Amid revolutionary changes in toxicity assessment brought about by increasing regulation of chemicals, adverse outcome pathways (AOPs) have emerged as a useful framework to assess adverse effect of chemicals using molecular level effect, which aid in setting environmental regulation policies. AOPs are biological maps that describe mechanisms linking molecular initiating event to adverse outcomes (AOs) at an individual level. Each AOP consists of a molecular initiating event, key events, and an AO. AOPs use molecular markers to predict endpoints currently used in risk assessment, promote alternatives to animal model-based test methods, and provide scientific explanations for the effects of chemical exposures. Moreover, AOPs enhance certainty in interpreting existing and new information. The application of AOPs in chemical toxicity testing will help shift the existing paradigm of chemical management based on apical endpoints toward active application of in silico and in vitro data.
Animals ; Computer Simulation ; In Vitro Techniques ; Risk Assessment ; Toxicity Tests*

Amid revolutionary changes in toxicity assessment brought about by increasing regulation of chemicals, adverse outcome pathways (AOPs) have emerged as a useful framework to assess adverse effect of chemicals using molecular level effect, which aid in setting environmental regulation policies. AOPs are biological maps that describe mechanisms linking molecular initiating event to adverse outcomes (AOs) at an individual level. Each AOP consists of a molecular initiating event, key events, and an AO. AOPs use molecular markers to predict endpoints currently used in risk assessment, promote alternatives to animal model-based test methods, and provide scientific explanations for the effects of chemical exposures. Moreover, AOPs enhance certainty in interpreting existing and new information. The application of AOPs in chemical toxicity testing will help shift the existing paradigm of chemical management based on apical endpoints toward active application of in silico and in vitro data.
Animals ; Computer Simulation ; In Vitro Techniques ; Risk Assessment ; Toxicity Tests

Purpose: This study is intended to investigate the impact of an early intervention and follow-up program involving self-help groups on maternal parenting stress, depression, and parenting efficacy in families with premature infants. Methods: The study included 30 mothers in the experimental group and 29 in the control group, all of whom had premature infants in the neonatal intensive care unit. Changes in dependent variables before and after the followup program were analyzed using paired t-tests with mean and standard deviation, and variables that differed in presurvey scores were analyzed using analysis of covariance with covariates. Results: Parenting stress decreased in the experimental group that participated in the follow-up program, while it increased in the control group. Depression decreased by 3.44 points in the intervention group and 1.76 points in the control group. Parenting efficacy increased by 3.03 points in the experimental group and decreased by 1.03 points in the control group after the program. Conclusion This study highlights the significance of offering family-centered early interventions within existing hospitals or institutions, rather than relying solely on home visits, to promptly address the early developmental issues of premature infants, share information, and provide emotional support through regular self-help meetings.

OBJECTIVES: Effects of nanoparticles including zinc oxide nanoparticles, titanium oxide nanoparticles, and their mixtures on skin corrosion and irritation were investigated by using in vitro 3D human skin models (KeraSkin(TM)) and the results were compared to those of an in vivo animal test. METHODS: Skin models were incubated with nanoparticles for a definite time period and cell viability was measured by the 3-(4, 5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide method. Skin corrosion and irritation were identified by the decreased viability based on the pre-determined threshold. RESULTS: Cell viability after exposure to nanomaterial was not decreased to the pre-determined threshold level, which was 15% after 60 minutes exposure in corrosion test and 50% after 45 minutes exposure in the irritation test. IL-1alpha release and histopathological findings support the results of cell viability test. In vivo test using rabbits also showed non-corrosive and non-irritant results. CONCLUSIONS: The findings provide the evidence that zinc oxide nanoparticles, titanium oxide nanoparticles and their mixture are 'non corrosive' and 'non-irritant' to the human skin by a globally harmonized classification system. In vivo test using animals can be replaced by an alternative in vitro test.
Animals ; Cell Survival ; Classification ; Corrosion* ; Humans ; Nanoparticles* ; Nanostructures ; Rabbits ; Skin* ; Titanium ; Zinc Oxide

