BMI trajectory and inflammatory effects on metabolic syndrome in adolescents.

BACKGROUND: Various life course factors can affect susceptibility to diseases during adolescence and adulthood, and those relationships are complex. However, few studies have assessed the potential mediating factors. Therefore, we assessed the mediating effects of factors related to growth and inflammation between perinatal factors and metabolic syndrome risk during adolescence. METHODS: The study was conducted on adolescents who participated in the follow-up in the Ewha Birth and Growth Cohort. We considered the ponderal index (PI) as a perinatal factor and the continuous metabolic syndrome score (cMetS) as the outcome and confirmed the mediating effects of body mass index (BMI) trajectory pattern in childhood and inflammation levels by using the PROCESS macro for SAS. RESULTS: Although the direct effect of BMI trajectory on the relationship between PI and cMetS was not significant (0.545), the indirect effect was significant (1.044). In addition, the indirect effect was statistically significant in the pathways mediating the BMI trajectory pattern and inflammation (ß = 1.456). CONCLUSIONS: The direct and indirect effects on the relationship between PI and cMetS suggest that childhood factors related to growth may be involved in disease susceptibility. Therefore, appropriate interventions for the management of obesity during the growth phase are necessary. IMPACT: Unlike other existing studies, this study assessed multiple mediating effects by considering the BMI trajectory pattern and inflammatory indexes as mediating factors between the ponderal index and the continuous metabolic syndrome score during adolescence. We found significant indirect effects of the BMI trajectory between PI and cMetS, and also significant indirect effects in the pathways mediating the BMI trajectory and hs-CRP. The significant indirect mediating effects support that childhood factors related to growth may be involved in disease susceptibility.

The effect of biological agent on body composition in patients with Crohn's disease.

BACKGROUND: Crohn's disease (CD) is associated with altered body composition, affecting clinical outcomes. We evaluated the impact of biologics on body composition in CD patients. METHODS: This multicenter longitudinal study across four Korean university hospitals conducted from January 2009 to August 2021 retrospectively reviewed data of CD patients with abdominal computed tomography (CT) before and after the biologic treatment. Skeletal muscle area (SMA), visceral fat area (VFA), and subcutaneous fat area (SFA) of the third lumbar vertebra (L3) on CT were measured. Myopenia was defined as L3 skeletal muscle index (SMI) of < 49 and < 31 cm2/m2 for men and women, respectively. RESULTS: Among 112 participants, 79 (70.5%) had myopenia. In the myopenia group, all body composition parameters were significantly increased after the biologic treatment: SMI (37.68 vs. 39.40 cm2/m2; P < 0.001), VFA (26.12 vs. 54.61 cm2; P < 0.001), SFA (44.29 vs. 82.42 cm2; P < 0.001), while no significant differences were observed in the non-myopenia group. In multivariate analysis, penetrating CD (hazard ratio, 5.40; P = 0.020) was the independent prognostic factor for surgery. Operation-free survival rate tended to decrease in the myopenia group (Log-rank test, P = 0.090). CONCLUSIONS: Biological agents can increase all body composition parameters in CD patients with myopenia. These patients are more likely to experience surgery.

The association between urinary cotinine level and metabolic syndrome profiles among adolescents: findings from the Ewha Birth and growth study.

BACKGROUND: Secondhand smoke (SHS) exposure among adolescents who are still developing can negatively affect their physical and psychological health, including metabolic syndrome (MetS), which is a risk factor for cardiovascular disease. However, the relationship between exposure to SHS and MetS in adolescence has not been evaluated. METHODS: A total of 240 subjects aged 13-15 years who were followed up in the Ewha Birth and Growth Study were included in this study. Using the urinary cotinine level, the participants' exposure to SHS was divided into tertiles, and the continuous MetS score (cMetS) and its components were compared among the three groups using a generalized linear model and trend analysis. Univariate and multivariate linear regression analyses were performed. We adjusted for several confounding variables including sex, father's education level, father's current alcohol consumption status, moderate physical activity, and overweight status. RESULTS: The association between cMetS and the urinary cotinine level was not significant. However, the higher the urinary cotinine level, the lower the high-density lipoprotein cholesterol (HDL-C) level. In particular, the significance of the HDL-C level was maintained after adjusting for covariates. CONCLUSIONS: This study supports an association between SHS exposure and the components of MetS in adolescents aged 13-15 years, and it suggests the need to address SHS exposure in adolescents to reduce the cardiovascular risk in later life.

