Assisted reproductive techniques and subsequent risk of asthma and allergic rhinitis in offspring: a nationwide birth cohort study in South Korea.

OBJECTIVE: The relationship between assisted reproductive techniques (ART) and the risk of asthma and allergic rhinitis (AR) is controversial. Thus, we aimed to investigate the relationship between ART and the risk of asthma and AR in a nationwide, large-scale birth cohort. PATIENTS AND METHODS: This study utilized the National Health Insurance Service data in South Korea to conduct a nationwide, large-scale, population-based birth cohort. We included all infants born between 2017 and 2018. AR, asthma, food allergies, and atopic dermatitis were defined using the International Classification of Diseases tenth edition codes. Asthma was classified as allergic or non-allergic based on accompanying allergic diseases (AR, food allergy, or atopic dermatitis). Using 1:10 propensity score matching, we compared infants conceived through ART with those conceived naturally (non-ART). After matching, logistic regression was used to compare the hazard ratio for asthma and AR between the two groups. RESULTS: We included 543,178 infants [male infants, 280,194 (51.38%)]. After matching, 8,925 and 74,229 infants were selected for the ART and non-ART groups, respectively. The ART group showed a decreased risk of asthma in the offspring [adjusted hazard ratio (aHR), 0.45; 95% confidence interval (CI), 0.41-0.48]. Similarly, for AR, being conceived by ART was associated with a decreased risk of AR (aHR, 0.25; 95% CI, 0.12-0.37). ART offspring showed a decreased risk of asthma and AR in offspring compared to that observed in non-ART offspring. CONCLUSIONS: Our study offers important insights for clinicians, researchers, and parents regarding the health outcomes of ART-conceived infants and enhances our understanding of ART's impact on respiratory health.

Saturation of Fishbone Instability by Self-Generated Zonal Flows in Tokamak Plasmas.

Gyrokinetic simulations of the fishbone instability in DIII-D tokamak plasmas find that self-generated zonal flows can dominate the nonlinear saturation by preventing coherent structures from persisting or drifting in the energetic particle phase space when the mode frequency down-chirps. Results from the simulation with zonal flows agree quantitatively, for the first time, with experimental measurements of the fishbone saturation amplitude and energetic particle transport. Moreover, the fishbone-induced zonal flows are likely responsible for the formation of an internal transport barrier that was observed after fishbone bursts in this DIII-D experiment. Finally, gyrokinetic simulations of a related ITER baseline scenario show that the fishbone induces insignificant energetic particle redistribution and may enable high performance scenarios in ITER burning plasma experiments.

The impact of discontinuing single-room isolation of patients with vancomycin-resistant enterococci: a quasi-experimental single-centre study in South Korea.

OBJECTIVES: There is limited data on the effects of discontinuing single-room isolation while maintaining contact precautions, such as the use of gowns and gloves. In April 2021, our hospital ceased single-room isolation for patients with vancomycin-resistant enterococci (VRE) because of single-room unavailability. This study assessed the impact of this policy by examining the incidence of hospital-acquired VRE bloodstream infections (HA-VRE BSI). METHODS: This retrospective quasi-experimental study was conducted at a tertiary-care hospital in Seoul, South Korea. Time-series analysis was used to evaluate HA-VRE BSI incidence at the hospital level and in the haematology unit before (phase 1) and after (phase 2) the policy change. RESULTS: At the hospital level, HA-VRE BSI incidence level (VRE BSI per 1000 patient-days per month) and trend did not change significantly between phase 1 and phase 2 (coefficient -0.015, 95% confidence interval (CI): -0.053 to 0.023, P=0.45 and 0.000, 95% CI: -0.002 to 0.002, P=0.84, respectively). Similarly, HA-VRE BSI incidence level and trend in the haematology unit (-0.285, 95% CI: -0.618 to 0.048, P=0.09 and -0.018, 95% CI: -0.036 to 0.000, P = 0.054, respectively) did not change significantly across the two phases. CONCLUSIONS: Discontinuing single-room isolation of VRE-colonized or infected patients was not associated with an increase in the incidence of VRE BSI at the hospital level or among high-risk patients in the haematology unit. Horizontal intervention for multi-drug-resistant organisms, including measures such as enhanced hand hygiene and environmental cleaning, may be more effective at preventing VRE transmission.

Management of newborns and healthcare workers exposed to isoniazid-resistant congenital tuberculosis in the neonatal intensive care unit.

