Constructing a Mixed Simulation With 360° Virtual Reality and a High-Fidelity Simulator: Usability and Feasibility Assessment.

Virtual reality technology has been adopted to overcome barriers of conventional simulation. This study was conducted to determine the impact of mixed simulation (a 360° virtual reality and a high-fidelity simulator) on learning how to provide nursing care for patients with arrhythmia. A total of 49 students were randomly assigned to intervention (n = 25) and control (n = 23) groups. They were given four arrhythmia cases with a 360° virtual reality system first followed by a manikin-based simulation. The mixed simulation group showed greater improvement in knowledge, higher decision-making competency in "knowing and acting" ( P = .025) and "seeking information from instructors" ( P = .049), and lower anxiety in "using resources to gather information" ( P = .031). Study participants achieved a good level of empathy (3.28 ± 0.72) and liked the program (4.56 ± 0.60). They were satisfied with the program (4.48 ± 0.65). These findings provide new insight into learning through blending of new technology. When the 360° virtual reality was used with existing manikin-based simulation, they effectively reinforced one another. The 360° virtual reality can be an effective strategy to ensure active participation to gain a comprehensive understanding of and empathy for patients.

Prenatal cocaine exposure and substance use disorder in emerging adulthood at age 21.

BACKGROUND: Prenatal cocaine exposure (PCE) has been associated with child and adolescent externalizing behaviors and early substance use, yet few studies investigated its association with substance use disorder (SUD) in emerging adults. The present study examined the association of PCE with SUD in emerging adulthood, and whether childhood externalizing behaviors and adolescent substance use mediated the relationship. METHODS: Participants were 367 (187 PCE; 53% female) adults at age 21, primarily urban African American who were recruited at birth. PCE and exposure to alcohol, tobacco, and marijuana were determined using biologic assays for drug metabolites and/or maternal self-report at birth. Offspring externalizing problems were assessed using the Youth Self-Report at age 12, substance use and substance use-related problems via biologic assays and/or self-report at age 15, and SUD determined using DSM-5 diagnostic criteria at age 21. RESULTS: About 32.3% of the emerging adults were determined to have marijuana use disorder, 30.3% tobacco use disorder, and 15.5% alcohol use disorder. PCE was related to greater externalizing behaviors at age 12 (ß = 0.12, p = .042), which in turn was related to SUD (ß = 0.22, p = .008). PCE was also related to substance use, mainly marijuana, at age 15 (ß = 0.22, p = .011), which was related to SUD (ß = 0.51, p < .001). Total indirect effects including these two pathways were significant (ß = 0.19, p = .002). CONCLUSIONS: PCE may increase risk for SUD in emerging adulthood through childhood externalizing behaviors and adolescent substance use.

Self-reported mental health outcomes in prenatally cocaine exposed adolescents at 17 years of age.

OBJECTIVE: Adverse developmental effects of prenatal cocaine exposure (PCE) are hypothesized to extend into late adolescence, yet few studies have investigated the association between PCE and late adolescent mental health outcomes. We examined the associations between PCE and self-reported mental health symptoms at age 17, controlling for biologic and environmental confounders. We further explored the potential moderating role of sex and the mediating role of earlier drug use by age 15 in the associations. METHOD: 327 (162 PCE; 165 non-cocaine exposed, NCE) urban adolescents, primarily African Americans, of low socioeconomic status, were prospectively recruited at birth for a longitudinal study and participated in the current study. We administered the Computerized Diagnostic Interview Schedule for Children-IV to assess their mental health symptoms at age 17. Alcohol, tobacco, and marijuana use by age 15 were assessed using biologic samples and self-reports. Confounders included other prenatal drug exposures, caregiving environment, and childhood maltreatment. RESULTS: Although no overall associations between PCE and mental health outcomes were observed, multivariate logistic regression models indicate girls with PCE were 3.60 times (95% CI = 1.45-8.96, p = .006) more likely to have symptoms of oppositional defiance disorder than girls with NCE. This relationship was partially mediated by marijuana use by age 15. CONCLUSION: Continued studies into emerging adulthood will further elucidate the long-term mental health outcomes associated with PCE.

Evaluation of In-Hospital Cluster of COVID-19 Associated With a Patient With Prolonged Viral Shedding Using Whole-Genome Sequencing.

