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Conflicting findings have been reported regarding the association between Agent Orange (AO) exposure and type 2 diabetes. This study aimed to examine whether AO exposure is associated with the development of type 2 diabetes and to verify the causal relationship between AO exposure and type 2 diabetes by combining DNA methylation with DNA genotype analyses. An epigenome-wide association study and DNA genotype analyses of the blood of AO-exposed and AO-unexposed individuals with type 2 diabetes and that of healthy controls were performed. Methylation quantitative trait locus and Mendelian randomisation analyses were performed to evaluate the causal effect of AO-exposure-identified CpGs on type 2 diabetes. AO-exposed individuals with type 2 diabetes were associated with six hypermethylated CpG sites (cg20075319, cg21757266, cg05203217, cg20102280, cg26081717, and cg21878650) and one hypo-methylated CpG site (cg07553761). Methylation quantitative trait locus analysis showed the methylation levels of some CpG sites (cg20075319, cg20102280, and cg26081717) to be significantly different. Mendelian randomisation analysis showed that CpG sites that were differentially methylated in AO-exposed individuals were causally associated with type 2 diabetes; the reverse causal effect was not significant. These findings reflect the need for further epigenetic studies on the causal relationship between AO exposure and type 2 diabetes.
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Agente Naranja , Metilación de ADN , Diabetes Mellitus Tipo 2 , Epigénesis Genética , Veteranos , Humanos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/inducido químicamente , Masculino , República de Corea/epidemiología , Persona de Mediana Edad , Islas de CpG , Femenino , Estudio de Asociación del Genoma Completo , Anciano , Sitios de Carácter Cuantitativo , Análisis de la Aleatorización Mendeliana , Estudios de Casos y ControlesRESUMEN
Background: Drug-induced hypersensitivity such as anaphylaxis is an important cause of drug-related morbidity and mortality. Cefaclor is a leading cause of drug induced type I hypersensitivity in Korea, but little is yet known about genetic biomarkers to predict this hypersensitivity reaction. We aimed to evaluate the possible involvement of genes in cefaclor induced type I hypersensitivity. Methods: Whole exome sequencing (WES) and HLA genotyping were performed in 43 patients with cefaclor induced type I hypersensitivity. In addition, homology modeling was performed to identify the binding forms of cefaclor to HLA site. Results: Anaphylaxis was the most common phenotype of cefaclor hypersensitivity (90.69%). WES results show that rs62242177 and rs62242178 located in LIMD1 region were genome-wide significant at the 5 × 10-8 significance level. Cefaclor induced type I hypersensitivity was significantly associated with HLA-DRB1∗04:03 (OR 4.61 [95% CI 1.51-14.09], P < 0.002) and HLA-DRB1∗14:54 (OR 3.86 [95% CI 1.09-13.67], P < 0.002). Conclusion: LIMD1, HLA-DRB1∗04:03 and HLA-DRB1∗14:54 may affect susceptibility to cefaclor induced type I hypersensitivity. Further confirmative studies with a larger patient population should be performed to ascertain the role of HLA-DRB1 and LIMD1 in the development of cefaclor induced hypersensitivity.
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The reluctance of parents to vaccinate their children against COVID-19 was prevalent particularly when uncertainty over vaccination outcomes prevailed. We conducted a nationwide randomized online survey experiment to assess the effect of information provision on parental intention for COVID-19 vaccination before the government started vaccination for children in South Korea. Parents of elementary school children were provided with either no information (Control), information on vaccine profile (vaccine informed group; VI), or COVID-19 (disease informed group; DI). Among 359,110 participants, parental intention for vaccination of children was significantly higher in both VI and DI groups compared with the Control group. In terms of effect size, information on COVID-19 vaccine increased likelihood to vaccinate by 1620 per 100,000 parents and reduced vaccine hesitancy by 1340 per 100,000 parents. Consistently with the positive effect on vaccination intention, both VI and DI interventions increased participants' perceptions on vaccination benefits being higher than its risks and vaccination risks being lower than health risks of COVID-19 infection, and self-reported trust in COVID-19 information. Our results lend strong support to the claim that the provision of targeted, tailored information on COVID-19 vaccine and infection increases parental intention to vaccinate children and reduces vaccine hesitancy.
