EULAR Criteria and Physician Clinical Judgment for the Identification of Remission in Patients with Rheumatoid Arthritis.

Remission is a primary end point of in clinical practice and trials of treatments for rheumatoid arthritis (RA). The 2011 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria were developed to provide a consensus definition of remission. This study aimed to assess the concordance between the new remission criteria and the physician's clinical judgment of remission and also to identify factors that affect the discordance between these two approaches. A total of 3,209 patients with RA were included from the KORean Observational Study Network for Arthritis (KORONA) database. The frequency of remission was evaluated based on each approach. The agreement between the results was estimated by Cohen's kappa (κ). Patients with remission according to the 2011 ACR/EULAR criteria (i.e. the Boolean criteria) and/or physician judgment (n = 855) were divided into three groups: concordant remission, the Boolean criteria only, and physician judgment only. Multinomial logistic regression analysis was used to identify factors responsible for the assignment of patients with remission to one of the discordant groups rather than the concordant group. The remission rates using the Boolean criteria and physician judgment were 10.5% and 19.9%, respectively. The agreement between two approaches for remission was low (κ = 0.226) and the concordant remission rate was only 5.5% (n = 177). Pain affected classification in both discordant groups, whereas fatigue was associated with remission only by physician clinical judgment. The Boolean criteria were more stringent than clinical judgment. Patient subjective symptoms such as pain and fatigue were associated with discordance between the two approaches.

Preparation and Characterization of Cobalt/Graphene Composites Using Liquid Phase Plasma System.

Liquid phase plasma (LPP) method was applied, for the first time, to the impregnation of cabalt nanoparticles onto graphene. Nanoparticles were dispersed uniformly on the surface of the two-dimensional graphene sheet. The electron miocroscopy observation showed approximately 2-7 nm sized spherical nanoparticles deposited on the surface of graphene sheets. The XPS and EDX analyses revealed that both metal Co and CoO were present in the Co/graphene composites synthesized by the LPP method.

Hydrodeoxygenation of Guaiacol Over Pt/Al-SBA-15 Catalysts.

Upgrading of bio-oil through catalytic hydrodeoxygenation (HDO) reaction was investigated for guaiacol as a model compound. A batch reactor was used for the reaction condition of 40 bar and 250 degrees C. The target product was cyclohexane. Pt/Al-SBA-15 with the Si/Al ratios of 20, 40, and 80 and Pt/HZSM-5 were used as the catalyst. The SBA-15 catalysts were characterized by N2 adsorption-desorption, X-ray diffraction analysis, and temperature programmed desorption of ammonia. The order of cyclohexane yield was Pt/Al-SBA-15 (Si/Al = 20) > Pt/Al-SBA-15(40) > Pt/Al-SBA-15 (80), indicating that the quantity of acid sites plays an important role in the HDO reaction. On the other hand, Pt/HZSM-5 led to a very low cyclohexane yield, in spite of its abundant strong acid sites, due to its small pore size.

Preparation and Characterization of Low Molecular Weight Heparin by Liquid Phase Plasma Method.

An liquid phase plasma process system was applied to the production of low molecular weight heparin. The molecular weight of produed heparin decreased with increasing liquid phase plasma treatment time. The abscission of the chemical bonds between the constituents of heparin by liquid phase plasma reaction did not alter the characteristics of heparin. Formation of any by-products due to side reaction was not observed. It is suggested that heparin was depolymerized by active oxygen radicals produced during the liquid phase plasma reaction.