BACKGROUND: Patients with hematologic malignancies may produce replication-competent virus beyond 20 days of SARS-CoV-2 infection. However, data regarding the transmission of SARS-CoV-2 from patients with prolonged viral shedding is limited. METHODS: In May 2022, four additional cases of COVID-19 were reported in a hematologic ward at a tertiary care hospital in South Korea, after an 8-week isolation of a patient with prolonged viral shedding. We performed whole-genome sequencing (WGS) of SARS-CoV-2 to evaluate the possibility of post-isolation transmission from this prolonged viral shedding. RESULTS: A patient (case 1) with acute myeloid leukemia was released from isolation 54 days after the diagnosis of COVID-19 based on rising Ct value of up to 29.3, and moved to a six-patient room. On days 10 and 11 post-isolation, his doctor (case 2) and 2 patients who were his roommates (case 3, 4) had positive SARS-CoV-2 PCR results. Additionally, 16 days post-isolation, another patient (case 5) in a remote room had positive SARS-CoV-2 PCR result. All the three patients were hospitalized for ≥ 14 days when they were diagnosed with SARS-CoV-2 infection. Except for case 3, the remaining 4 cases were available for WGS, which revealed that case 1 exhibited a 7 nucleotides difference in comparison to cases 4 and 5 and case 2 displayed a 20 nucleotides difference compared with case 1, while sequences of cases 4 and 5 were identical. CONCLUSIONS: Despite the possibility of transmission from the patient with prolonged viral shedding, no evidence of the transmission of SARS-CoV-2 from the patient with prolonged positive RT-PCR using WGS was found.

Substance use and individual assets in urban adolescents: Subgroups and correlates in emerging adulthood.

INTRODUCTION: To investigate patterns of divergence in adolescent adjustment, this study examined the co-occurring patterns of adolescents' individual assets (e.g., school engagement, values) and substance use, and whether the co-occurring patterns were associated with later functioning in emerging adulthood. METHODS: Participants were 358 (54% females), predominantly African American, urban adolescents, recruited at birth for a prospective study on the effects of prenatal substance exposure in the Midwest United States. Individual assets, using the Developmental Assets Profile, substance use (alcohol, tobacco, marijuana), via biologic assays and self-report, and substance use-related problems were assessed at age 15 years. High-school completion, substance use disorder, mental health symptoms, and legal problems were assessed at age 21 years. RESULTS: Latent class analysis identified five classes as follows: high assets with low substance use (C1, 10.2%); moderate assets with low substance use (C2, 28.7%); low assets with low substance use (C3, 32%); moderate assets with high substance use (C4, 9.4%); and low assets with high substance use (C5, 19.2%). Despite similar levels of assets, adolescents in C5 reported more life adversities (suboptimal caregiving environment, daily hassles, non-birth parents' care) than those in C3. C4 and C5 reported more substance use disorder at age 21 years than the three low substance use classes; adolescents in C5 were less likely to complete high school than those in C2. More females in C5 reported greater mental health symptoms than those in C1 and C3, and criminal justice involvement than those in C1. CONCLUSIONS: The current findings underscore the significance of substance use in adolescence in disrupting healthy transition to adulthood, especially among females in the context of low individual assets.

Adverse Reactions Following the First Dose of ChAdOx1 nCoV-19 Vaccine and BNT162b2 Vaccine for Healthcare Workers in South Korea.

BACKGROUND: We performed a prospective survey on the adverse reactions following the first dose of two types of vaccines against coronavirus disease 2019 (COVID-19) in healthcare workers (HCWs) in South Korea. METHODS: HCWs at a tertiary referral hospital in Seoul, South Korea, received a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) or an mRNA-based vaccine (BNT162b2) between March 5 and March 26, 2021. The HCWs were asked to report adverse reactions through a mobile self-report questionnaire for three days after vaccination. RESULTS: A total of 7,625 HCWs received the first dose of ChAdOx1 or BNT162b2 vaccine during the study period. Of them, 5,866 (76.9%) HCWs (ChAdOx1, n = 5,589 [95.3%]; BNT162b2, n = 277 [4.7%]) participated at least once in the survey, of whom 77% were female and 86% were younger than 50 years. The overall adverse reaction rate was 93% in the ChAdOx1 group and 80% in the BNT162b2 group (P < 0.001). Both local and systemic reactions were more commonly reported in the ChAdOx1 group, and the difference was larger in systemic reactions such as fever and fatigue. In the ChAdOx1 group, the incidence of adverse reactions was significantly higher in females and those in the younger age groups, while the BNT162b2 group showed such difference according to age. CONCLUSION: In our prospective survey, vaccine-associated adverse reactions were more commonly reported in the ChAdOx1 group than in the BNT162b2 group. Females and younger age groups experienced vaccine-associated adverse reactions more frequently.

