Risk of New-Onset Acute Coronary Syndrome and Atrial Fibrillation in Patients With Rheumatoid Arthritis Compared With a Risk-Set and Propensity Score-Matched Cohort　- A Nationwide Cohort Study.

BACKGROUND: Rheumatoid arthritis (RA) has extra-articular manifestations of cardiovascular diseases and is associated with a high mortality rate in Western populations. This study aimed to investigate the risk of acute coronary syndrome (ACS) and atrial fibrillation (AF) associated with RA in a Korean population.Methods and Results:Patients were selected from a senior cohort from the Korean National Health Insurance Service in 2002, and followed until 31 December 2015. Patients with newly developed ACS and AF were identified and compared with controls for a 10-year period using time-dependent propensity and risk-set matching. A total of 4,217 incident RA patients and their 8,432 controls comprised the incident RA and matched cohorts, respectively. ACS was identified during 24,642 person-years [incidence rate (IR) 402 per 10,000 person-years, 95% confidence interval (CI) 330-489] among the RA cohort. In the matched cohort, 141 ACS patients were identified during 50,011 person-years (IR 282 per 100,000 person-years, 95% CI 239-333). RA patients were 1.43-fold more likely to develop ACS than the matched controls [hazard ratio (HR) 1.43, 95% CI 1.10-1.84], but showed similar occurrence risk of AF (HR 1.06, 95% CI 0.83-1.35). CONCLUSIONS: A higher risk for ACS and a similar risk for AF were found by risk-set matched analysis in a senior RA cohort compared with the control, using Korean nationwide long-term data.

Analysis of multidimensional factors in attempts to quit using tobacco by Korean adolescents.

BACKGROUND: This study aims to understand the extent of adolescents' attempts to quit using tobacco and the factors influencing such attempts in Korea, using a descriptive, cross-sectional design and secondary data analysis with the 2019 Youth Health Behavior Survey. METHODS: The participants were 4028 adolescent tobacco users who had used tobacco for 1 day or more in the past 30 days. The data analysis was performed using IBM SPSS/WIN 26.0 program, and multivariable logistic regression analysis was conducted using the complex sampling method module. RESULTS: A total of 68.2% of the participants attempted to quit using tobacco. We analyzed the factors for adolescents' attempts to quit using tobacco by dividing them into psychological, physical, behavioral, and environmental dimensions. The factors influencing adolescents' attempts to quit using tobacco, identified through multivariable logistic regression analysis, are as follows: participation in sports activities (OR = 1.20, 95% CI 1.01-1.41), vigorous physical activity (OR = 1.24, 95% CI 1.06-1.46), and type of tobacco product used (OR = 1.65, 95% CI 1.24-2.21) in the behavioral dimension; pictorial cigarette pack warnings (perceived smoking as unhealthy) (OR = 1.91, 95% CI 1.56-2.36), and the presence of secondhand smoking at home (OR = 1.18, 95% CI 1.01-1.38) in the environmental dimension. CONCLUSIONS: Schools and public healthcare providers must consider multidimensional factors when providing support for successful tobacco cessation in adolescents and focus particularly on elements relating to physical activity and environmental factors.

Biokinetics of food additive silica nanoparticles and their interactions with food components.

Nanomaterials have been widely utilized in the food industry in production, packaging, sensors, nutrient delivery systems, and food additives. However, research on the interactions between food-grade nanoparticles and biomolecules as well as their potential toxicity is limited. In the present study, the in vivo solubility, oral absorption, tissue distribution, and excretion kinetics of one of the most extensively used food additives, silica (SiO2) were evaluated with respect to particle size (nano vs bulk) following single-dose oral administration to rats. Intestinal transport mechanism was investigated using a 3D culture system, in vitro model of human intestinal follicle-associated epithelium (FAE). The effect of the presence of food components, such as sugar and protein, on the oral absorption of nanoparticles was also evaluated with focus on their interactions. The results obtained demonstrated that the oral absorption of nanoparticles (3.94±0.38%) was greater than that of bulk materials (2.95±0.37%), possibly due to intestinal transport by microfold (M) cells. On the other hand, particle size was found to have no significant effect on in vivo dissolution property, biodistribution, or excretion kinetics. Oral absorption profile of silica nanoparticles was highly dependent on the presence of sugar or protein, showing rapid absorption rate in glucose, presumably due to their surface interaction on nanoparticles. These findings will be useful for predicting the potential toxicity of food-grade nanoparticles and for understanding biological interactions.

Bioavailability of Silica, Titanium Dioxide, and Zinc Oxide Nanoparticles in Rats.

Inorganic nanoparticles have been widely applied to various industrial fields and biological applications. However, the question as to whether nanoparticles are more efficiently absorbed into the systemic circulation than bulk-sized materials remains to be unclear. In the present study, the physico-chemical and dissolution properties of the most extensively developed inorganic nanoparticles, such as silica (SiO2), titanium dioxide (TiO2), and zinc oxide (ZnO), were analyzed, as compared with bulk-sized particles. Furthermore, the bioavailability of nanoparticles versus their bulk counterparts was evaluated in rats after a single oral administration and intravenous injection, respectively. The results demonstrated that all bulk materials had slightly higher crystallinity than nanoparticles, however, their dissolution properties were not affected by particle size. No significant difference in oral absorption and bioavailability of both SiO2 and TiO2 was found between nano- and bulk-sized materials, while bulk ZnO particles were more bioavailable in the body than ZnO nanoparticles. These finding will provide critical information to apply nanoparticles with high efficiency as well as to predict their toxicity potential.