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Vacunas contra la COVID-19 , COVID-19 , Niño , Humanos , Intención , COVID-19/epidemiología , COVID-19/prevención & control , Vacunación , PadresRESUMEN
In radiomics research, the issue of different instruments being used is significant. In this study, we compared three correction methods to reduce the batch effects in radiogenomic data from fluorodeoxyglucose (FDG) PET/CT images of lung cancer patients. Texture features of the FDG PET/CT images and genomic data were retrospectively obtained. The features were corrected with different methods: phantom correction, ComBat method, and Limma method. Batch effects were estimated using three analytic tools: principal component analysis (PCA), the k-nearest neighbor batch effect test (kBET), and the silhouette score. Finally, the associations of features and gene mutations were compared between each correction method. Although the kBET rejection rate and silhouette score were lower in the phantom-corrected data than in the uncorrected data, a PCA plot showed a similar variance. ComBat and Limma methods provided correction with low batch effects, and there was no significant difference in the results of the two methods. In ComBat- and Limma-corrected data, more texture features exhibited a significant association with the TP53 mutation than in those in the phantom-corrected data. This study suggests that correction with ComBat or Limma methods can be more effective or equally as effective as the phantom method in reducing batch effects.
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Neoplasias Pulmonares , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Fluorodesoxiglucosa F18 , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/genética , Estudios Retrospectivos , Tomografía de Emisión de Positrones/métodosRESUMEN
The current investigation aimed at bimetallic gold-silver nanoparticles (Au/Ag NPs), here called BM-GS NPs, synthesis using sericin protein as the reducing agent in an easy, cost-effective, and sustainable way. The obtained BM-GS NPs were characterized by UV-Visible spectroscopy, Transmission electron microscopy (TEM), energy dispersive X-ray analysis (EDS), atomic force microscopy (AFM), Dynamic light scattering (DLS) and Zeta potential, X-ray Powder Diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and Thermogravimetric analysis followed by evaluation of its multitherapeutic and photocatalytic degradation potentials. The TEM analysis revealed its spherical nature and the EDS result displayed the presence of both Ag and Au elements, confirming the synthesis of BM-GS NPs. The XRD pattern verified the crystalline nature of the nanoparticles (NPs). The DLS analysis showed an average size of 86.08 d nm and the zeta potential showed a highly negative value (-26.3 mV) which specifies that the generated bimetallic NPs are stable. The BM-GS NPs exhibited positive wound healing potential (with 63.38% of wound closure rate at 25 µg/ml, as compared to 54.42% by the untreated control) with very negligible toxicity effect on the cell viability of the normal keratinocyte cells. It also demonstrated promising antioxidant properties with 65.00%, 69.23%, and 63.03% activity at 100 µg/ml concentration for ABTS (2, 2-azinobis) (3-ethylbenzothiazoline-6-sulfonic acid)), DPPH (1, 1 diphenyl-2-picrylhydrazyl) and SOD (superoxide dismutase enzyme) assays respectively, antidiabetic potential (with a significantly high α-glucosidase inhibition potential of 99.69% at 10µg/ml concentration and 62.11% of α-amylase enzyme inhibition at 100 µg/ml concentration) and moderate tyrosinase inhibitory potential (with 17.09% at 100 µg/ml concentration). Besides, it displayed reasonable antibacterial potential with the diameter of zone of inhibition ranging between 10.89 and 12.39 mm. Further, its antibacterial mode of action reveals that its effects could be due to being very smaller, the NPs could have penetrated inside the cellular membrane thereby causing rupture and damage to the interior materials leading to cellular lysis. The photocatalytic evaluation showed that synthesized BM-GS NPs have the efficiency of degrading methylene blue dye by 34.70% within 3 h of treatment. The above findings revealed the multi-therapeutic efficacy of the sericin globular protein-mediated BM-GS NPs and its potential future applications in the cosmetics and food sector and environmental contamination management industries.