Identification of drug combinations on the basis of machine learning to maximize anti-aging effects.

Aging is a multifactorial process that involves numerous genetic changes, so identifying anti-aging agents is quite challenging. Age-associated genetic factors must be better understood to search appropriately for anti-aging agents. We utilized an aging-related gene expression pattern-trained machine learning system that can implement reversible changes in aging by linking combinatory drugs. In silico gene expression pattern-based drug repositioning strategies, such as connectivity map, have been developed as a method for unique drug discovery. However, these strategies have limitations such as lists that differ for input and drug-inducing genes or constraints to compare experimental cell lines to target diseases. To address this issue and improve the prediction success rate, we modified the original version of expression profiles with a stepwise-filtered method. We utilized a machine learning system called deep-neural network (DNN). Here we report that combinational drug pairs using differential expressed genes (DEG) had a more enhanced anti-aging effect compared with single independent treatments on leukemia cells. This study shows potential drug combinations to retard the effects of aging with higher efficacy using innovative machine learning techniques.

Universal Screening of Severe Acute Respiratory Syndrome Coronavirus 2 with Polymerase Chain Reaction Testing after Rally of Trainee Doctors.

There were two rallies of medical students and trainee doctors, where 9,000 participants gathered. We performed polymerase chain reaction (PCR)-based universal screening for the participants using pooling at a tertiary care hospital. Around 609 (94%) of 646 participants underwent PCR tests for severe acute respiratory syndrome coronavirus 2; all of them tested negative. Our data suggested low transmission rates in open air mass gatherings when appropriate personal protective practices were followed.

Tuning of polarized room-temperature thermal radiation based on nanogap plasmon resonance.

When a one-dimensional (1D) metal array is coupled to a planar metal mirror with a dielectric gap, localized plasmon resonance is excited inside the gap at a specific polarization of light in free space. Herein, we report on the completely polarized, mid-infrared thermal radiation that is released from gap plasmon resonators with a nanometer-thick dielectric. We fabricated nanogap plasmon resonators with 1D Au or Ni array of various widths (w) using laser interference lithography. An atomic layer deposition process was used to introduce a 10 nm-thick alumina gap between a 1D metal array and a planar metal mirror. It was observed that only for the Au nanogap plasmon resonators, high-amplitude absorption peaks that were attributed to gap plasmon modes with different orders appeared at discrete wavelengths in a polarization-resolved spectrum. In addition, all the pronounced peaks were gradually redshifted with increasing w. At w = 1.2-1.6 µm, the fundamental gap plasmon mode was tuned to the main wavelengths (8-9 µm) of thermal radiation at room temperature (e.g., ∼300 K), which led to polarization-selective camouflage against standard infrared thermal imaging. The results of electromagnetic simulations quantitatively agreed with the measured absorbance spectra in both peak wavelength and amplitude. We believe that these experimental efforts towards achieving radiation/absorption spectra tailored at mid-infrared wavelengths will be further exploited in thermal-radiation harnessed energy devices, spectroscopic sensors, and radiative coolers.

Gamma-irradiation-killed Streptococcus pneumoniae potently induces the expression of IL-6 and IL-8 in human bronchial epithelial cells.

