Prevalence and trends in obesity and severe obesity in Korean children and adolescents, 2007-2020: A population-based study.

BACKGROUND: The age-adjusted prevalence of child and adolescent obesity has been stabilized in the Korean population, although severe obesity has increased with adverse health effects. In this study, we detailed the prevalence of and trends in overweight, obesity, and severe obesity in Korean children and adolescents by age group and sex from a nationally representative sample, using a new, 2017 age- and sex-specific reference for body mass index. METHODS: We collected Korea National Health and Nutrition Examination Survey data from the years 2007-2020. A total of 23,595 subjects (11,210 females) aged 2-18 years were included in this study. We calculated the recent prevalence of overweight and obesity, including severe obesity, by weighted data from 2019 and 2020. RESULTS: The prevalence of overweight and obesity (class II and class III obesity) was 23.5% and 14.2% (2.5% and 0.5%), respectively. Males showed a higher prevalence of overweight and obesity. Adolescents aged 13-15 years showed the highest prevalence of severe obesity. A positive linear trend was significant for overweight (p = 0.025), class I obesity (p < 0.001), and class II obesity (p = 0.002) for both sexes and all ages combined. However, the trend of obesity prevalence was different in each subgroup. Comparing pre- and post- COVID-19 pandemic, obesity prevalence seemed to increase, but not significantly. CONCLUSIONS: Despite previous reports that obesity in children and adolescents has remained stable, we found that the prevalence of overweight, obesity, and severe obesity has increased in Korean children and adolescents. The effects of COVID-19 on this trend require further evaluation.

Molecular basis of weak A subgroups in the Korean population: Identification of three novel subgroup-causing variants in the ABO regulatory regions.

BACKGROUND: Recent studies on Chinese and Japanese populations have shown that weak ABO subgroups could be caused by variants in the major regulatory regions of ABO, the proximal promoter, +5.8-kb site, and CCAAT-binding factor/NF-Y binding site. We investigated the molecular basis of weak A subgroups in the Korean population. STUDY DESIGN AND METHODS: This study included 11 samples suspected to have a weak A subgroup. These samples were subjected to sequencing analysis of ABO exons 6 and 7. If no subgroup-causing variants were detected in this region, exons 1-5 and three major regulatory regions were sequenced. RESULTS: Sequencing analysis of exons 6 and 7 detected two known subgroup alleles (ABO*AW.10, n = 5; ABO*AEL.02, n = 2). The remaining four samples contained a sequence variant in the proximal promoter (g.4944C>T, n = 1; g.4954G>T, n = 1) or +5.8-kb site (g.10843T>C, n = 1; g.10935C>T, n = 1). Notably, three of the four variants (g.4944C>T, g.4954G>T, and g.10843T>C) have not been reported previously in weak ABO subgroups. CONCLUSION: This study provides the first evidence that alterations in the proximal promoter and + 5.8-kb site could account for a substantial proportion of weak A subgroups in the Korean population.

Upf1 regulates neurite outgrowth and branching by transcriptional and post-transcriptional modulation of Arc.

A large number of neuronal proteins must show correct spatiotemporal localization in order to carry out their critical functions. The mRNA transcript for the somatodendritic protein activity-regulated cytoskeleton-associated protein (Arc; also known as Arg3.1) contains two conserved introns in the 3' untranslated region (UTR), and was proposed to be a natural target for nonsense-mediated mRNA decay (NMD). However, a well-known NMD component Upf1 has differential roles in transcriptional and translational regulation of Arc gene expression. Specifically, Upf1 suppresses Arc transcription by enhancing destabilization of mRNAs encoding various transcription factors, including Mef2a. Upf1 also binds to the Arc 3'UTR, resulting in suppression of translation. Surprisingly, the Arc transcript escapes from Upf1-mediated NMD by binding to Ago2 (also known as miRISC), which blocks NMD and further suppresses Arc mRNA translation. Upf1 knockdown triggered sustained Arc expression, which contributes to Cofilin (also known as Cfl1) hyperphosphorylation and abnormal neuronal outgrowth and branching. Collectively, these data reveal that multiple levels of Upf1-mediated inhibition of Arc gene expression may allow neurons to more effectively respond to changes in neuronal activity.