Understanding the Role of M13 Bacteriophage Thin Films on a Metallic Nanostructure through a Standard and Dynamic Model.

The dynamic and surface manipulation of the M13 bacteriophage via the meeting application demands the creation of a pathway to design efficient applications with high selectivity and responsivity rates. Here, we report the role of the M13 bacteriophage thin film layer that is deposited on an optical nanostructure involving gold nanoparticles/SiO2/Si, as well as its influence on optical and geometrical properties. The thickness of the M13 bacteriophage layer was controlled by varying either the concentration or humidity exposure levels, and optical studies were conducted. We designed a standard and dynamic model based upon three-dimensional finite-difference time-domain (3D FDTD) simulations that distinguished the respective necessity of each model under variable conditions. As seen in the experiments, the origin of respective peak wavelength positions was addressed in detail with the help of simulations. The importance of the dynamic model was noted when humidity-based experiments were conducted. Upon introducing varied humidity levels, the dynamic model predicted changes in plasmonic properties as a function of changes in NP positioning, gap size, and effective index (this approach agreed with the experiments and simulated results). We believe that this work will provide fundamental insight into understanding and interpreting the geometrical and optical properties of the nanostructures that involve the M13 bacteriophage. By combining such significant plasmonic properties with the numerous benefits of M13 bacteriophage (like low-cost fabrication, multi-wavelength optical characteristics devised from a single structure, reproducibility, reversible characteristics, and surface modification to suit application requirements), it is possible to develop highly efficient integrated plasmonic biomaterial-based sensor nanostructures.

Health and Mortality in Korean Healthcare Workers.

BACKGROUND: To evaluate the health status of healthcare workers (doctors and nurses) compared to those in the general population based on the National Health Insurance Service database and the cause of death data from Statistics Korea. METHODS: The subjects of this study were 104,484 doctors and 220,310 nurses working in healthcare facilities from 2002 to 2017, and who had undergone at least one general medical examination. Based on the subject definition, the subject data were extracted from the National Health Insurance healthcare facility database and qualification database. We collected medical use details included in the research database, general medical examination results, medical history included in the health examination database, and additional data on the cause of death from the National Statistics database to analyze the main cause of death and mortality. RESULTS: In terms of the major causes of death and mortality among healthcare workers, the mortality rate associated with intentional self-harm, injury, transportation accident, heart disease, addiction, and falling was significantly higher than that in the general population. Further, the prevalence of respiratory and gastrointestinal diseases was high. When analyzing the proportional mortality ratio (PMR) by cause of death for healthcare workers, the PMR values for death related to malignant neoplasm was the highest. In terms of diseases, both doctors and nurses had higher rates of infectious diseases such as maternal sepsis, rubella, and measles. CONCLUSION: The health status of healthcare workers differs from that of the general population. Thus, it is important to consider the occupational characteristics of healthcare personnel. This study is unique in that it was conducted based on medical use indicators rather than survey data.

Joinpoint Regression About Injury Mortality and Hospitalization in Korea.

BACKGROUND: Injury is a social problem that causes health and property losses, and it is important to identify the size and trend of injury for efficient prevention and management. Therefore, this study analyzed the trends in injury mortality and hospitalization rates from 2005 to 2019 in Korea. METHODS: Using mortality data by Statistics Korea and Korea National Hospital Discharge In-depth injury survey by the Korea Disease Control and Prevention Agency (KDCA), age standardized rates were calculated for death and hospitalization to analyze trends and annual changes with the joinpoint regression model. In addition, annual changes in the hospitalization rate of the transport accident and fall injuries by age group were analyzed, which are the major causes of injuries. RESULTS: From 2005 to 2019, the injury mortality rate has been on the decline, but the injury hospitalization rate has been on the rise. The annual rate of change varied depending on the injury mechanism, but the mortality rate tended to decrease or remain similar level, while the rate of hospitalization has steadily increased. In addition, by age group, injury mortality and hospitalization rates were high in the elderly. In particular, the hospitalization rate of the elderly was higher when comparing the hospitalization rate of the children in transport accidents and falls. Pedestrian transport accidents tended to decrease under the age of 15, but remained similar for those aged 65 and older, and bicycle accidents tended to increase in both groups. In addition, hospitalization rates were higher in the fall, with both groups showing a statistically significant increase in hospitalization rates caused by falls. CONCLUSION: This study analyzed the trend of injury mortality and hospitalization and found that transport accidents and falls may vary depending on the means or age of the accident. Since injury is a big social problem that is a burden of disease, safety education and legal sanctions for injury prevention should be further improved in the future, especially by prioritizing vulnerable groups by age and detailed mechanisms of injury.