Streptococcus pneumoniae is a major respiratory pathogen that can cause pneumonia, meningitis, and otitis media. Although capsular polysaccharide-based vaccines are commercially available, there is a need for broad-spectrum, serotype-independent, and cost-effective vaccines. Recently, an intranasal vaccine formulated with gamma-irradiated nonencapsulated S. pneumoniae whole cells has been developed and its immunogenicity is under investigation. Since innate immunity influences the subsequent adaptive immunity, in the present study, we investigated the immunostimulatory activity of gamma-irradiated S. pneumoniae (r-SP) in the human bronchial epithelial cell-line, BEAS-2B, by comparing with heat-inactivated S. pneumoniae (h-SP) and formalin-inactivated S. pneumoniae (f-SP). r-SP potently induced interleukin (IL)-6 and IL-8 at both mRNA and protein levels in a dose- and time-dependent manner, whereas h-SP and f-SP poorly induced them. Of note, the mRNA levels of IL-6 and IL-8 were approximately two-fold higher when cells were stimulated with 3 × 107 CFU/ml of r-SP for 3 h, while the protein levels of IL-6 and IL-8 were approximately five-fold higher after stimulation with 3 × 107 CFU/ml of r-SP for 24 h. Furthermore, r-SP exhibited potent activation of Toll-like receptor 2 compared with h-SP or f-SP. The expression of IL-6 and IL-8 induced by r-SP was mediated through the activation of mitogen-activated protein kinases. Remarkably, when r-SP was further treated with heat or formalin, there was a decrease in the aforementioned activities. Taken together, we suggest that r-SP stimulates the human respiratory epithelial cells to produce the cytokines IL-6 and IL-8, which might influence the induction of adaptive immune responses.

Th17 activation by dendritic cells stimulated with gamma-irradiated Streptococcus pneumoniae.

Dendritic cells (DCs) play an important role in antigen presentation, which is an essential step for the induction of antigen-specific adaptive immunity. Inactivated bacterial whole cell vaccines have been widely used to prevent many bacterial infections because they elicit good immunogenicity due to the presence of various antigens and are relatively inexpensive and easy to manufacture. Recently, gamma-irradiated whole cells of nonencapsulated Streptococcus pneumoniae were developed as a broad-spectrum and serotype-independent multivalent vaccine. In the present study, we generated gamma-irradiated S. pneumoniae (r-SP) and investigated its capacity to stimulate mouse bone marrow-derived DCs (BM-DCs) in comparison with heat-inactivated and formalin-inactivated S. pneumoniae (h-SP and f-SP, respectively). r-SP showed an attenuated binding and internalization level to BM-DCs when compared to h-SP or f-SP. r-SP weakly induced the expression of CD80, CD83, CD86, MHC class I, and PD-L2 compared with h-SP or f-SP. Furthermore, r-SP less potently induced IL-6, TNF-α, and IL-23 expression than h-SP or f-SP but more potently induced IL-1ß expression than h-SP or f-SP in BM-DCs. Since Th17-mediated immune responses are known to be important for the protection against pneumococcal infections, r-SP-primed DCs were co-cultured with splenocytes or splenic CD4+ T cells. Interestingly, r-SP-sensitized BM-DCs markedly induced IL-17A+ CD4+ T cells whereas h-SP- or f-SP-sensitized BM-DCs weakly induced them. Collectively, these results suggest that r-SP could be an effective pneumococcal vaccine candidate eliciting Th17-mediated immune responses by stimulation of DCs.

Gamma-irradiation of Streptococcus pneumoniae for the use as an immunogenic whole cell vaccine.

Streptococcus pneumoniae is a major respiratory pathogen that causes millions of deaths worldwide. Although subunit vaccines formulated with the capsular polysaccharides or their protein conjugates are currently-available, low-cost vaccines with wide serotype coverage still remain to be developed, especially for developing countries. Recently, gamma- irradiation has been considered as an effective inactivation method to prepare S. pneumoniae vaccine candidate. In this study, we investigated the immunogenicity and protective immunity of gamma-irradiated S. pneumoniae (r-SP), by comparing with heat-inactivated S. pneumoniae (h-SP) and formalin-inactivated S. pneumoniae (f-SP), both of which were made by traditional inactivation methods. Intranasal immunization of C57BL/6 mice with r-SP in combination with cholera toxin as an adjuvant enhanced S. pneumoniaespecific antibodies on the airway mucosal surface and in sera more potently than that with h-SP or f-SP under the same conditions. In addition, sera from mice immunized with r-SP potently induced opsonophagocytic killing activity more effectively than those of h-SP or f-SP, implying that r-SP could induce protective antibodies. Above all, immunization with r-SP effectively protected mice against S. pneumoniae infection. Collectively, these results suggest that gamma- irradiation is an effective method for the development of a killed whole cell pneumococcal vaccine that elicits robust mucosal and systemic immune responses.