Impact of the COVID-19 Pandemic on the Mental Health of Adolescent Students in Daegu, Korea.

BACKGROUND: In February 2020, as coronavirus disease 2019 (COVID-19) spread rapidly in Daegu, South Korea, students in that region experienced many emotional difficulties. In this study, we analyzed the stress and emotional crisis experienced by students during the COVID-19 pandemic, its causative factors, and the factors that affect negative emotions. METHODS: We identified the demographic information related to the experiences of unbearable stress and emotional crisis and their causal factors at three points in time: before the pandemic, during its peak, and at the time of the survey (2-3 months after the peak). In addition, we analyzed the factors related to depression and anxiety experienced by students during the COVID-19 pandemic. The Korean version of the Patient Health Questionnaire 9 and the Korean version of the Generalized Anxiety Disorder 7 was used to assess for depressive and anxiety symptoms in the subject students, respectively. RESULTS: A total of 8,177 students participated in the analysis, with 4,072 boys (49.8%), 4,105 girls (50.2%), and 4,463 middle school students (54.6%) and 3,177 high school students (45.4%). The percentage of students who experienced unbearable stress was 9% before the COVID-19 pandemic, increased to 16% at the peak of the COVID-19 pandemic, then decreased to 12.7% at the time of the survey. Stress was experienced more by girls (18.1% versus 13.8% in boys; χ² = 28.159, P < 0.001) and high school students (19.0% versus 13.5% in middle school students; χ² = 45.437, P < 0.001). Overall, 7.6% experienced emotional crises during the COVID-19 pandemic, which was more prevalent in girls (10.1% versus 5.2% in boys; χ² = 71.025, P < 0.001) and in high school students (8.8% versus 6.7% in middle school students; χ² = 12.996, P < 0.001). Depression and anxiety was seen in 19.8% and 12.3% of students during the COVID-19 pandemic, respectively. The risk factors for depression and anxiety included unbearable stress before the COVID-19 pandemic (P < 0.001), mental health (P = 0.044), and age (P = 0.040), whereas resilience was identified as a protective factor for depression and anxiety (P = 0.001). CONCLUSION: Students in Daegu experienced lots of mental difficulties since the COVID-19 pandemic. It will be necessary to improve stress management and resilience to improve students' mental health in disasters such as the COVID-19 pandemic.

Durable Oral Biofilm Resistance of 3D-Printed Dental Base Polymers Containing Zwitterionic Materials.

Poly(methyl methacralyate) (PMMA) has long been used in dentistry as a base polymer for dentures, and it is recently being used for the 3D printing of dental materials. Despite its many advantages, its susceptibility to microbial colonization remains to be overcome. In this study, the interface between 3D-printed PMMA specimens and oral salivary biofilm was studied following the addition of zwitterionic materials, 2-methacryloyloxyethyl phosphorylcholine (MPC) or sulfobetaine methacrylate (SB). A significant reduction in bacterial and biofilm adhesions was observed following the addition of MPC or SB, owing to their protein-repellent properties, and there were no significant differences between the two test materials. Although the mechanical properties of the tested materials were degraded, the statistical value of the reduction was minimal and all the properties fulfilled the requirements set by the International Standard, ISO 20795-2. Additionally, both the test materials maintained their resistance to biofilm when subjected to hydrothermal fatigue, with no further deterioration of the mechanical properties. Thus, novel 3D-printable PMMA incorporated with MPC or SB shows durable oral salivary biofilm resistance with maintenance of the physical and mechanical properties.

HNRNP A1 Promotes Lung Cancer Cell Proliferation by Modulating VRK1 Translation.