BACKGROUND: Management of newborns and healthcare workers (HCWs) exposed to congenital tuberculosis (TB) in the neonatal intensive care unit (NICU) has been reported rarely. AIM: To outline a contact investigation process for individuals exposed to congenital TB in the NICU and investigate nosocomial transmission. Additionally, to assess the efficacy and safety of window prophylaxis in exposed newborns. METHODS: A baby, born at a gestational age of 28 + 1 weeks, was diagnosed with isoniazid-resistant congenital TB on the 39th day of admission to the level IV NICU. Newborns and HCWs exposed cumulatively for ≥8 h underwent contact investigation and follow-up for a year. FINDINGS: Eighty-two newborns underwent contact investigation. All newborns displayed normal chest X-rays, and 42 hospitalized newborns tested negative for acid-fast bacilli stain and Xpert® MTB/RIF assay in their endotracheal sputum or gastric juices. Eighty received window prophylaxis: six of 75 on rifampin experienced mild adverse events, and none of the five on levofloxacin. After 12 weeks, five (6.1%) had a positive tuberculin skin test, all of whom had already received the Bacillus Calmette-Guérin vaccine and tested negative on TB interferon-gamma releasing assay. Of 119 exposed HCWs, three (2.5%) were diagnosed with latent TB infection and completed a four-month rifampin therapy. There was no active TB disease among exposed newborns and HCWs during a one-year follow-up. CONCLUSION: Timely diagnosis of congenital TB is crucial for minimizing transmission among exposed neonates and HCWs in the NICU setting. In cases of isoniazid-resistant index patients, even premature newborns may consider the use of rifampin or levofloxacin for window prophylaxis.

Ameliorating effect of 2'-Fucosyllactose and 6'-Sialyllactose on lipopolysaccharide-induced intestinal inflammation.

Human milk oligosaccharides (HMO) affect gut microbiota during neonatal development, particularly with respect to the immune system. Bovine milk-based infant formulas have low oligosaccharide contents. Thus, efforts to fortify infant formulas with HMO are being undertaken. Two major HMO, 2'-fucosyllactose (2'-FL) and 6'-sialyllactose (6'-SL), exert anti-inflammatory effects; however, the associations between anti-inflammatory effects induced by 2'-FL and 6'-SL co-treatment and gut microbiota composition and metabolite modulation remain unclear. Therefore, in this study, we evaluated the effects of a mixture of these HMO. To determine the optimal HMO ratio for anti-inflammatory effects and elucidate its mode of action, LPS-induced inflammatory HT-29 epithelial cells and intestinal inflamed suckling mice were treated with various mixtures of 2'-FL and 6'-SL. 2'-FL:6'-SL ratio of 5:1 was identified as the most effective pre-treatment HMO mixture in vitro; thus, this ratio was selected and used for low, middle, and high-dose treatments for subsequent in vivo studies. In vivo, high-dose HMO treatment restored LPS-induced inflammation symptoms, such as body weight loss, colon length reduction, histological structural damage, and intestinal gene expression related to inflammatory responses. High-dose HMO was the only treatment that modulated the major phyla Bacteroidetes and Firmicutes and the genera Ihubacter, Mageeibacillus, and Saccharofermentans. These changes in microbial composition were correlated with intestinal inflammation-related gene expression and short-chain fatty acid production. To our knowledge, our study is the first to report the effects of Ihubacter, Mageeibacillus, and Saccharofermentans on short chain fatty acid levels, which can subsequently affect inflammatory cytokine and tight junction protein levels. Conclusively, the HMO mixture exerted anti-inflammatory effects through changes in microbiota and metabolite production. These findings suggested that supplementation of infant formula with HMO may benefit formula-fed infants by forming unique microbiota contributing to neonatal development.

Multi-peak Light-emitting Diode Curing Units and Polymerization of 3D-printed Crown and Bridge Resin.