OBJECTIVES: In this study, we investigated the potential harmful effect of the exposure to silicon dioxide (SiO2) nanoparticles through in vitro toxicity assay using human bronchial epithelial cell, Beas-2B with a focus on the involvement of oxidative stress as the toxic mechanism. METHODS: SiO2-induced oxidative stress was assessed by examining formation of reactive oxygen species (ROS), the induction of superoxide dismutase (SOD) and heme oxygenase-1 (HO-1), as well as cytotoxicity effect was evaluation by cell viability. Subsequently, to understand the molecular mechanism of nanoparticle-induced oxidative stress, the involvement of oxidative stress-responding transcription factors, such as, nuclear factor-kappaB (NF-kappaB) and nuclear factor-E2-related factor-2 (Nrf-2), and mitogen-activated protein (MAP) kinase signal transduction pathway was also investigated. RESULTS: 5-d i phenyltera zolium bromide (MTT) assay results show that decrease 20% in cell viability and the number of cells in the subG1 phase increased. The increase in ROS formation was observed in SiO2 nanoparticle treated cells. The expression of SOD protein was not changed, whereas that of HO-1 was increased by SiO2 nanoparticle exposure. transcription factors Nrf-2 and the expression of phosphorylated form of extracellular signal-regulating kinase (ERK) was strongly induced by SiO2 nanoparticle exposure. CONCLUSIONS: SiO2 nanoparticles exert their toxicity through oxidative stress as they cause the significant increase ROS level. SiO2 nanoparticles induce induction of HO-1 via Nrf-2-ERK MAP kinase pathway. Our tested oxidative stress parameters are rather limited in terms of allowing the full understanding of oxidative stress and cellular response by SiO2 nanoparticle exposure.
Cell Survival ; Epithelial Cells ; Heme Oxygenase-1 ; Humans ; Nanoparticles ; Oxidative Stress ; Phosphotransferases ; Reactive Oxygen Species ; Signal Transduction ; Silicon Dioxide ; Superoxide Dismutase ; Transcription Factors

The source position and source dwelling time in a given source arrangement in the applicators is very high effect to determine the expose time which in general is derived from the brachytherapy planning system. In high dose rate (HDR) intracavitary radiation therapy (ICRT), the treatment is often performed in based out-patient during the whole fractionation irradiations. However, the patient should be waited on coutch for ICR treatment in first start fraction as unconvinent and immobilized state until perform the dose plannings. In our experiments, the HDR source contributed dose for 55.89+/-4.20% for straight tandem source, 38.14+/-4.46% for the right ovoid soucre on the fornix and 5.97+/-0.50% for left ovoid source. It also showed the 60.33+/-6.53% for the tandem, 33.10+/-6.74% for right ovoid and 6.58+/-0.30% for the left ovoid source in 10 degrees of applicator. The authors designed the source template dose planning software for ICRT of uterine cervix results average -0.55+/-2.15% discrepancy of the full charged brachytherapy dose planning. Developed Source temperate ICRT plaanning software guide a minimized the complains and operating times within a +/-3% of dose discrepancies.
Brachytherapy ; Cervix Uteri ; Female ; Humans ; Outpatients