THeterogeneous nuclear ribonucleoprotein (HNRNP) A1 is the most abundant and ubiquitously expressed member of the HNRNP protein family. In recent years, it has become more evident that HNRNP A1 contributes to the development of neurodegenerative diseases. However, little is known about the underlying role of HNRNP A1 in cancer development. Here, we report that HNRNP A1 expression is significantly increased in lung cancer tissues and is negatively correlated with the overall survival of patients with lung cancer. Additionally, HNRNP A1 positively regulates vaccinia-related kinase 1 (VRK1) translation via binding directly to the 3' untranslated region (UTR) of VRK1 mRNA, thus increasing cyclin D1 (CCND1) expression by VRK1-mediated phosphorylation of the cAMP response element-binding protein (CREB). Furthermore, HNRNP A1 binding to the cis-acting region of the 3'UTR of VRK1 mRNA contributes to increased lung cancer cell proliferation. Thus, our study unveils a novel role of HNRNP A1 in lung carcinogenesis via post-transcriptional regulation of VRK1 expression and suggests its potential as a therapeutic target for patients with lung cancer.

RHD genotyping is recommended for all patients with serological weak-D phenotypes in Asian populations - Cases with coexistence of weak-D and Asia type DEL alleles results in complete expression of D-antigen.

Weak D types 1, 2, 3 and Asia type DEL (RHD 1227 G > A) can be treated as D-positive for purposes of Rho(D) immune globulin (RhIG) administration or selection of blood components for transfusion. To confirm these D variants, RHD genotyping can be used as a complementary to serologic tests. While ruling out weak D types 1,2,3 is useful in Caucasian populations, these are extremely rare in the Asian population, while Asia type DEL is relatively common. Distinguishing between true D-negative and Asia type DEL (RHD 1227 G > A) by genotyping has the same utility of distinguishing weak D types 1, 2, 3. The main difference between weak D and Asia type DEL is that the latter appears as D negative in conventional serologic methods, while the former will show positive in indirect anti-human immunoglobulin tests. RHD genotyping in apparent D-negative Asian patients has been established, yet the utility of genotyping in Asian patients with weakened D phenotypes require further investigation. We have observed cases of weak D patients with coexistence of a weak D allele and an Asia type DEL (RHD 1227 G > A) allele, we have found that antigen expression of D is as the weak D in indirect antiglobulin testing, yet all epitopes are detected with adsorption and elution assays. This is indicative of completeness of the D antigen epitope, and thus we suggest that all Asian patients with weakened D phenotypes can benefit from RHD genotyping.

Vaccinia-related kinase 2 plays a critical role in microglia-mediated synapse elimination during neurodevelopment.

During postnatal neurodevelopment, excessive synapses must be eliminated by microglia to complete the establishment of neural circuits in the brain. The lack of synaptic regulation by microglia has been implicated in neurodevelopmental disorders such as autism, schizophrenia, and intellectual disability. Here we suggest that vaccinia-related kinase 2 (VRK2), which is expressed in microglia, may stimulate synaptic elimination by microglia. In VRK2-deficient mice (VRK2KO ), reduced numbers of presynaptic puncta within microglia were observed. Moreover, the numbers of presynaptic puncta and synapses were abnormally increased in VRK2KO mice by the second postnatal week. These differences did not persist into adulthood. Even though an increase in the number of synapses was normalized, adult VRK2KO mice showed behavioral defects in social behaviors, contextual fear memory, and spatial memory.

Perioperative Fresh Red Blood Cell Transfusion May Negatively Affect Recipient Survival After Liver Transplantation.

OBJECTIVE: The aim of this study is to evaluate the association between fresh red blood cell (RBC) transfusion and recipient survival after liver transplantation. BACKGROUND: Fresh RBC products contain many viable leukocytes. Allogeneic leukocytes are responsible for adverse transfusion reactions in the immunocompromised host. METHODS: Among 343 liver transplant recipients who underwent perioperative RBC transfusion, 91 of 226 who did not receive fresh RBCs were matched with 91 of 117 who received fresh RBCs with 1:1 matching ratio using the propensity score based on the amount of transfused blood products and others. Survival analysis was performed using the Cox model. RESULTS: All transfused 3230 RBCs were leukoreduced and irradiated. Before matching, recipients in fresh RBC group received 3 U (2-6 U) of fresh RBCs. After a median follow-up of 60 months, 60 of 343 recipients (17.5%) died. Survival probability at 1/2/5 years after transplantation was 94.7%/92.0%/85.8% for nonfresh RBC group and 82.9%/76.0%/72.0% for fresh RBC group [death hazard ratio (HR) = 2.37 (1.43-3.94), P = 0.001]. In multivariable analysis, fresh RBC transfusion was significantly associated with increased death risk [HR = 2.33 (1.35-4.01), P = 0.002]. After matching, recipients in fresh RBC group received 3 U (2-5 U) of fresh RBCs. After a median follow-up of 56 months, 35 of 182 recipients (19.2%) died. Survival probability at 1/2/5 years was 95.6%/93.2%/86.0% for nonfresh RBC group and 85.7%/78.0%/73.0% for fresh RBC group [HR = 2.23 (1.43-3.94), P = 0.028]. Multivariable analysis confirmed a significance of fresh RBC transfusion [HR = 3.20 (1.51-6.78), P = 0.002]. CONCLUSION: Our findings suggest a potential negative impact of fresh RBC transfusion on the survival of patients undergoing liver transplantation.