Relationship between multidimensional stressors and quality of life in people with stroke.

This study explored the impact of intrapersonal (stroke severity, physical dysfunction, and fear of stroke recurrence), interpersonal (loneliness), and extrapersonal (economic status) stressors on the quality of life of people with stroke. A correlational cross-sectional research design was employed. This study was based on Betty Neuman's systems theory. One hundred thirty-nine people with stroke were recruited from 10 hospitals in South Korea. Data were collected from January to February 2020 using a structured questionnaire. Data were analyzed using descriptive statistics, independent t-test, one-way analysis of variance, Scheffé test, Pearson's correlation coefficients, Spearman's correlation coefficients, and hierarchical multiple regression analysis. Stroke severity had the strongest association with quality of life among people with stroke, followed by loneliness and fear of stroke recurrence. These variables accounted for approximately 77% of the variance in the quality of life. Stroke severity, loneliness, and fear of stroke recurrence should be systematically monitored to enhance the quality of life in people with stroke. Additionally, a detailed intervention that considers all these stressors must be developed, and its effectiveness must be verified through further research.

Meaning and Status of Health-related Quality of Life Recognized by Medical Professionals: a Qualitative Study.

BACKGROUND: Medical professionals must maintain their health to provide quality medical care to patients safely. However, the health-related quality of life of medical professionals is a complex issue that currently lacks a standardized evaluation approach. Therefore, the purpose of this study was to identify their perceptions of the health-related quality of life of medical professionals and explore ways to measure their quality of life as accurately. METHODS: This study explored the subjective health status and well-being of Korean medical professionals by conducting three focus group discussions (FGDs) with 12 physicians and 6 nurses (November to December 2019). In the FGD, we elicited participants' opinions on existing health-related quality of life measurement tools. Also, we analyzed transcribed data through content analysis. RESULTS: Participants in this study noted the ambiguity in the current definitions of health provided by the World Health Organization. They shared various problems of their health, mainly concerning fatigue and sleep disorders due to their work pattern. Also, participants shared anxiety, burden, and fear of negative consequences due to the complexity of their work. Participants voiced the necessity of a questionnaire on health-related quality of life that reflects the working lives of medical professionals. CONCLUSION: Medical professionals in Korea were mainly criticizing about health-related quality of life problems caused by their work characteristics. The results of this study will provide valuable information for future health-related quality of life surveys targeting medical professionals in Korea, and also help to determine the method for monitoring the health-related quality of life for health professionals. In addition, the aspects and items identified by medical professionals as important for their health-related quality of life may be used as a basis for developing a new health-related quality of life measurement tools for medical professionals.

Gender differences in pharmacokinetics of perfluoropentanoic acid using non-linear mixed-effect modeling in rats.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been used in various industrial applications for many years. Long-chain PFASs are ubiquitous in wildlife and are reported to have a long elimination half-life in biological systems. Moreover, significant gender difference exists in the elimination of PFASs, where less is eliminated in male than in female. Recently, PFASs manufacturers and agencies have tried to replace the use of long-chain PFASs with short-chain PFASs, since they are expected to exhibit less bioaccumulation potential. Nevertheless, the potential risk and the pharmacokinetic (PK) characteristics of the short-chain PFASs still remain unknown. This study aims to fill the knowledge gap on short-chain PFASs, perfluoropentanoic acid (PFPeA), in terms of its PK properties using non-linear mixed-effect modeling and to explore gender differences in rats. Animal studies were carried out following oral or intravenous administration of PFPeA in male and female rats at a dose of 0.5-10 mg/kg. Plasma, urine, feces and nine tissues were collected and analyzed using ultra-performance liquid chromatography-tandem mass spectrometry. PK findings revealed that the clearance and the inter-compartmental clearance were 1.75 and 3.12 times higher in female rats than in male rats, respectively. According to the result, PFPeA is eliminated more rapidly in female rats than in male rats. Also, the tissue distribution study confirmed that distribution characteristics exhibited gender difference. This study provides scientific evidence for conducting further investigation into short-chain PFASs, biomonitoring plans and decision making regarding human health risk assessment.