Correction: A novel highly potent trivalent TGF-ß receptor trap inhibits early-stage tumorigenesis and tumor cell invasion in murine Pten-deficient prostate glands.

[This corrects the article DOI: 10.18632/oncotarget.13343.].

Types of household humidifier disinfectant and associated risk of lung injury (HDLI) in South Korea.

From 2002 through 2015, hundreds of people died of fatal lung injuries associated with the use of humidifier disinfectants (HDs) in Korea. Several chemical disinfectants used for household humidifiers were later clinically confirmed to cause HD-associated lung injury (HDLI). The aim of this study is to evaluate the registered lung disease cases and to compare the distribution of HDLI patients, including deaths, by HD use characteristics including types of HD and HD brands categorized by age group. A total of 530 registered were clinically examined through two rounds of investigations conducted from July 2013 until April 2015. Information on HD use was obtained from a structured questionnaire and home investigations. Approximately one-half of the patients (n=221) were clinically confirmed to be associated with the use of HDs. Pregnant women (n=35, 16%) and pre-school children≤6years old (n=128, 58%) accounted for most of the HD-associated lung injury patients (n=163, 74%). Sixty-seven percent of HDLI patients developed HDLI after less than one year of HD use. HD products containing polyhexamethylene guanidine phosphate (PHMG) were the most frequently used among confirmed HDLI patients (n=123, 55.7%), followed by oligo (2-(2-ethoxy) ethoxyethyl guanidinium (PGH) (n=24, 10.9%) and a mixture of chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) (n=3, 1.4%). Other HDs did not appear to be linked to HDLI. The majority of the HDLI patients (n=85, 38.5%) was found to use only Oxy Saksak® products containing PHMG. The development of HDLI was clinically found to be associated with the use of several HD products containing PHMG and PGH, and to lesser extent, CMIT/MIT.

An engineered transforming growth factor ß (TGF-ß) monomer that functions as a dominant negative to block TGF-ß signaling.

The transforming growth factor ß isoforms, TGF-ß1, -ß2, and -ß3, are small secreted homodimeric signaling proteins with essential roles in regulating the adaptive immune system and maintaining the extracellular matrix. However, dysregulation of the TGF-ß pathway is responsible for promoting the progression of several human diseases, including cancer and fibrosis. Despite the known importance of TGF-ßs in promoting disease progression, no inhibitors have been approved for use in humans. Herein, we describe an engineered TGF-ß monomer, lacking the heel helix, a structural motif essential for binding the TGF-ß type I receptor (TßRI) but dispensable for binding the other receptor required for TGF-ß signaling, the TGF-ß type II receptor (TßRII), as an alternative therapeutic modality for blocking TGF-ß signaling in humans. As shown through binding studies and crystallography, the engineered monomer retained the same overall structure of native TGF-ß monomers and bound TßRII in an identical manner. Cell-based luciferase assays showed that the engineered monomer functioned as a dominant negative to inhibit TGF-ß signaling with a Ki of 20-70 nm Investigation of the mechanism showed that the high affinity of the engineered monomer for TßRII, coupled with its reduced ability to non-covalently dimerize and its inability to bind and recruit TßRI, enabled it to bind endogenous TßRII but prevented it from binding and recruiting TßRI to form a signaling complex. Such engineered monomers provide a new avenue to probe and manipulate TGF-ß signaling and may inform similar modifications of other TGF-ß family members.

A novel highly potent trivalent TGF-ß receptor trap inhibits early-stage tumorigenesis and tumor cell invasion in murine Pten-deficient prostate glands.