PURPOSE: This study aimed to evaluate the substitutive and additive efficacy of multi-peak light-emitting diode (LED) curing units for post-curing of a three-dimensional- (3D-) printed crown and bridge resin. METHODS: A total of 792 disc- and 180 bar-shaped specimens were printed with a crown and bridge resin (NextDent C&B MFH) and post-cured using two LED curing units (VALO Cordless and Bluephase N G4) in fast and standard modes. Conventional post-curing (LC-3D Print Box, Group PC) was compared with LED-only curing (Groups V1, V2, B1, and B2) and LED-combined curing (Groups PV1, PV2, PB1, and PB2) in terms of microhardness, flexural strength, degree of conversion (DC), and CIE L*a*b* color and translucency parameters. Cytotoxicity of the resin eluates was evaluated using the WST-1 assay. Temperature increases on the resin surface were measured with infrared thermography. Data were statistically analyzed using ANOVA and Kruskal-Wallis tests (α=0.05). RESULTS: The microhardness and flexural strength in Groups V1, V2, B1, and DC in all LED-only groups were lower than in other groups (p<0.05). Larger color disparities existed between Group PC and all LED-only groups than between Group PC and the others (p<0.05). There was no significant difference in cytotoxicity among the groups. The temperature increase was lowest in Groups V1 and PV1 during light curing (p<0.05). CONCLUSIONS: Post-curing by multi-peak LED curing units was not as effective as the conventional post-curing device. Additional post-curing by LED curing units did not improve the material properties.

Search for Boosted Dark Matter in COSINE-100.

We search for energetic electron recoil signals induced by boosted dark matter (BDM) from the galactic center using the COSINE-100 array of NaI(Tl) crystal detectors at the Yangyang Underground Laboratory. The signal would be an excess of events with energies above 4 MeV over the well-understood background. Because no excess of events are observed in a 97.7 kg·yr exposure, we set limits on BDM interactions under a variety of hypotheses. Notably, we explored the dark photon parameter space, leading to competitive limits compared to direct dark photon search experiments, particularly for dark photon masses below 4 MeV and considering the invisible decay mode. Furthermore, by comparing our results with a previous BDM search conducted by the Super-Kamionkande experiment, we found that the COSINE-100 detector has advantages in searching for low-mass dark matter. This analysis demonstrates the potential of the COSINE-100 detector to search for MeV electron recoil signals produced by the dark sector particle interactions.

A RARE CASE OF GRAVES' THYROTOXICOSIS WITH CONCOMITANT PULMONARY ALVEOLAR PROTEINOSIS.

Background: Graves' disease results in various clinical cardio-pulmonary manifestations such as tachycardia, atrial fibrillation, and pulmonary edema. Clinical Case: A 62-year-old woman presented with palpitations and dyspnea. Laboratory and radiologic examination revealed markedly elevated free T4 (4.79 ng/dL), T3 (4.42 ng/mL), lowered TSH (0.01 uIU/mL), atrial fibrillation and multifocal lung haziness. She was initially diagnosed with atrial fibrillation with pulmonary edema, which subsequently changed to pulmonary alveolar proteinosis by further evaluations such as computed tomography and bronchoscopic biopsy. Conclusion: Pulmonary alveolar proteinosis is a rare lung disease. Clinicians should carefully assess lung lesions in thyrotoxicosis patients as they can be easily mistaken for pulmonary edema in clinical practice.

Synaptic Activity Causes Minute-scale Changes in BAF Complex Composition and Function.

Genes encoding subunits of the SWI/SNF or BAF ATP-dependent chromatin remodeling complex are among the most enriched for deleterious de novo mutations in intellectual disabilities and autism spectrum disorder, but the causative molecular pathways are not fully known 1,2 . Synaptic activity in neurons is critical for learning and memory and proper neural development 3 . Neural activity prompts calcium influx and transcription within minutes, facilitated in the nucleus by various transcription factors (TFs) and chromatin modifiers 4 . While BAF is required for activity-dependent developmental processes such as dendritic outgrowth 5-7 , the immediate molecular consequences of neural activity on BAF complexes and their functions are unknown. Here we mapped minute-scale biochemical consequences of neural activity, modeled by membrane depolarization of embryonic mouse primary cortical neurons, on BAF complexes. We used acute chemical perturbations of BAF ATPase activity and kinase signaling to define the activity-dependent effects on BAF complexes and activity-dependent BAF functions. Our studies found that BAF complexes change in subunit composition and are selectively phosphorylated within 10 minutes of depolarization. Increased levels of the core PBAF subunit Baf200/ Arid2 , uniquely containing an RFX-like DNA-binding domain, are concurrent with ATPase-dependent opening of chromatin at RFX/X-box motifs. Changes in BAF composition and phosphorylation lead to the regulation of chromatin accessibility for critical neurogenesis TFs. These biochemical effects are a convergent phenomenon downstream of multiple growth factor signaling pathways in mouse neurons and fibroblasts suggesting that BAF integrates signaling information from the membrane. In support of such a membrane-to-nucleus signaling cascade, we also identified a BAF-interacting kinase, Dclk2, whose inhibition attenuates BAF phosphorylation selectively. Our findings support a direct role of BAF complexes in responding to synaptic activity to regulate TF binding and transcription.