Disease-Specific Mortality and Prevalence Trends in Korea, 2002-2015.

BACKGROUND: Evaluation of mortality and prevalence trends is important for health planning and priority decision-making in health policy. This study was performed to examine disease-specific mortality and prevalence trends for diseases in Korea from 2002 to 2015. METHODS: In this study, 206 mutually exclusive diseases and injuries were classified into 21 cause clusters, which were divided into three cause groups: 1) communicable, maternal, neonatal, and nutritional conditions; 2) non-communicable diseases (NCDs); and 3) injuries. Cause specific trends for age-standardized mortality and prevalence rates were analyzed by the joinpoint regression method. RESULTS: Between 2002 and 2015, the age-standardized mortality declined to about 177 per 100,000 population, while the age-standardized prevalence rate increased to approximately 68,065 per 100,000 population. Among the 21 cause clusters, most of the disease mortality rates showed decreasing trends. However, neurological disorders, self-harm, and interpersonal violence included periods during which the mortality rates increased in 2002-2015. In addition, the trends for prevalence rates of human immunodeficiency virus infection and acquired immune deficiency syndrome, tuberculosis, transport injuries, and self-harm, and interpersonal violence differed from the overall prevalence rates. The annual percent change in prevalence rates for transport injuries increased during 2004-2007, and then decreased. The self-harm and interpersonal violence prevalence rates decreased from 2004 to 2014. CONCLUSION: Between 2002 and 2015, overall decreasing trends in the mortality rate and increasing trends in the prevalence rate were observed for all causes in Korea. Especially, NCDs represented an important part of the increasing trends in Korea. For clusters of diseases with unusual trends, proper management must be considered.

Blood Pressure Curve for Children Less than 10 Years of Age: Findings from the Ewha Birth and Growth Cohort Study.

BACKGROUND: Routine blood pressure (BP) measurement is recommended to begin at 3 years of age, but there are no national BP reference values for Korean children less than 7 years of age. Therefore, we developed sex-, age-, and height-specific BP reference values for non-overweight children aged 3-9 years. METHODS: We analyzed the data of 416, 340, 321, 323, and 332 subjects aged 3, 5, 7, 8, and 9 years, respectively, who participated in the Ewha Birth and Growth Cohort Study. BP percentile curves were generated using generalized additive models for location, scale, and shape. Reference values for the 50th, 90th, and 95th percentiles of BP were determined according to sex, age, and height percentiles. RESULTS: In both boys and girls, a gradual increase in systolic blood pressure (SBP) with age was more pronounced than that in diastolic blood pressure (DBP). In boys, the reference values for 90th percentile of SBP/DBP at median height for children aged 3 and 9 years were 105/69 and 118/70, respectively. In girls, the reference values corresponding to the above conditions were 105/69 and 116/70, respectively. Among children aged 7-9 years of median height, the 90th percentile of SBP in the current study was lower and that of DBP was similar to the national reference values of Korea. For children aged < 7 years of median height, the reference value for SBP, but not that for DBP, was similar to that developed in the European study. CONCLUSION: Although further research is needed, our findings could be used to help identify high BP in children less than 10 years of age.

Extracellular Vesicles Derived from Senescent Fibroblasts Attenuate the Dermal Effect on Keratinocyte Differentiation.

The skin is a multilayered and primary defensive organ. Intimate intercellular communication in the skin is necessary to ensure effective surveillance. Extracellular vesicles (EVs) are being explored for their involvement in intercellular skin communication. The aim of this study was to evaluate how human dermal fibroblasts (HDFs) accelerate EV production during senescence and the effects of senescence-associated EVs on epidermal homeostasis. Replicative senescent HDFs were assessed with senescence-associated ß-galactosidase staining and the expression of senescence-related markers. Isolated EVs were characterized by dynamic light scattering and EV marker expression. EVs secreted from untreated young or senescent HDFs, or from those treated with a nSMase inhibitor, antioxidant, and lysosomal activity regulators, were determined by sandwich ELISA for CD81. Human epidermal keratinocytes were treated with young- and senescent HDF-derived EVs. Compared to young HDFs, senescent HDFs produced relatively high levels of EVs due to the increased nSMase activity, oxidative stress, and altered lysosomal activity. The nSMase inhibitor, antioxidant, and agents that recovered lysosomal activity reduced EV secretion in senescent HDFs. Relative to young HDF-derived EVs, senescent HDF-derived EVs were less supportive in keratinocyte differentiation and barrier function but increased proinflammatory cytokine IL-6 levels. Our study suggests that dermis-derived EVs may regulate epidermal homeostasis by reflecting cellular status, which provides insight as to how the dermis communicates with the epidermis and influences skin senescence.

