Effect of a Follow-up Program Involving an Early Intervention and Self-help Group on Parenting Stress, Depression, and Parenting Efficacy for Mothers of Premature Infants

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.

A Review on the Cause of Fever During Clozapine Treatment / 정신신체의학

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.

Comparisons of Neuropsychological Characteristics of Elderly Subjects With Versus Without History of Agent Orange Exposure / 신경정신의학

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.

Sulfuretin Prevents Obesity and Metabolic Diseases in Diet Induced Obese Mice

The global obesity epidemic and associated metabolic diseases require alternative biological targets for new therapeutic strategies. In this study, we show that a phytochemical sulfuretin suppressed adipocyte differentiation of preadipocytes and administration of sulfuretin to high fat diet-fed obese mice prevented obesity and increased insulin sensitivity. These effects were associated with a suppressed expression of inflammatory markers, induced expression of adiponectin, and increased levels of phosphorylated ERK and AKT. To elucidate the molecular mechanism of sulfuretin in adipocytes, we performed microarray analysis and identified activating transcription factor 3 (Atf3) as a sulfuretin-responsive gene. Sulfuretin elevated Atf3 mRNA and protein levels in white adipose tissue and adipocytes. Consistently, deficiency of Atf3 promoted lipid accumulation and the expression of adipocyte markers. Sulfuretin’s but not resveratrol’s anti-adipogenic effects were diminished in Atf3 deficient cells, indicating that Atf3 is an essential factor in the effects of sulfuretin. These results highlight the usefulness of sulfuretin as a new anti-obesity intervention for the prevention of obesity and its associated metabolic diseases.

Experiences of Mothers' Attachment in a Follow-Up Program Using Early Intervention for Low-Birth-Weight Infants

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.

Epigenetic profiling to environmental stressors in model and non-model organisms: Ecotoxicology perspective

Epigenetics, potentially heritable changes in genome function that occur without alterations to DNA sequence, is an important but understudied component of ecotoxicology studies. A wide spectrum of environmental challenge, such as temperature, stress, diet, toxic chemicals, are known to impact on epigenetic regulatory mechanisms. Although the role of epigenetic factors in certain biological processes, such as tumourigenesis, has been heavily investigated, in ecotoxicology field, epigenetics still have attracted little attention. In ecotoxicology, potential role of epigenetics in multi- and transgenerational phenomenon to environmental stressors needs to be unrevealed. Natural variation in the epigenetic profiles of species in responses to environmental stressors, nature of dose-response relationships for epigenetic effects, and how to incorporate this information into ecological risk assessment should also require attentions. In this review, we presented the available information on epigenetics in ecotoxicological context. For this, we have conducted a systemic review on epigenetic profiling in response to environmental stressors, mostly chemical exposure, in model organisms, as well as, in ecotoxicologically relevant wildlife species.

Use of adverse outcome pathways in chemical toxicity testing: potential advantages and limitations

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.

Epigenetic profiling to environmental stressors in model and non-model organisms: Ecotoxicology perspective

Epigenetics, potentially heritable changes in genome function that occur without alterations to DNA sequence, is an important but understudied component of ecotoxicology studies. A wide spectrum of environmental challenge, such as temperature, stress, diet, toxic chemicals, are known to impact on epigenetic regulatory mechanisms. Although the role of epigenetic factors in certain biological processes, such as tumourigenesis, has been heavily investigated, in ecotoxicology field, epigenetics still have attracted little attention. In ecotoxicology, potential role of epigenetics in multi- and transgenerational phenomenon to environmental stressors needs to be unrevealed. Natural variation in the epigenetic profiles of species in responses to environmental stressors, nature of dose-response relationships for epigenetic effects, and how to incorporate this information into ecological risk assessment should also require attentions. In this review, we presented the available information on epigenetics in ecotoxicological context. For this, we have conducted a systemic review on epigenetic profiling in response to environmental stressors, mostly chemical exposure, in model organisms, as well as, in ecotoxicologically relevant wildlife species.

Use of adverse outcome pathways in chemical toxicity testing: potential advantages and limitations

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.

Systematic Analysis of the Anticancer Agent Taxol-Producing Capacity in Colletotrichum Species and Use of the Species for Taxol Production

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.