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Nanopartículas del Metal , Sericinas , Espectroscopía Infrarroja por Transformada de Fourier , Plata/química , Nanopartículas del Metal/toxicidad , Nanopartículas del Metal/química , Oro/química , Antibacterianos/farmacología , Antibacterianos/químicaRESUMEN
There is growing concern about the use of plastic in packaging for food materials, as this results in increased plastic waste materials in the environment. To counter this, alternative sources of packaging materials that are natural and based on eco-friendly materials and proteins have been widely investigated for their potential application in food packaging and other industries of the food sector. Sericin, a silk protein that is usually discarded in large quantities by the sericulture and textile industries during the degumming process of manufacturing silk from silk cocoons, can be explored for its application in food packaging and in other food sectors as a functional food and component of food items. Hence, its repurposing can result in reduced economic costs and environmental waste. Sericin extracted from silk cocoon possesses several useful amino acids, such as aspartic acid, glycine, and serine. Likewise, sericin is strongly hydrophilic, a property that confers effective biological and biocompatible characteristics, including antibacterial, antioxidant, anticancer, and anti-tyrosinase properties. When used in combination with other biomaterials, sericin has proved to be effective in the manufacture of films or coating or packaging materials. In this review, the characteristics of sericin materials and their potential application in food-sector industries are discussed in detail.
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Bombyx , Sericinas , Animales , Sericinas/química , Seda/química , Materiales Biocompatibles/química , Monofenol Monooxigenasa/metabolismo , Industria de Alimentos , Bombyx/metabolismoRESUMEN
BACKGROUND: The pathogenesis of diabetic kidney disease (DKD) is complex, involving metabolic and hemodynamic factors. Although DKD has been established as a heritable disorder and several genetic studies have been conducted, the identification of unique genetic variants for DKD is limited by its multiplex classification based on the phenotypes of diabetes mellitus (DM) and chronic kidney disease (CKD). Thus, we aimed to identify the genetic variants related to DKD that differentiate it from type 2 DM and CKD. METHODS: We conducted a large-scale genome-wide association study mega-analysis, combining Korean multi-cohorts using multinomial logistic regression. A total of 33,879 patients were classified into four groups-normal, DM without CKD, CKD without DM, and DKD-and were further analyzed to identify novel single-nucleotide polymorphisms (SNPs) associated with DKD. Additionally, fine-mapping analysis was conducted to investigate whether the variants of interest contribute to a trait. Conditional analyses adjusting for the effect of type 1 DM (T1D)-associated HLA variants were also performed to remove confounding factors of genetic association with T1D. Moreover, analysis of expression quantitative trait loci (eQTL) was performed using the Genotype-Tissue Expression project. Differentially expressed genes (DEGs) were analyzed using the Gene Expression Omnibus database (GSE30529). The significant eQTL DEGs were used to explore the predicted interaction networks using search tools for the retrieval of interacting genes and proteins. RESULTS: We identified three novel SNPs [rs3128852 (P = 8.21×10-25), rs117744700 (P = 8.28×10-10), and rs28366355 (P = 2.04×10-8)] associated with DKD. Moreover, the fine-mapping study validated the causal relationship between rs3128852 and DKD. rs3128852 is an eQTL for TRIM27 in whole blood tissues and HLA-A in adipose-subcutaneous tissues. rs28366355 is an eQTL for HLA-group genes present in most tissues. CONCLUSIONS: We successfully identified SNPs (rs3128852, rs117744700, and rs28366355) associated with DKD and verified the causal association between rs3128852 and DKD. According to the in silico analysis, TRIM27 and HLA-A can define DKD pathophysiology and are associated with immune response and autophagy. However, further research is necessary to understand the mechanism of immunity and autophagy in the pathophysiology of DKD and to prevent and treat DKD.
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Diabetes Mellitus Tipo 1 , Nefropatías Diabéticas , Insuficiencia Renal Crónica , Humanos , Nefropatías Diabéticas/genética , Estudio de Asociación del Genoma Completo , Predisposición Genética a la Enfermedad/genética , República de Corea/epidemiología , Antígenos HLA-A/genética , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Introduction: A number of biological wastes and factory waste materials have been tested recently for the eco-friendly biosynthesis of nanoparticles. Sericin protein (SSP) is usually removed from the silk cocoon during the degumming process in the process of making the silk, and this sericin protein is normally thrown away by the sericulture industries as waste materials. It is found that this sericin protein possesses a number of biological properties. Methods: Considering this, in the present study, an effort has been made to biosynthesize gold nanoparticles (SSP-AuNPs) using the waste sericin solution as the reducing and capping agent and investigate its biopotential in terms of its wound healing, antioxidant and antibacterial activities. Results: The synthesis of SSP-AuNPs was perceived by the visual color change and confirmed by UV-Vis spectroscopy with absorption maxima at 522 nm. Further characterization of SSP-AuNPs was done by TEM, EDS, XRD, FTIR, DLS, zeta potential, TGA, AFM, etc. The size of SSP-AuNPs was found out to be 54.82 nm as per the particle size analyzer and the zeta potential is -19.8 mV. The SSP-AuNPs displayed promising wound healing potential of 70.96 and 69.76% wound closure rate at 5 and 10 µg/mL respectively as compared to 74.91% by the Centella asiatica taken as a positive control. It also exhibited promising antioxidant potential in terms of the DPPH, ABTS free radical scavenging, reducing power potential, and total antioxidant capacity. Besides, the SSP-AuNPs also displayed significant antibacterial activities against the tested pathogenic bacterial with the diameter of inhibition zones ranging between 12.10 and 14.96 mm as compared to the positive control cephalexin that displayed inhibition zones ranging between 12.08 and 13.24 mm. Discussion: Taken together, SSP-AuNPs could serve as an interesting candidate for food, cosmetics, and biomedical fields in the applications of wound healing, cosmetics, antibacterial bandages, and ointments, etc.