Gait Variability Can Predict the Risk of Cognitive Decline in Cognitively Normal Older People.

BACKGROUND: The aim of this study was to investigate the association of gait speed and gait variability, an index of how much gait parameters, such as step time, fluctuate step-to-step, with risk of cognitive decline in cognitively normal elderly individuals. While high gait variability is emerging as an early indicator of dementing illnesses, there is little research on whether high gait variability predicts cognitive decline in cognitively normal elderly who have no evidence of cognitive impairment. METHODS: In this 4-year prospective cohort study on 91 community-dwelling cognitively normal elderly individuals without cerebral ischemic burden or Parkinsonism, we evaluated gait speed and step time variability using a tri-axial accelerometer placed on the center of body mass, and diagnosed mild cognitive impairment (MCI) according to the International Working Group on MCI. We performed Kaplan-Meier analysis with consecutive log-rank testing for MCI-free survival by cohort-specific tertiles of gait speed; hazard ratios (HR) of incident MCI were estimated using Cox proportional hazards regression analysis adjusted for age, sex, education level, Cumulative Illness Rating Scale score, GDS score, and presence of the apolipoprotein E ε4 allele. RESULTS: Out of the 91 participants in the baseline assessment, 87 completed one or more 2-year follow-up assessments, and the median duration of follow-up was 47.1 months. Kaplan-Meier curves of incident MCI show evident differences in risk by gait variability group (χ2 = 9.64, p = 0.002, log-rank test). Mean MCI-free survival in the high variability group was 12% shorter than in the mid-to-low tertile group (47.4 ± 1.74 [SD] vs. 54.04 ± 0.52 months), while it was comparable between gait speed groups (51.59 ± 0.70 vs. 50.64 ± 1.77 months; χ2 = 1.16, p = 0.281). In multivariate analysis, subjects with high gait variability showed about 12-fold higher risk of MCI (HR = 11.97, 95% CI = 1.29-111.37) than those with mid-to-low variability. However, those with slow gait speed showed comparable MCI risk to those with mid-to-high speed (HR = 5.04, 95% CI = 0.53-48.18). CONCLUSIONS: Gait variability may be a better predictor of cognitive decline than gait speed in cognitively normal elderly individuals without cerebral ischemic burden or Parkinsonism.

ABO Mistyping of cis-AB Blood Group by the Automated Microplate Technique.

BACKGROUND: The cis-AB phenotype, although rare, is the relatively most frequent of ABO subgroups in Koreans. To prevent ABO mistyping of cis-AB samples, our hospital has applied a combination of the manual tile method with automated devices. Herein, we report cases of ABO mistyping detected by the combination testing system. METHODS: Cases that showed discrepant results by automated devices and the manual tile method were evaluated. These samples were also tested by the standard tube method. The automated devices used in this study were a QWALYS-3 and Galileo NEO. Exons 6 and 7 of the ABO gene were sequenced. RESULTS: 13 cases that had the cis-AB allele showed results suggestive of the cis-AB subgroup by manual methods, but were interpreted as AB by either automated device. This happened in 87.5% of these cases by QWALYS-3 and 70.0% by Galileo NEO. Genotyping results showed that 12 cases were ABO*cis-AB01/ABO*O01 or ABO*cis-AB01/ABO*O02, and one case was ABO*cis-AB01/ ABO*A102. CONCLUSION: Cis-AB samples were mistyped as AB by the automated microplate technique in some cases. We suggest that the manual tile method can be a simple supplemental test for the detection of the cis-AB phenotype, especially in countries with relatively high cis-AB prevalence.