Titanium Dioxide Nanoparticle-Biomolecule Interactions Influence Oral Absorption.

Titanium dioxide (TiO2) nanoparticles (NPs) have been widely applied in various industrial fields, such as electronics, packaging, food, and cosmetics. Accordingly, concerns about the potential toxicity of TiO2 NPs have increased. In order to comprehend their in vivo behavior and potential toxicity, we must evaluate the interactions between TiO2 NPs and biomolecules, which can alter the physicochemical properties and the fate of NPs under physiological conditions. In the present study, in vivo solubility, oral absorption, tissue distribution, and excretion kinetics of food grade TiO2 (f-TiO2) NPs were evaluated following a single-dose oral administration to rats and were compared to those of general grade TiO2 (g-TiO2) NPs. The effect of the interactions between the TiO2 NPs and biomolecules, such as glucose and albumin, on oral absorption was also investigated, with the aim of determining the surface interactions between them. The intestinal transport pathway was also assessed using 3-dimensional culture systems. The results demonstrate that slightly higher oral absorption of f-TiO2 NPs compared to g-TiO2 NPs could be related to their intestinal transport mechanism by microfold (M) cells, however, most of the NPs were eliminated through the feces. Moreover, the biokinetics of f-TiO2 NPs was highly dependent on their interaction with biomolecules, and the dispersibility was affected by modified surface chemistry.

Inactivation of the virulence factors from 2,3-butanediol-producing Klebsiella pneumoniae.

The microbiological production of 2,3-butanediol (2,3-BDO) has attracted considerable attention as an alternative way to produce high-value chemicals from renewable sources. Among the number of 2,3-BDO-producing microorganisms, Klebsiella pneumoniae has been studied most extensively and is known to produce large quantity of 2,3-BDO from a range of substrates. On the other hand, the pathogenic characteristics of the bacteria have limited its industrial applications. In this study, two major virulence traits, outer core LPS and fimbriae, were removed through homologous recombination from 2,3-BDO-producing K. pneumoniae 2242 to expand its uses to the industrial scale. The K. pneumoniae 2242 ∆wabG mutant strain was found to have an impaired capsule, which significantly reduced its ability to bind to the mucous layer and evade the phagocytic activity of macrophage. The association with the human ileocecal epithelial cell, HCT-8, and the bladder epithelial cell, T-24, was also reduced dramatically in the K. pneumoniae 2242 ∆fimA mutant strain that was devoid of fimbriae. However, the growth rate and production yield for 2,3-BDO were unaffected. The K. pneumoniae strains developed in this study, which are devoid of the major virulence factors, have a high potential for the efficient and sustainable production of 2,3-BDO.

Toxicity and Biokinetics of Colloidal Gold Nanoparticles.

Gold nanoparticles (Au-NPs) have promising potential for diverse biological application, but it has not been completely determined whether Au-NP has potential toxicity in vitro and in vivo. In the present study, toxicity of Au-NP was evaluated in human intestinal cells as well as in rats after 14-day repeated oral administration. Biokinetic study was also performed to assess oral absorption and tissue distribution. The results demonstrated that Au-NP did not cause cytotoxic effects on cells after 24 h exposure in terms of inhibition of cell proliferation, membrane damage, and oxidative stress. However, when a small number of cells were exposed to Au-NP for seven days, colony forming ability remarkably decreased by Au-NP treatment, suggesting its potential toxicity after long-term exposure at high concentration. Biokinetic study revealed that Au-NP slowly entered the blood stream and slightly accumulated only in kidney after oral administration to rats. Whereas, orally administered Au ions were rapidly absorbed, and then distributed in kidney, liver, lung, and spleen at high levels, suggesting that the biological fate of Au-NP is primarily in nanoparticulate form, not in ionic Au. Fourteen-day repeated oral toxicity evaluation showed that Au-NP did not cause severe toxicity in rats based on histopathological, hematological, and serum biochemical analysis.

Cytotoxicity, Uptake Behaviors, and Oral Absorption of Food Grade Calcium Carbonate Nanomaterials.

Calcium is the most abundant mineral in human body and essential for the formation and maintenance of bones and teeth as well as diverse cellular functions. Calcium carbonate (CaCO3) is widely used as a dietary supplement; however, oral absorption efficiency of CaCO3 is extremely low, which may be overcome by applying nano-sized materials. In this study, we evaluated the efficacy of food grade nano CaCO3 in comparison with that of bulk- or reagent grade nano CaCO3 in terms of cytotoxicity, cellular uptake, intestinal transport, and oral absorption. Cytotoxicity results demonstrated that nano-sized CaCO3 particles were slightly more toxic than bulk materials in terms of oxidative stress and membrane damage. Cellular uptake behaviors of CaCO3 nanoparticles were different from bulk CaCO3 or Ca2+ ions in human intestinal epithelial cells, showing efficient cellular internalization and elevated intracellular Ca2+ levels. Meanwhile, CaCO3 nanoparticles were efficiently transported by microfold (M) cells in vitro model of human intestinal follicle-associated epithelium, in a similar manner as Ca2+ ions did. Biokinetic study revealed that the biological fate of CaCO3 particles was different from Ca2+ ions; however, in vivo, its oral absorption was not significantly affected by particle size. These findings provide crucial information to understand and predict potential toxicity and oral absorption efficiency of food grade nanoparticles.