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Bombyx , Nanopartículas del Metal , Sericinas , Animales , Seda/química , Antioxidantes/farmacología , Antioxidantes/química , Sericinas/química , Sericinas/farmacología , Bombyx/química , Oro/química , Nanopartículas del Metal/química , Antibacterianos/farmacología , Antibacterianos/química , Cicatrización de HeridasRESUMEN
Hexachlorobutadiene (HCBD) is a persistent organic pollutant (POP), and a toxin whose primary target organ is the kidney. Consequently, quantifying the amount of HCBD in food is essential for determining whether it poses a health risk. The current study established and validated an analytical method for assessing HCBD in food using gas chromatography/mass spectrometry (GC/MS). Subsequently, we conducted for the first time a risk assessment of HCBD through Korean food consumption. The ranges of HCBD concentration in 595 food samples were as follows: not detectable (nd)-0.947 ng/g for agricultural products, nd-0.920 ng/g for animal products, nd-1.323 ng/g for fishery products and nd-1.081 ng/g for processed food products. The daily intakes of HCBD for the general population were 0.22 ng/kg body weight (b.w.)/day for agricultural products, 0.30 ng/kg b.w./day for animal products, 0.07 ng/kg b.w./day for fishery products and 0.33 ng/kg b.w./day for processed food products. These exposure levels are below the tolerable daily intake (TDI, 2 µg/kg body weight/day) established by the National Institute of Food and Drug Safety Evaluation (NiFDS) in the Republic of Korea. Taking into account the risk index of 0.011%, we can, therefore, conclude that there are no health concerns for the Korean population.
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Agricultura , Butadienos , Animales , Humanos , Dieta , Medición de Riesgo , Contaminación de Alimentos/análisisRESUMEN
Importance: Vaccination against COVID-19 is an effective method for individuals to reduce negative health outcomes. However, widespread COVID-19 vaccination among children has been challenging owing to parental hesitancy. Objective: To examine parental decision-making in favor of the COVID-19 vaccine for their children and its association with the sufficiency and credibility of the information about the vaccine. Design, Setting, and Participants: This cross-sectional survey study was conducted in South Korea from February 7 to 10, 2022, 7 weeks before initiation of the COVID-19 vaccine for children aged 5 to 11 years. Parents were included if they spoke Korean and had at least 1 child in elementary school (grades 1-6). Parents and children were included in a 1:1 ratio; a total of 113â¯450 parents and 113â¯450 children were included in the analysis. Statistical analysis was performed between March and April 2022. Main Outcomes and Measures: The main outcomes of interest were (1) parental acceptance of COVID-19 vaccination for their children and (2) its association with self-reported sufficiency and credibility of information about the vaccine. A multivariable logistic regression was used to evaluate factors associated with parental decision-making in favor of COVID-19 vaccination; path analysis was used to examine indirect effects of information sufficiency and credibility. Results: Of the 113â¯450 children, 58â¯342 (51.4%) were boys, and the mean (SD) age was 10.1 (1.5) years. Of the 113â¯450 parents who responded, 7379 (6.5%) were accepting vaccination for their children; 15â¯731 (13.9%) reported the vaccine-related information they received was sufficient, and 23â¯021 (20.3%) reported the information was credible. Parents who reported that the information was sufficient were 3.08 times (95% CI, 2.85-3.33; P < .001) more likely to report being willing to vaccinate their children than those who believed the information was insufficient, and those who reported that the information was credible were 7.55 times (95% CI, 6.46-8.87; P < .001) more likely to report being willing to vaccinate their children than those who believed the information was not credible. Higher levels of information sufficiency and credibility were associated with perceptions of increased vaccine safety (sufficiency: ß = 0.08; P < .001; credibility: ß = 0.59; P < .001) and effectiveness (sufficiency: ß = 0.05; P < .001; credibility: ß = 0.60; P < .001). Conclusions and Relevance: In this study, a significant association was found between self-reported sufficiency and credibility of vaccine-related information and parental decision-making regarding COVID-19 vaccination for their children, suggesting that communications and policies that provide sound information are essential to improve vaccination rates.