Application of a portable microscopic cell counter for the counting of residual leukocytes in leukoreduced apheresis platelet concentrates in a hospital blood bank.

While a portable microscopic cell counter has been evaluated to enumerate residual white blood cells (WBCs) in red blood cells and platelet concentrates at blood centers, it has not yet been assessed in a hospital blood bank. We investigated the performance of this device and evaluated its accuracy, along with its benefits in time management. Residual WBCs from each of 100 apheresis platelet specimens were measured manually using a Nageotte chamber, along with flow cytometry methods and an ADAM-rWBC automated instrument (NanoEnTek, Seoul, South Korea). The efficiency was calculated by measuring the time required for the analysis of one specimen ten times consecutively. Flow cytometry and the ADAM-rWBC were able to detect four sporadic cases that had residual WBCs exceeding 1/µL that were not detected by the manual method. Analysis time was the shortest with the ADAM-rWBC, followed by flow cytometry and the manual method. Our data suggest that hospital blood banks require quality control of residual WBCs; among the methods evaluated in this study, the portable microscopic cell counter offers the best time efficiency.

Contributions of CAG repeat length in the androgen receptor gene and androgen profiles to premature pubarche in Korean girls.

The CAG repeat length of the androgen receptor (AR) gene, which exhibits an inverse relationship to AR sensitivity, might influence the development of the pubarche along with hyperandrogenemia. There are ethnic differences in the AR CAG repeat length, however, no Asian studies on premature pubarche (PP) have been reported, including Korea. Our objectives were to examine the hormone levels and AR CAG repeat length, and to assess their contributions to PP in Korean girls. Subjects with PP (n=16) and normal pubarche (NP, n=16), and normal controls (NC, n=16) were enrolled. The levels of dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEAS), 17-hydroxyprogesterone (17-OHP), and free testosterone (FT) were checked. The methylation-weighted (MW) average CAG repeat lengths were analyzed. The median ages at pubarche were 7.4 and 8.9 years in the PP and NP groups, respectively, and the levels of 17-OHP, DHEAS, and FT were similar in both groups. The PP group exhibited a higher DHEAS:DHEA ratio than the NP group (P=0.014). The medians of the MW average CAG repeat length of the AR gene were 22.4 for all subjects and did not differ among the PP (22.3), NP (22.4), and NC (22.2) groups. The AR CAG repeat lengths in the PP and NP groups did not correlate with DHEAS or FT levels. These results suggest that the AR CAG repeat length was not involved in the development of PP in Korean girls. However, excessive adrenal androgen levels, particularly those caused by increased sulfotransferase activity, might be important in the pathogenesis of PP.

Orthodontic Treatment in Conjunction with Twin-bock Treatment and Growth Hormone Therapy in Silver Russell Syndrome.

Silver-Russell syndrome (SRS) is a very rare genetic disorder characterized by intrauterine growth retardation, short stature, and typical craniofacial abnormalities including micrognathia. While growth hormone (GH) therapy in children with SRS significantly improves somatic growth, functional orthopedic treatment can also be effective in adolescents with mandibular deficiency. We report the effects of Phase 1 functional orthopedic treatment of a twin-block appliance in conjunction with GH administration in a 9-year-old boy with GH deficiency and SRS, and the result of the subsequent Phase 2 orthodontic treatment.

Prevalence and trends of dementia in Korea: a systematic review and meta-analysis.