A Novel Eye Drop Candidate for Age-Related Macular Degeneration Treatment: Studies on its Pharmacokinetics and Distribution in Rats and Rabbits.

Age-related macular degeneration (AMD) is wearing down of macula of retina, causing a blur or loss of vision in the center of the visual field. It can be categorized into dry or wet AMD. Until now, medical treatments for dry AMD have not been developed yet. The aim of this study was to evaluate pharmacokinetics (PKs) and tissue distribution of CK41016, a novel candidate for dry AMD, after intravenous (IV) or eye drop administration in rats and rabbits. In addition, a simple and sensitive bioanalytical method for CK41016 using ultra performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) was developed. PK parameters were estimated by compartmental analysis using a WinNonlin® software version 8.1 (a Certara™ company). A PK model of CK41016 was well-described by the two-compartment model. The tissue-to-plasma partition coefficient (Kp) of CK41016 was the highest in the vitreous humor of rats and the cornea of rabbits after eye drop administration. In addition, the Caco-2 cell transporter assay confirmed that CK41016 was not an active substrate for the efflux transporter. In summary, the PKs and tissue distribution of CK41016 were successfully evaluated and investigated whether this drug was a substrate of efflux transporters.

Monitoring Culicine Mosquitoes (Diptera: Culicidae) as a Vector of Flavivirus in Incheon Metropolitan City and Hwaseong-Si, Gyeonggi-Do, Korea, during 2019.

The flaviviruses are small single-stranded RNA viruses that are typically transmitted by mosquitoes or tick vectors and are etiological agents of acute zoonotic infections. The viruses are found around the world and account for significant cases of human diseases. We investigated population of culicine mosquitoes in central region of Korean Peninsula, Incheon Metropolitan City and Hwaseong-si. Aedes vexans nipponii was the most frequently collected mosquitoes (56.5%), followed by Ochlerotatus dorsalis (23.6%), Anopheles spp. (10.9%), and Culex pipiens complex (5.9%). In rural regions of Hwaseong, Aedes vexans nipponii was the highest population (62.9%), followed by Ochlerotatus dorsalis (23.9%) and Anopheles spp. (12.0%). In another rural region of Incheon (habitat of migratory birds), Culex pipiens complex was the highest population (31.4%), followed by Ochlerotatus dorsalis (30.5%), and Aedes vexans vexans (27.5%). Culex pipiens complex was the predominant species in the urban region (84.7%). Culicine mosquitoes were identified at the species level, pooled up to 30 mosquitoes each, and tested for flaviviral RNA using the SYBR Green-based RT-PCR and confirmed by cDNA sequencing. Three of the assayed 2,683 pools (989 pools without Anopheles spp.) were positive for Culex flaviviruses, an insect-specific virus, from Culex pipiens pallens collected at the habitats for migratory birds in Incheon. The maximum likelihood estimation (the estimated number) for Culex pipiens pallens positive for Culex flavivirus was 25. Although viruses responsible for mosquito-borne diseases were not identified, we encourage intensified monitoring and long-term surveillance of both vector and viruses in the interest of global public health.

Staphylococcus aureus-derived extracellular vesicles induce monocyte recruitment by activating human dermal microvascular endothelial cells in vitro.