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Vacunas contra la COVID-19 , COVID-19 , Masculino , Niño , Humanos , Femenino , Vacunas contra la COVID-19/uso terapéutico , Estudios Transversales , COVID-19/epidemiología , COVID-19/prevención & control , Vacunación , Padres , República de Corea/epidemiologíaRESUMEN
OBJECTIVES: Vaccination is one of the most important strategies to contain the spread of coronavirus disease 2019 (COVID-19). Vaccination in children is dependent on their parents, making it important to understand parents' awareness and attitudes toward vaccines in order to devise strategies to raise vaccination rates in children. METHODS: A web-based nationwide survey was conducted among Korean parents of 7-year-old to 18-year-old children in August 2021 to estimate parents' intention to vaccinate their children against COVID-19 and identify key factors affecting parental acceptance and hesitancy through regression analysis. RESULTS: Approximately 56.4% (575/1,019) were willing to vaccinate their children against COVID-19. Contributing factors to COVID-19 vaccine hesitancy were being a mother (adjusted odds ratio [aOR], 0.36; 95% confidence interval [CI], 0.25 to 0.52), a lower education level (aOR, 0.83; 95% CI, 0.70 to 0.97), hesitancy to other childhood vaccines (aOR, 0.78; 95% CI, 0.64 to 0.96), and refusal to vaccinate themselves (aOR, 0.08; 95% CI, 0.02 to 0.20). Having older children (aOR, 1.20; 95% CI, 1.13 to 1.28), trusting the child's doctor (aOR, 1.19; 95% CI, 1.07 to 1.32), positive perceptions of the COVID-19 vaccine's effectiveness (aOR, 2.60; 95% CI, 1.90 to 3.57) and perceiving the COVID-19 vaccine as low-risk (aOR, 1.68; 95% CI, 1.27 to 2.24) were associated with COVID-19 vaccine acceptance. Concerns about adverse reactions were the most common cause of hesitancy. CONCLUSIONS: Providing parents with accurate and reliable information on vaccine effectiveness and safety is important to increase COVID-19 vaccine uptake in children. Differential or targeted approaches to parents according to gender, age, and their children's age are necessary for effective communication about vaccination in children.
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Vacunas contra la COVID-19 , COVID-19 , Vacunas , Adolescente , Niño , Humanos , Comunicación , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Padres , República de Corea/epidemiologíaRESUMEN
Purpose: This study aimed to develop a lifestyle modification (LSM) mobile application based on the Android operating system for overweight and obese breast cancer survivors (BCS) in Korea and evaluate its usability. Methods: The content analysis, design, development, implementation, and evaluation of the LSM intervention mobile application for overweight and obese BCS was conducted by identifying survivors' needs, searching the literature, and reviewing existing mobile applications. The survey was conducted from June 1 to December 28, 2020 at Jeonju city, Korea. Results: The mobile application for BCS included dietary and exercise information, weight logs, as well as distress and daily achievement check. It also included information and videos on the prevention of breast cancer recurrence and used a communication bulletin board. Expert and user usability evaluation of its content and functions confirmed that it was appropriate and satisfactory for overweight and obese BCS. Conclusion: This LSM mobile application developed for overweight and obese BCS was found to be appropriate for use. It can be applied for further study of effectiveness on improving their health and maintaining a healthy lifestyle, to ultimately improve quality of life.
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Correction for 'Metallosupramolecules of pillar[5]-bis-trithiacrown including a mercury(ii) iodide ion-triplet complex' by Mingyeong Shin et al., Chem. Commun., 2020, DOI: 10.1039/d0cc03902k.