Through a systematic review and meta-analysis of epidemiological studies on dementia, we assessed the prevalence of dementia and its subtypes-Alzheimer' disease (AD) and vascular dementia (VaD)-in Korea. We searched for epidemiological studies on dementia published in 1990-2013 using PubMed, Scopus, EMBASE, KoreaMed, KISS, and RiCH. Dementia prevalence in elderly patients (aged≥65 yr) was 9.2% (95% confidence interval [CI], 8.2%-10.4%) from 11 studies, which was higher than those from Western and other Asian countries. AD was the most prevalent dementia type, with a prevalence of 5.7% (95% CI, 5.0%-6.4%) from 10 studies compared with 2.1% (95% CI, 1.6%-2.7%) for VaD from 9 studies. The age-specific prevalence of dementia approximately doubled with each 5.8-yr increase of age. Although a significant increasing trend of dementia prevalence was not observed, it increased slightly from 7.3% to 8.7% after 2005; AD prevalence increased after 1995 and VaD prevalence decreased after the early 2000s. The AD/VaD ratio increased from 1.96 in the early 1990s to 4.13 in the 2010s, similar to the worldwide ratio. Owing to this high prevalence in the aging population, dementia will impose significant economic burdens to Korean society.

Low concentration zinc oxide nanoparticles enrichment enhances bacterial and pro-inflammatory resistance of calcium silicate-based cements.

Calcium silicate-based cement (CSC) is a commonly used material in endodontic treatment. However, it has limited antibacterial activity, especially for cases involving primary infections. Zinc oxide nanoparticles (ZnO-NPs) are recognized for their potential in biomedical applications due to their antibacterial properties and ability to reduce inflammation. This study aims to optimize CSC by incorporating ZnO-NPs to maintain its physical properties, enhance its antibacterial activity, and reduce the production of pro-inflammatory cytokines. ZnO-NPs were integrated into a commercial CSC (Endocem MTA) at 1 wt% (CSZ1) or 3 wt% (CSZ3). Setting time, compressive strength, and X-ray diffraction were then measured. In addition, pH, calcium ion release, and zinc ion release were measured for 7 days. Antibacterial activity against Enterococcus faecalis and viability of murine macrophages (RAW264.7) were determined using colorimetric assays. Gene expression levels of pro-inflammatory cytokines in lipopolysaccharide induced RAW264.7 were evaluated using quantitative polymerase chain reaction. Results were compared to an unmodified CSC group. In the CSZ3 group, there was a significant increase of approximately 12% in setting time and a reduction of about 36.4% in compressive strength compared to the control and CSZ1 groups. The presence of ZnO-NPs was detected in both CSZ1 and CSZ3. Both CSC and CSZ1 groups maintained an alkaline pH and released calcium ions, while zinc ions were significantly released in the CSZ1 group. Additionally, CSZ1 showed a 1.8-fold reduction of bacterial activity and exhibited around 85% reduction in colony-forming units compared to the CSC group. Furthermore, the CSZ1 group showed a more than 39% reduction in pro-inflammatory cytokine levels compared to the CSC group. Thus, enriching CSC with 1 wt% ZnO-NPs can enhance its antibacterial activity and reduce pro-inflammatory cytokines without showing any tangible adverse effects on its physical properties.

Development, validation, and usability evaluation of machine learning algorithms for predicting personalized red blood cell demand among thoracic surgery patients.

INTRODUCTION: Preparing appropriate red blood cells (RBCs) before surgery is crucial for improving both the efficacy of perioperative workflow and patient safety. In particular, thoracic surgery (TS) is a procedure that requires massive transfusion with high variability for each patient. Hence, the precise prediction of RBC requirements for individual patients is becoming increasingly important. This study aimed to 1) develop and validate a machine learning algorithm for personalized RBC predictions for TS patients and 2) assess the usability of a clinical decision support system (CDSS) integrating this artificial intelligence model. METHODS: Adult patients who underwent TS between January 2016 and October 2021 were included in this study. Multiple models were developed by employing both traditional statistical- and machine-learning approaches. The primary outcome evaluated the model's performance in predicting RBC requirements through root mean square error and adjusted R2. Surgeons and informaticians determined the precision MSBOS-Thoracic Surgery (pMSBOS-TS) algorithm through a consensus process. The usability of the pMSBOS-TS was assessed using the System Usability Scale (SUS) survey with 60 clinicians. RESULTS: We identified 7,843 cases (6,200 for training and 1,643 for test sets) of TSs. Among the models with variable performance indices, the extreme gradient boosting model was selected as the pMSBOS-TS algorithm. The pMSBOS-TS model showed statistically significant lower root mean square error (mean: 3.203 and 95% confidence interval [CI]: 3.186-3.220) compared to the calculated Maximum Surgical Blood Ordering Schedule (MSBOS) and a higher adjusted R2 (mean: 0.399 and 95% CI: 0.395-0.403) compared to the calculated MSBOS, while requiring approximately 200 fewer packs for RBC preparation compared to the calculated MSBOS. The SUS score of the pMSBOS-TS CDSS was 72.5 points, indicating good acceptability. CONCLUSIONS: We successfully developed the pMSBOS-TS capable of predicting personalized RBC transfusion requirements for perioperative patients undergoing TS.