BACKGROUND: Atopic dermatitis (AD) represents the most common inflammatory skin disorder in children showing massive infiltration of immune cells. The colonization of AD-afflicted skin by Staphylococcus aureus and S. aureus-derived extracellular vesicles (SEVs) has been associated with AD pathogenesis; however, the molecular mechanism underlying SEV-mediated inflammatory responses remains unclear. OBJECTIVE: We investigated how SEVs can mediate inflammatory responses in AD pathogenesis by examining the effect of SEVs on human dermal microvascular endothelia cells (HDMECs). METHODS: HDMECs were treated with SEVs, and the expression of cell adhesion molecules or cytokines was assessed using RT-qPCR, Western blot or cytokine array analyses. The receptor for SEVs and related signalling molecules in HDMECs were addressed and verified via gene knockdown or inhibitor experiments. The recruitment assay of human THP-1 monocytic cells on HDMECs was performed after SEV treatment in the presence or absence of the verified receptor or signalling molecule. RESULTS: SEVs, but not other gram-positive bacteria-derived extracellular vesicles, directly activated HDMECs by increasing the expression of cell adhesion molecules (E-selectin, VCAM1 and ICAM1) and that of IL-6, the inflammatory cytokine; consequently, they enhanced the recruitment of THP-1 monocytic cells to HDMECs. The SEV-induced HDMEC activation was dependent on Toll-like receptor 4 and the NF-κB signalling pathway, which was rapidly activated within 1 hour post-treatment and followed by an upregulation of cell adhesion molecules and IL-6 at later time-points. Moreover, SEV-mediated HDMEC responses were more rapid and intense than those induced by the same protein concentrations of S. aureus extracts. CONCLUSIONS & CLINICAL RELEVANCE: SEVs as proinflammatory factors could mediate immune cell infiltration in AD by efficiently inducing endothelial cell activation and monocyte recruitment, which may provide insights into alleviating the S. aureus-mediated onset or progression of AD and its phenotypes.

Exploring sex differences in human health risk assessment for PFNA and PFDA using a PBPK model.

Perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA), which are classified as perfluoroalkyl and polyfluoroalkyl substances (PFASs), have been widely used in industrial applications as a surface protectant. PFASs have been detected in wildlife and in humans around the globe. The purposes of this study are to develop and validate a physiologically based pharmacokinetic (PBPK) model for detecting PFNA and PFDA in male and female rats, and to apply the model to a human health risk assessment regarding the sex difference. A PBPK model of PFNA and PFDA was established based on an in vivo study in male and female rats. Analytes in biological samples (plasma, nine tissues, urine, and feces) were determined by ultra-liquid chromatography coupled tandem mass spectrometry (UPLC-MS/MS) method. PFNA and PFDA showed a gender differences in the elimination half-life and volume of distribution. The tissue-plasma partition coefficients were the highest in the liver in both male and female rats. The predicted rat plasma and urine concentrations simulated and fitted were in good agreement with the observed values. The PBPK models of PFNA and PFDA in male and female rats were then extrapolated to a human PBPK model based on human physiological parameters. The external doses were calculated at 3.35 ng/kg/day (male) and 17.0 ng/kg/day (female) for PFNA and 0.530 ng/kg/day (male) and 0.661 ng/kg/day (female) for PFDA. Human risk assessment was estimated using Korean biomonitoring values considering the gender differences. This study provides valuable insight into human health risk assessment regarding PFNA and PFDA exposure.

Reconstruction of Temporal Bone Defect Using a Vertically-Oriented Free Muscle-Sparing Rectus Abdominis Musculocutaneous Flap.

Reconstruction of a temporal bone defect after tumor ablation should provide watertight filling and adequate resurfacing. A muscle-sparing rectus abdominis musculocutaneous (ms-RAMC) flap with de-epithelized skin paddle has been used and early experience was reported. Case series enrolled 7 patients who underwent free ms-RAMC flap after tumor ablation for external auditory canal cancer. Vertically oriented flap was harvested with central strip of muscle. Distal skin paddle was de-epithelized to fill the bony defect. Immediate facial nerve reconstruction was performed whenever indicated. The average operation time for reconstruction was 280 minutes. No early complication was reported. An ms-RAMC flap with de-epithelized skin paddle can be used for temporal bone defect reconstruction with its anatomic consistency and technical simplicity. It can provide sufficient bulk for water tight packing that lasts after irradiation. The 11th intercostal nerve can be harvested during pedicle dissection. Muscle sparing technique could minimize donor-site morbidity.

Simultaneous Determination of Decursin, Decursinol Angelate, Nodakenin, and Decursinol of Angelica gigas Nakai in Human Plasma by UHPLC-MS/MS: Application to Pharmacokinetic Study.