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A combination of pillar[5]-bis-trithiacrown (L) and mercury(ii) halides afforded a monomer complex (Cl--form), a 1-D coordination polymer (Br--form) and a supramolecular ion-triplet complex [(I·Hg·I)@L] (I--form). In the ion-triplet complex, the host encapsulates the (I--Hg2+-I-) entity via Hg2+π and C-HI- interactions, reflecting geometrical complementarity.
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Purpose: This study investigated lifestyle, depression, marital intimacy, and quality of life (QoL) in breast cancer survivors, with the goal of identifying the impacts of these factors on QoL. Methods: A sample of 146 breast cancer survivors was surveyed in this cross-sectional study. Data were collected from March 20 to May 30, 2019, using self-report structured questionnaires at a hospital located in Jeonju, Korea. Data were analyzed using the independent t-test, analysis of variance, Pearson correlation coefficients, and hierarchical regression analysis. Participants agreed to complete a face-to-face interview, including administration of the Health Promoting Lifestyle Profile II, Depression Anxiety Stress Scale 21-Depression Scale, Marital Intimacy Scale, and Functional Assessment Cancer Therapy-Breast Cancer tool. Results: QoL was positively correlated with lifestyle (r=.49, p<.001) and marital intimacy (r=.45, p<.001) and negatively correlated with depression (r=-.72, p<.001). Hierarchical multiple regression analysis showed that depression (ß=-0.63, p<.001), marital intimacy (ß=0.19, p=.001), and lifestyle (ß=0.13, p=.031) had significant effects on the QoL of breast cancer survivors, accounting for 63.3% of variance in related QoL. Conclusion: This study provides insights into how breast cancer survivors' QoL was influenced by depression, marital intimacy, and lifestyle. To improve the QoL of breast cancer survivors, healthcare providers should consider developing strategies to decrease depression, to increase marital intimacy, and to improve lifestyle.
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Usage patterns of consumer products (CP) must be determined for accurate exposure assessments. The purpose was to quantitatively estimate the uncertainty in exposure factors of CP according to various sample sizes. The uncertainty was calculated based on exposure factors of 3,333 participants representing the Korean population referred to as the 'parent population'. Small subsamples of participants randomly selected from the parent population were used to evaluate the exposure factors of 13 CPs. Exposure factors were compared with the corresponding values from the parent population. For all exposure factors, the ratio of the mean values of the 75th percentile of the subsamples to the values of the parent population became closer to 1 as the subsample size increased. For frequency of use factor, the ratio was between 0.9 and 1.1 with sample size of 100 except household bleach and trigger-type bathroom cleaner. For amount of use factor, the ratio was between 0.9 and 1.1 with sample size of 100 except body wash, household bleach, and glass cleaner. These results showed the quantitative uncertainty of exposure factor estimations according to various sample sizes. A sample size of at least 100 subjects should be collected for estimation of exposure factors for most CP.
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Cosméticos , Desinfectantes , Exposición a Riesgos Ambientales , Productos Domésticos , Incertidumbre , Humanos , República de CoreaRESUMEN
Variants in the APOE gene region may explain ethnic differences in the association of Alzheimer's disease (AD) with ε4. Ethnic differences in allele frequencies for three APOE region SNPs (single nucleotide polymorphisms) were identified and tested for association in 19,398 East Asians (EastA), including Koreans and Japanese, 15,836 European ancestry (EuroA) individuals, and 4985 African Americans, and with brain imaging measures of cortical atrophy in sub-samples of Koreans and EuroAs. Among ε4/ε4 individuals, AD risk increased substantially in a dose-dependent manner with the number of APOE promoter SNP rs405509 T alleles in EastAs (TT: OR (odds ratio) = 27.02, p = 8.80 × 10-94; GT: OR = 15.87, p = 2.62 × 10-9) and EuroAs (TT: OR = 18.13, p = 2.69 × 10-108; GT: OR = 12.63, p = 3.44 × 10-64), and rs405509-T homozygotes had a younger onset and more severe cortical atrophy than those with G-allele. Functional experiments using APOE promoter fragments demonstrated that TT lowered APOE expression in human brain and serum. The modifying effect of rs405509 genotype explained much of the ethnic variability in the AD/ε4 association, and increasing APOE expression might lower AD risk among ε4 homozygotes.