PURPOSE: Mothers who give birth prematurely experience parenting stress after their babies are discharged and find it difficult to emotionally bond with them. Forming an emotional bond with a baby promotes the baby's growth and development, helps the mother cope with parenting stress after discharge, and is important for maintaining family functioning. This study aimed to identify the attachment experiences of mothers with low-birth-weight infants (LBWIs) in a follow-up program using early intervention. METHODS: A phenomenological perspective was used for this qualitative research. Data were collected from in-depth interviews with twelve mothers who participated in a follow-up program using early intervention for mothers with LBWIs from September 2017 to December 2017. Colaizzi's method was used to analyze the data. RESULTS: The experience of mothers' attachment was investigated on the basis of three categories: ‘beginning of changes in parenting methods,’ ‘forming an intimate mother–child bond,’ and ‘concerns and expectation about the child's development.’ CONCLUSION: The results indicate that the follow-up program using an early intervention designed to increase mothers' confidence in their parenting skills can promote mother' attachment and the quality of life of families with LBWIs.
Early Intervention (Education) ; Follow-Up Studies ; Growth and Development ; Humans ; Infant, Low Birth Weight ; Infant, Newborn ; Methods ; Mothers ; Object Attachment ; Parenting ; Parents ; Parturition ; Qualitative Research ; Quality of Life

Paclitaxel (taxol) has long been used as a potent anticancer agent for the treatment of many cancers. Ever since the fungal species Taxomyces andreanae was first shown to produce taxol in 1993, many endophytic fungal species have been recognized as taxol accumulators. In this study, we analyzed the taxol-producing capacity of different Colletotrichum spp. to determine the distribution of a taxol biosynthetic gene within this genus. Distribution of the taxadiene synthase (TS) gene, which cyclizes geranylgeranyl diphosphate to produce taxadiene, was analyzed in 12 Colletotrichum spp., of which 8 were found to contain the unique skeletal core structure of paclitaxel. However, distribution of the gene was not limited to closely related species. The production of taxol by Colletotrichum dematium, which causes pepper anthracnose, depended on the method in which the fungus was stored, with the highest production being in samples stored under mineral oil. Based on its distribution among Colletotrichum spp., the TS gene was either integrated into or deleted from the bacterial genome in a species-specific manner. In addition to their taxol-producing capacity, the simple genome structure and easy gene manipulation of these endophytic fungal species make them valuable resources for identifying genes in the taxol biosynthetic pathway.
Biosynthetic Pathways ; Colletotrichum* ; Fungi ; Gene Transfer, Horizontal ; Genome ; Genome, Bacterial ; Methods ; Mineral Oil ; Paclitaxel*

Clozapine is accepted as the “gold standard” antipsychotics for treatment-resistant schizophrenia. Clozapine rarely causes extrapyramidal syndrome and tardive dyskinesia, which are common with other antipsychotics, and only a transient elevation of hyperprolactinemia has been reported. Despite such clinical usefulness, there are limitations to the use of clozapine due to adverse drug reactions (ADR). Fever is a common in adverse drug reactions associated with clozapine. At initiation of clozapine most fatal ADR such as agranulocytosis and neuroleptic malignant syndrome associated with fever, in which case clozapine should be discontinued immediately. However, as benign causes of fever are much more frequent than life-threatening ADR, clozapine should not be discontinued unconditionally in the event of fever during clozapine initiation. In addition, fever may occur at any time during the maintenance of clozapine treatment. In particular, since the risk of pneumonia does not decrease over time, and clozapine has a higher risk of pneumonia than other antipsychotic drugs, it is recommended to adjust clozapine dosage through therapeutic drug monitoring.

Objectives: Agent Orange is a defoliant chemical that is widely known for its use by the U.S. military during the Vietnam War. It is known to be associated with the occurrence of various diseases in exposed subjects. However, few previous studies have focused on the effects of exposure to Agent Orange on cognitive dysfunction. Methods: A total of 387 male subjects participated in the study. They were divided into those who were exposed to Agent Orange (n=301) and those without exposure (n=86). Both were evaluated with neuropsychological batteries, including the Consortium to Establish a Registry for Alzheimer’s Disease and the Seoul Neuropsychological Screening Battery-Second Edition. Results: The group exposed to Agent Orange showed significantly higher scores in the Rey Complex Figure Test copy and recognition compared to those without exposure. Conclusion In this study, we compared the effects of exposure to Agent Orange on cognitive function in groups that had not yet progressed to dementia. The Agent Orange exposure group showed better results in some tests evaluating visuospatial and memory function.