Screening of toxic potential of graphene family nanomaterials using in vitro and alternative in vivo toxicity testing systems

OBJECTIVES: The widely promising applications of graphene nanomaterials raise considerable concerns regarding their environmental and human health risk assessment. The aim of the current study was to evaluate the toxicity profiling of graphene family nananomaterials (GFNs) in alternative in vitro and in vivo toxicity testing models. METHODS: The GFNs used in this study are graphene nanoplatelets ([GNPs]-pristine, carboxylate [COOH] and amide [NH2]) and graphene oxides (single layer [SLGO] and few layers [FLGO]). The human bronchial epithelial cells (Beas2B cells) as in vitro system and the nematode Caenorhabditis elegans as in vivo system were used to profile the toxicity response of GFNs. Cytotoxicity assays, colony formation assay for cellular toxicity and reproduction potentiality in C. elegans were used as end points to evaluate the GFNs' toxicity. RESULTS: In general, GNPs exhibited higher toxicity than GOs in Beas2B cells, and among the GNPs the order of toxicity was pristine>NH2>COOH. Although the order of toxicity of the GNPs was maintained in C. elegans reproductive toxicity, but GOs were found to be more toxic in the worms than GNPs. In both systems, SLGO exhibited profoundly greater dose dependency than FLGO. The possible reason of their differential toxicity lay in their distinctive physicochemical characteristics and agglomeration behavior in the exposure media. CONCLUSIONS: The present study revealed that the toxicity of GFNs is dependent on the graphene nanomaterial's physical forms, surface functionalizations, number of layers, dose, time of exposure and obviously, on the alternative model systems used for toxicity assessment.

Screening of toxic potential of graphene family nanomaterials using in vitro and alternative in vivo toxicity testing systems

OBJECTIVES: The widely promising applications of graphene nanomaterials raise considerable concerns regarding their environmental and human health risk assessment. The aim of the current study was to evaluate the toxicity profiling of graphene family nananomaterials (GFNs) in alternative in vitro and in vivo toxicity testing models. METHODS: The GFNs used in this study are graphene nanoplatelets ([GNPs]-pristine, carboxylate [COOH] and amide [NH2]) and graphene oxides (single layer [SLGO] and few layers [FLGO]). The human bronchial epithelial cells (Beas2B cells) as in vitro system and the nematode Caenorhabditis elegans as in vivo system were used to profile the toxicity response of GFNs. Cytotoxicity assays, colony formation assay for cellular toxicity and reproduction potentiality in C. elegans were used as end points to evaluate the GFNs' toxicity. RESULTS: In general, GNPs exhibited higher toxicity than GOs in Beas2B cells, and among the GNPs the order of toxicity was pristine>NH2>COOH. Although the order of toxicity of the GNPs was maintained in C. elegans reproductive toxicity, but GOs were found to be more toxic in the worms than GNPs. In both systems, SLGO exhibited profoundly greater dose dependency than FLGO. The possible reason of their differential toxicity lay in their distinctive physicochemical characteristics and agglomeration behavior in the exposure media. CONCLUSIONS: The present study revealed that the toxicity of GFNs is dependent on the graphene nanomaterial's physical forms, surface functionalizations, number of layers, dose, time of exposure and obviously, on the alternative model systems used for toxicity assessment.

Effect of aspect ratio on the uptake and toxicity of hydroxylated-multi walled carbon nanotubes in the nematode, Caenorhabditis elegans

OBJECTIVES: In this study, the effect of tube length and outer diameter (OD) size of hydroxylated-multi walled carbon nanotubes (OH-MWCNTs) on their uptake and toxicity was investigated in the nematode Caenorhabditis elegans using a functional mutant analysis. METHODS: The physicochemical properties of three different OH-MWCNTs were characterized. Uptake and toxicity were subsequently investigated on C. elegans exposed to MWCNTs with different ODs and tube lengths. RESULTS: The results of mutant analysis suggest that ingestion is the main route of MWCNTs uptake. We found that OH-MWCNTs with smaller ODs were more toxic than those with larger ODs, and OH-MWCNTs with shorter tube lengths were more toxic than longer counterparts to C. elegans. CONCLUSIONS: Overall the results suggest the aspect ratio affects the toxicity of MWCNTs in C. elegans. Further thorough study on the relationship between physicochemical properties and toxicity needs to be conducted for more comprehensive understanding of the uptake and toxicity of MWCNTs.

Effect of aspect ratio on the uptake and toxicity of hydroxylated-multi walled carbon nanotubes in the nematode, Caenorhabditis elegans

OBJECTIVES: In this study, the effect of tube length and outer diameter (OD) size of hydroxylated-multi walled carbon nanotubes (OH-MWCNTs) on their uptake and toxicity was investigated in the nematode Caenorhabditis elegans using a functional mutant analysis. METHODS: The physicochemical properties of three different OH-MWCNTs were characterized. Uptake and toxicity were subsequently investigated on C. elegans exposed to MWCNTs with different ODs and tube lengths. RESULTS: The results of mutant analysis suggest that ingestion is the main route of MWCNTs uptake. We found that OH-MWCNTs with smaller ODs were more toxic than those with larger ODs, and OH-MWCNTs with shorter tube lengths were more toxic than longer counterparts to C. elegans. CONCLUSIONS: Overall the results suggest the aspect ratio affects the toxicity of MWCNTs in C. elegans. Further thorough study on the relationship between physicochemical properties and toxicity needs to be conducted for more comprehensive understanding of the uptake and toxicity of MWCNTs.

Skin corrosion and irritation test of sunscreen nanoparticles using reconstructed 3D human skin model

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.