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BACKGROUND: In genetic analyses, the term 'batch effect' refers to systematic differences caused by batch heterogeneity. Controlling this unintended effect is the most important step in quality control (QC) processes that precede analyses. Currently, batch effects are not appropriately controlled by statistics, and newer approaches are required. METHODS: In this report, we propose a new method to detect the heterogeneity of probe intensities among different batches and a procedure for calling genotypes and QC in the presence of a batch effect. First, we conducted a multivariate analysis of variance (MANOVA) to test the differences in probe intensities among batches. If heterogeneity is detected, subjects should be clustered using a K-medoid algorithm using the averages of the probe intensity measurements for each batch and the genotypes of subjects in different clusters should be called separately. RESULTS: The proposed method was used to assess genotyping data of 3619 subjects consisting of 1074 patients with Alzheimer's disease, 296 with mild cognitive impairment (MCI), and 1153 controls. The proposed method improves the accuracy of called genotypes without the need to filter a lot of subjects and SNPs, and therefore is a reasonable approach for controlling batch effects. CONCLUSIONS: We proposed a new strategy that detects batch effects with probe intensity measurement and calls genotypes in the presence of batch effects. The application of the proposed method to real data shows that it produces a balanced approach. Furthermore, the proposed method can be extended to various scenarios with a simple modification.
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Estudio de Asociación del Genoma Completo/métodos , Técnicas de Genotipaje/métodos , Polimorfismo de Nucleótido Simple , Enfermedad de Alzheimer/genética , Análisis de Varianza , Disfunción Cognitiva/genética , Heterogeneidad Genética , Estudio de Asociación del Genoma Completo/normas , Técnicas de Genotipaje/normas , HumanosRESUMEN
In this paper, a biodegradable gold coated zein film surface enhanced Raman spectroscopy (SERS) platform, with gold nanoparticles (AuNPs) deposited on the surface to further enhance the Raman signal, was used to detect pyocyanin (PYO), the toxin secreted by Pseudomonas aeruginosa. An inverted pyramid structure imprinted on a zein film and gold coated during the transfer process was further improved with the deposition and fixing of gold nanoparticles, which resulted in enhancement of the SERS signal by approximately a decade. This new platform served as a lab-on-a-chip sensor to enable the sensitive and rapid detection of PYO in drinking water. The size, distribution, and morphology of the zein film nanostructures including the presence and distribution of gold nanoparticles were characterized by scanning electron microscopy (SEM). The new zein-based platform has the advantage of being largely biodegradable compared with commercial silicon- or glass-based platforms. The limit of detection for PYO using the newly developed zein-based SERS sensor platform was calculated as 25 µM, considerably lower than the concentration of PYO in the blood of people with cystic fibrosis which has been reported to be 70 µM.
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Toxinas Bacterianas/análisis , Técnicas Biosensibles/métodos , Piocianina/análisis , Espectrometría Raman/métodos , Contaminantes Químicos del Agua/análisis , Técnicas Biosensibles/instrumentación , Agua Potable/análisis , Oro/química , Límite de Detección , Nanopartículas del Metal/química , Espectrometría Raman/instrumentación , Zeína/químicaRESUMEN
Unique colorimetric optical properties of nanomaterials can effectively influence the light absorption or emission of molecules. Here, we design plasmonic substrate for surface-enhanced Raman scattering (SERS) by inducing three-dimensional (3D) hot spots on the sensing surface. The 3D hot spots are formed by the self-assembly of plasmonic nanoparticles (NPs) on a 3D plasmonic nanocup array structure. This 3D hot spot formation on the periodic nanocup arrays achieves much higher SERS enhancement factor than the 2D NP arrays, which have been conventionally sought SERS substrates. We also utilize the colorimetric properties of the nanocup arrays for an additional degree of SERS enhancement. Colorimetry, achieved by tunable plasmon resonance wavelength by controlling dielectric property on the nanocup array surface, eases the modulation of the plasmonic resonance condition without modifying the nanostructure design. By continuously monitoring the shifts of the plasmon resonance condition and its effect on the light absorption and emission of the nearby molecules, we verify that larger SERS enhancement is achieved when the plasmon resonance wavelength is matched with the Raman excitation wavelength. The ease of plasmon resonance tuning of this nanocup array-nanoparticle hybrid structure allows versatile SERS enhancement for a variety of different Raman measurement conditions.