Coumarins in Cham-dang-gwi, the dried root of Angelica gigas Nakai (AGN), possess pharmacological effects on anemia, pain, infection, and articular rheumatism. The AGN root containes decursin (D), decursinol angelate (DA), nodakenin, and decursinol (DOH), a major metabolite of D and DA. The aim of this study was to develop a simultaneous determination method for these four coumarins in human plasma using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Chromatographic separation was performed on dual columns (Kinetex® C18 column and Capcell core C18 column) with mobile phase consisting of water and acetonitrile at a flow rate of 0.3 mL/min using gradient elution. Multiple reaction monitoring was operated in positive ion mode with precursors to product ion transition values of m/z 328.9→228.8, 328.9→228.9, 409.4→248.8, and 246.8→212.9 to measure D, DA, nodakenin, and DOH, respectively. Linear calibration curves were fitted over concentration range of 0.05⁻50 ng/mL for these four components, with correlation coefficient greater than 0.995. Inter- and intra-day accuracies were between 90.60% and 108.24%. These precisions were within 11.19% for all components. The established method was then applied to a pharmacokinetic study for the four coumarins after usual dosing in Korean subjects.

Extracellular vesicles derived from Gram-negative bacteria, such as Escherichia coli, induce emphysema mainly via IL-17A-mediated neutrophilic inflammation.

Recent evidence indicates that Gram-negative bacteria-derived extracellular vesicles (EVs) in indoor dust can evoke neutrophilic pulmonary inflammation, which is a key pathology of chronic obstructive pulmonary disease (COPD). Escherichia coli is a ubiquitous bacterium present in indoor dust and secretes nanometer-sized vesicles into the extracellular milieu. In the current study, we evaluated the role of E. coli-derived EVs on the development of COPD, such as emphysema. E. coli EVs were prepared by sequential ultrafiltration and ultracentrifugation. COPD phenotypes and immune responses were evaluated in C57BL/6 wild-type (WT), IFN-γ-deficient, or IL-17A-deficient mice after airway exposure to E. coli EVs. The present study showed that indoor dust from a bed mattress harbors E. coli EVs. Airway exposure to E. coli EVs increased the production of proinflammatory cytokines, such as TNF-α and IL-6. In addition, the repeated inhalation of E. coli EVs for 4 wk induced neutrophilic inflammation and emphysema, which are associated with enhanced elastase activity. Emphysema and elastase activity enhanced by E. coli EVs were reversed by the absence of IFN-γ or IL-17A genes. In addition, during the early period, lung inflammation is dependent on IL-17A and TNF-α, but not on IFN-γ, and also on TLR4. Moreover, the production of IFN-γ is eliminated by the absence of IL-17A, whereas IL-17A production is not abolished by IFN-γ absence. Taken together, the present data suggest that E. coli-derived EVs induce IL-17A-dependent neutrophilic inflammation and thereby emphysema, possibly via upregulation of elastase activity.

Attenuation of collagen-induced arthritis by hyperbaric oxygen therapy through altering immune balance in favor of regulatory T cells.

Hyperbaric oxygen (HBO2) therapy is currently used for the treatment of chronic wounds, radiation-induced soft tissue necrosis, several oxygen-deficiency conditions and decompression sickness. In addition to the current indications, much empirical and experimental data suggest that HBO2 therapy may benefit autoimmune diseases by suppressing immunity, but the underlying mechanism is not well understood. Therefore, in the present study, we investigated whether HBO2 prevents the development of collagen-induced arthritis (CIA) in association with alteration of the immune balance between pro-inflammatory Th17 and anti-inflammatory regulatory T cells (Tregs). Arthritis was induced in DBA/1 mice by intradermal injection of type II collagen. Animals received either no treatment or 90 minutes of HBO2 (100% oxygen, at 2.0 ATA) daily beginning three days prior to the injection and were monitored for the development of arthritis. Six weeks later, joint tissues and spleens were analyzed for the alteration of immune balance between Th17 and Tregs by immunohistochemistry (IHC) or Western blot. Injection of collagen-induced extensive arthritis and extramedullary hematopoiesis in the spleens. Meanwhile, joint swelling and inflammatory tissue damages as well as extramedullary hematopoiesis were significantly less severe in the mice treated with HBO2. Both IHC and Western blot showed a decrease of FOXP3 and an increase of pSTAT3 expressions in the joints and spleens of the mice injected with collagen. This suggested that the systemic immune balance was biased toward Th17 cells, which was reversed by HBO2 therapy. These results suggested acute CIA associated with an immune balance favoring Th17 was attenuated by HBO2 in parallel with restoration of the immune balance to favor Tregs.