Involvement of Caenohabditis elegans MAPK Signaling Pathways in Oxidative Stress Response Induced by Silver Nanoparticles Exposure

In the present study, toxicity of silver nanoparticles (AgNPs) was investigated in the nematode, Caenohabditis elegans focusing on the upstream signaling pathway responsible for regulating oxidative stress, such as mitogen-activated protein kinase (MAPK) cascades. Formation of reactive oxygen species (ROS) was observed in AgNPs exposed C. elegans, suggesting oxidative stress as an important mechanism in the toxicity of AgNPs towards C. elegans. Expression of genes in MAPK signaling pathways increased by AgNPs exposure in less than 2-fold compared to the control in wildtype C. elegans, however, those were increased dramatically in sod-3 (gk235) mutant after 48 h exposure of AgNPs (i.e. 4-fold for jnk-1 and mpk-2; 6-fold for nsy-1, sek-1, and pmk-1, and 10-fold for jkk-1). These results on the expression of oxidative stress response genes suggest that sod-3 gene expression appears to be dependent on p38 MAPK activation. The high expressions of the pmk-1 gene 48 h exposure to AgNPs in the sod-3 (gk235) mutant can also be interpreted as compensatory mechanisms in the absence of important stress response genes. Overall results suggest that MAPK-based integrated stress signaling network seems to be involved in defense to AgNPs exposure in C.elegans.

Maintaining the Constant Exposure Condition for an Acute Caenorhabditis elegans Mortality Test Using Passive Dosing

OBJECTIVES: Maintaining the constant exposure to hydrophobic organic compouds in acute toxicity tests is one of the most difficult issues in the evaluation of their toxicity and corresponding risks. Passive dosing is an emerging tool to keep constant aqueous concentration because of the overwhelming mass loaded in the dosing phase. The primary objectives of this study were to develop the constant exposure condition for an acute mortality test and to compare the performance of the passive dosing method with the conventional spiking with co-solvent. METHODS: A custom cut polydimethylsiloxane (PDMS) tubing loaded with benzyl butyl phthalate (BBP) was placed in each well of a 24-well plate containing assay medium. The rate of the release of BBP from PDMS was evaluated by measuring the change in the concentration of BBP in the assay medium. The efficiency of maintaining constant exposure condition was also evaluated using a simple two-compartment mass transport model employing a film-diffusion theory. An acute mortality test using 10 C. elegans in each well was conducted for the evaluation of the validity of passive dosing and the comparative evaluation of the passive dosing method and the conventional spiking method. RESULTS: Free concentration in the assay medium reached 95% steady state value within 2.2 hours without test organisms, indicating that this passive dosing method is useful for an acute toxicity test in 24 hours. The measured concentration after the mortality test agreed well with the estimated values from partitioning between PDMS and the assay medium. However, the difference between the nominal and the free concentration became larger as the spiked concentration approached water solubility, indicating the instability of the conventional spiking with a co-solvent. CONCLUSIONS: The results in this study support that passive dosing provides a stable exposure condition for an acute toxicity test. Thus, it is likely that more reliable toxicity assessment can be made for hydrophobic chemicals using passive dosing.

SiO2 Nanoparticles Induced Cytotoxicity by Oxidative Stress in Human Bronchial Epithelial Cell, Beas-2B

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.

Analyses of Expressed Sequence Tags from of Chironomus riparius Using Pyrosequencing : Molecular Ecotoxicology Perspective

OBJECTIVES: Chironomus riparius, a non-biting midge (Chironomidae, Diptera), is extensively used as a model organism in aquatic ecotoxicological studies, and considering the potential of C. riparius larvae as a bio-monitoring species, little is known about its genome sequences. This study reports the results of an Expressed Sequence Tags (ESTs) sequencing project conducted on C. riparius larvae using 454 pyrosequencing. METHODS: To gain a better understanding of C. riparius transcriptome, we generated ESTs database of C. ripairus using pyrosequencing method. RESULTS: Sequencing runs, using normalized cDNA collections from fourth instar larvae, yielded 20,020 expressed sequence tags, which were assembled into 8,565 contigs and 11,455 singletons. Sequence analysis was performed by BlastX search against the National Center for Biotechnology Information (NCBI) nucleotide (nr) and uniprot protein database. Based on the gene ontology classifications, 24% (E-value < or =1(-5)) of the sequences had known gene functions, 24% had unknown functions and 52% of sequences did not match any known sequences in the existing database. Sequence comparison revealed 81% of the genes have homologous genes among other insects belonging to the order Diptera providing tools for comparative genome analyses. Targeted searches using these annotations identified genes associated with essential metabolic pathways, signaling pathways, detoxification of toxic metabolites and stress response genes of ecotoxicological interest. CONCLUSIONS: The results obtained from this study would eventually make ecotoxicogenomics possible in a truly environmentally relevant species, such as, C. riparius.