Pharmacokinetic and Pharmacodynamic Modeling Analysis of Delpazolid (LCB01-0371) in Adult Patients with Pulmonary Tuberculosis.

Delpazolid (LCB01-0371) is a novel oxazolidinone derivative with a good safety profile for treating gram-positive pathogenic infections such as Mycobacterium abscessus, a highly pathogenic drug-resistant Mycobacterium. In this study, we evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of delpazolid after 14 days of multiple oral administration, using data from adult patients with pulmonary tuberculosis. 800 mg once a day, 400 mg twice a day, 800 mg twice a day, and 1200 mg once a day delpazolid for 14 days were tested in 63 patients with pulmonary tuberculosis. For PK blood collection, inpatient and outpatient scheduling were separately implemented. Plasma concentrations of delpazolid were measured at visits 2, 4, 6, and 8 in outpatients, and four sparse blood samples were measured in inpatients. PD models were sequentially fitted using individual PK parameter estimates obtained from PK compartmental models. For PK modeling, 180 plasma concentrations of delpazolid from 56 patients were included. A two-compartment mixed first- and zero-order absorption model best described the time course of plasma concentration. For the PD model, 448 bacterial titer data from 60 patients were used. The time course of bacterial titers (log10 CFU/mL) was described by a model that consists of the growth and killing rate of bacteria with the sigmoid Emax model. The PK-PD simulation suggested that the bacterial titers are the lowest on the 800 mg bid regimen among the four, consistent with observed data, as all regimens substantially decrease. In the dose-response relationship, the effectiveness of delpazolid was suggested.

Enhancing biofilm resistance and preserving optical translucency of 3D printed clear aligners through carboxybetaine-copolymer surface treatment.

OBJECTIVES: This study aimed to use a carboxybetaine methacrylate (CBMA) copolymer solution to surface treat 3D printed clear aligners at different fabrication stages, to impart antifouling properties, and assess the surface treatment at various fabrication stages' impact on physico-mechanical characteristics. METHODS: Surface treatments using a blend of 2-hydroxyethyl methacrylate (HEMA) and CBMA, termed CCS, were performed at various stages of 3D printed clear aligner fabrication. Experimental groups, CB1, CB2, and CB3, were determined by the stage of surface treatment during post-processing. CB1, CB2, and CB3 received treatment before post-curing, after post-curing, and after post-processing, respectively. Untreated samples served as controls. Physical and mechanical properties were assessed through tensile testing, Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and UV-Vis spectroscopy. The surface was further characterized through scanning electron microscopy and contact angle measurements. The cytotoxicity was assessed with 7-day elution and agar diffusion assays. Lastly, bacterial biofilm resistance was evaluated using confocal laser scanning microscopy. Crystal violet assay was performed using Streptococcus mutans. RESULTS: Surface treatment during CB1 stage exerted the most significantly unfavorable influence on properties of the 3D printed aligner resin. CB2 samples showed the maximum preservation of translucency even after 7-day aging. CB2 and CB3 phases showed enhanced hydrophilicity of sample surfaces with reduced adhesion of multispecies biofilm and S. mutans. SIGNIFICANCE: Application of CCS surface treatment immediately after post-curing (CB2) can enhance the biofilm resistance of 3D printed clear aligners while maintaining high fidelity to optical translucency and constituent mechanical properties.