Impact of carbapenem-targeted antimicrobial stewardship interventions: an interrupted time-series analysis.

BACKGROUND: The development of carbapenem-resistant Gram-negative bacilli (CR-GNB) is largely favoured by indiscriminate and prolonged carbapenem use, which is a significant contributing factor. AIM: To evaluate the impact of two carbapenem antibiotic stewardship programme interventions on both carbapenem prescriptions and the clinical isolation rates of CR-GNBs, using interrupted time-series analysis. METHODS: A time-series analysis was performed using data for carbapenem usage from a tertiary hospital in South Korea from January 2017 to July 2022. Two carbapenem antibiotic stewardship programme interventions were implemented sequentially: (i) a prospective audit and feedback (PAF) from November 2018 to April 2020 (intervention 1), and (ii) preauthorization from May 2020 to August 2020 (intervention 2). Monthly carbapenem usage and incidence of CR-GNB before and after each intervention were compared using an autoregressive integrated moving average model. FINDINGS: Implementation of PAF resulted in a significant reduction in carbapenem consumption, followed by an additional decrease after the preauthorization was implemented. The incidence of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae increased after intervention 1, but there was a significant change from an increasing trend to a stationary trend after intervention 2. The incidence of carbapenem-resistant Pseudomonas aeruginosa, which had increased during the baseline period, became stationary after intervention 1. A significant decrease was observed in the incidence of carbapenem-resistant Acinetobacter baumannii during the implementation of intervention 1 and 2. CONCLUSION: This study emphasizes the importance of adopting comprehensive antibiotic management and rigorous infection control to prevent infections caused by antibiotic-resistant bacteria.

Appropriateness of antibiotic use for patients with asymptomatic bacteriuria or urinary tract infection with positive urine culture: a retrospective observational multi-centre study in Korea.

BACKGROUND: Antibiotic resistance threatens public health worldwide, and inappropriate use of antibiotics is one of the main causes. AIM: To evaluate qualitative use of antibiotics in asymptomatic bacteriuria (ABU) and urinary tract infection (UTI). METHODS: Cases of positive urine culture (≥105 colony-forning units/mL) performed in inpatient, outpatient and emergency departments in April 2021 were screened in 26 hospitals in the Republic of Korea. The cases were classified as ABU, lower UTI and upper UTI. The appropriateness of antibiotic use was evaluated retrospectively by infectious disease specialists using quality indicators based on clinical guidelines for ABU and UTI. RESULTS: This study included a total of 2697 patients with ABU or UTI. The appropriateness of antibiotic use was assessed in 1157 patients with ABU, and in 677 and 863 patients with lower and upper UTI, respectively. Among the 1157 patients with ABU, 251 (22%) were prescribed antibiotics without appropriate indications. In 66 patients with ABU in which antibiotics were prescribed with appropriate indications, the duration was adequate in only 23 (34.8%) patients. The appropriateness of empirical and definite antibiotics was noted in 527 (77.8%) and 353 (68.0%) patients with lower UTI, and 745 (86.3%) and 583 (78.2%) patients with upper UTI, respectively. The duration of antibiotics was adequate in 321 (61.8%) patients with lower UTI and 576 (78.7%) patients with upper UTI. CONCLUSIONS: This nationwide qualitative assessment of antibiotic use in ABU and UTI revealed that antibiotics were often prescribed inappropriately, and the duration of antibiotics was unnecessarily prolonged.

First Observation of the ß3αp Decay of

The ß-delayed proton decay of ^{13}O has previously been studied, but the direct observation of ß-delayed 3αp decay has not been reported. Rare 3αp events from the decay of excited states in ^{13}N^{⋆} provide a sensitive probe of cluster configurations in ^{13}N. To measure the low-energy products following ß-delayed 3αp decay, the Texas Active Target (TexAT) time projection chamber was employed using the one-at-a-time ß-delayed charged-particle spectroscopy technique at the Cyclotron Institute, Texas A&M University. A total of 1.9×10^{5} ^{13}O implantations were made inside the TexAT time projection chamber. A total of 149 3αp events were observed, yielding a ß-delayed 3αp branching ratio of 0.078(6)%. Four previously unknown α-decaying excited states were observed in ^{13}N at 11.3, 12.4, 13.1, and 13.7 MeV decaying via the 3α+p channel.

Fabrication of THz corrugated wakefield structure and its high power test.

We present overall process for developing terahertz (THz) corrugated structure and its beam-based measurement results. 0.2-THz corrugated structures were fabricated by die stamping method as the first step demonstration towards GW THz radiation source and GV/m THz wakefield accelerator. 150-[Formula: see text]m thick disks were produced from an OFHC (C10100) foil by stamping. Two types of disks were stacked alternately to form 46 mm structure with [Formula: see text] 170 corrugations. Custom assembly was designed to provide diffusion bonding with a high precision alignment of disks. The compliance of the fabricated structure have been verified through beam-based wakefield measurement at Argonne Wakefield Accelerator Facility. Both measured longitudinal and transverse wakefield showed good agreement with simulated wakefields. Measured peak gradients, 9.4 MV/m/nC for a long single bunch and 35.4 MV/m/nC for a four bunch trains, showed good agreement with the simulation.

Association between obsessive-compulsive disorder and the risk of schizophrenia using the Korean National Health Insurance Service-National Sample Cohort: a retrospective cohort study.

AIMS: Obsessive-compulsive disorder (OCD) and schizophrenia are often reported as co-morbid conditions. However, the evidence of an association between OCD and the risk of schizophrenia is limited. This study investigated the risk of schizophrenia in patients newly diagnosed with OCD using a nationally representative sample cohort in South Korea. METHODS: Data were obtained from the 2002-2013 Korean National Health Insurance Service-National Sample Cohort of the National Health Insurance Service. Using propensity score matching, 2509 patients with OCD and a control group of 7527 patients were included in the analysis. Chi-squared tests were used to investigate and compare the general characteristics of the study population. The risk of schizophrenia was analysed using the Cox proportional hazard model. RESULTS: The incidence rate was 45.79/10 000 person-year for patients with OCD and 4.19/10 000 person-year for patients without OCD. Patients with OCD had a higher risk of schizophrenia compared to the control group after adjusting for covariates (hazard ratio = 10.46, 95% confidence interval = 6.07-18.00). CONCLUSIONS: This study identified an association between the diagnosis of OCD and the risk of schizophrenia in a South Korean national representative cohort. Further research using a prospective design to clarify the causality of OCD in schizophrenia in a controlled environment should be conducted to validate these findings.

Evaluation of the efficacy and safety of NVP-1203 and aceclofenac in patients with acute low back pain and muscle spasm: A randomized, double-blind, active-controlled, parallel, multicenter, phase 3 clinical trial.

OBJECTIVE: Acute low back pain (LBP) is a common condition that can be chronic if not properly treated. Aceclofenac and eperisone hydrochloride are commonly prescribed drugs for acute LBP and muscle spasms. Therefore, NVP-1203, a fixed-dose combination of 100 mg aceclofenac and 75 mg eperisone hydrochloride, is being developed. This study aimed to evaluate the efficacy and safety of NVP-1203 compared to those of a single administration of 100 mg aceclofenac in patients with acute LBP and muscle spasms. PATIENTS AND METHODS: Overall, 455 patients with acute LBP and muscle spasms were enrolled. The patients were assigned to NVP-1203 or Airtal group (aceclofenac 100 mg). The primary efficacy endpoint was the mean change in the 100 mm pain movement and resting visual analog scale (VAS) scores on treatment day 7. RESULTS: The mean change in the 100 mm pain movement/resting VAS scores from baseline to day 7 was -49.7 ± 21.5/-41.0 ± 19.4 mm and -38.8 ± 18.9/-33.8 ± 18.0 mm for the NVP-1203 and Airtal groups, respectively. The differences between the two groups were statistically significant (movement, p < 0.0001; resting, p = 0.0002). Differences in least-square (LS) mean change of the 100 mm pain movement/resting VAS score between the two groups using the analysis of covariance (ANCOVA) model was -10.2/-7.4 mm, and the upper limit of the 95% confidence interval was -6.44/-4.16 mm. CONCLUSIONS: NVP-1203 is more effective in reducing pain than the 100 mg aceclofenac alone. However, the two drugs have similar safety profiles in patients with acute LBP and muscle spasms.