The effects of transforming growth factor beta (TGF-ß) signaling on prostate tumorigenesis has been shown to be strongly dependent on the stage of development, with TGF-ß functioning as a tumor suppressor in early stages of disease and as a promoter in later stages. To study in further detail the paradoxical tumor-suppressive and tumor-promoting roles of the TGF-ß pathway, we investigated the effect of systemic treatment with a TGF-ß inhibitor on early stages of prostate tumorigenesis. To ensure effective inhibition, we developed and employed a novel trivalent TGF-ß receptor trap, RER, comprised of domains derived from the TGF-ß type II and type III receptors. This trap was shown to completely block TßRII binding, to antagonize TGF-ß1 and TGF-ß3 signaling in cultured epithelial cells at low picomolar concentrations, and it showed equal or better anti-TGF-ß activities than a pan TGF-ß neutralizing antibody and a TGF-ß receptor I kinase inhibitor in various prostate cancer cell lines. Systemic administration of RER inhibited prostate tumor cell proliferation as indicated by reduced Ki67 positive cells and invasion potential of tumor cells in high grade prostatic intraepithelial neoplasia (PIN) lesions in the prostate glands of Pten conditional null mice. These results provide evidence that TGF-ß acts as a promoter rather than a suppressor in the relatively early stages of this spontaneous prostate tumorigenesis model. Thus, inhibition of TGF-ß signaling in early stages of prostate cancer may be a novel therapeutic strategy to inhibit the progression as well as the metastatic potential in patients with prostate cancer.

A cadaveric study on mylohyoid herniation of the sublingual gland.

The purpose of this study was to document the presence of a sublingual gland (SLG) herniating inferiorly through the mylohyoid muscle into the submandibular area. A total of 100 half-heads of 50 adult Korean cadavers were enrolled in this study. The floor of the mouth was dissected from the neck, and mylohyoid muscle patency and position of the sublingual gland were evaluated. Demographic factors of the donor and characteristics of the herniation were evaluated. Herniation was found in 29 (58.0 %) of the 50 cadavers or 42 of the 100 half-heads. Herniation was more frequently observed in females than in males (p = 0.009). However, no laterality was observed. Classifying the location of SLG herniation from the midpoint of the mandible to the hyoid bone into 3 regions, 32 (63 %) of herniations were found in the anterior one-third. No ranula formation was observed. The size and weight of normal glands tended to be larger than those of herniated glands, but no statistical significance was observed. An SLG hernia is a very common condition and is more frequently observed in females. As such, SLG herniation should be considered when a submental neck mass is evaluated.

Identification and characterization of NF1 splicing mutations in Korean patients with neurofibromatosis type 1.

Neurofibromatosis type I (NF1) is an autosomal dominant genetic disorder caused by NF1 mutations. Although mutations affecting mRNA splicing are the most common molecular defects in NF1, few studies have analyzed genomic DNA (gDNA)-mRNA correlations in Korean NF1 patients. In this study, we investigated 28 unrelated NF1 patients who showed splicing alterations in reverse transcription-PCR of NF1 mRNA and identified 24 different NF1 splicing mutations, 9 of which were novel. These mutations can be categorized into five groups: exon skipping resulting from mutations at authentic 5' and 3' splice sites (type I, 46%), cryptic exon inclusion caused by deep intronic mutations (type II, 8%), creation of new splice sites causing loss of exonic sequences (type III, 8%), activation of cryptic splice sites due to disruption of authentic splice sites (type IV, 25%) and exonic sequence alterations causing exon skipping (type V, 13%). In total, 42% of all splicing mutations did not involve the conserved AG/GT dinucleotides of the splice sites, making it difficult to identify the correct mutation sites at the gDNA level. These results add to the mutational spectrum of NF1 and further elucidate the gDNA-mRNA correlations of NF1 mutations.

Dendritic Cells Differentiated from Human Umbilical Cord Blood-Derived Monocytes Exhibit Tolerogenic Characteristics.

Human umbilical cord blood (UCB) is rich in diverse hematopoietic stem cells that are competent to differentiate into various cell types with immunological compatibility at transplantation. Thus, UCB is a potential source for the preparation of dendritic cells (DCs) to be used for cell therapy against inflammatory disorders or cancers. However, the immunological properties of UCB-derived DCs are not fully characterized. In this study, we investigated the phenotypes and functions of UCB monocyte-derived DCs (UCB-DCs) in comparison with those of adult peripheral blood (APB) monocyte-derived DCs (APB-DCs). UCB-DCs contained less CD1a(+) DCs, which is known as immunostimulatory DCs, than APB-DCs. UCB-DCs exhibited lower expression of CD80, MHC proteins, and DC-SIGN, but higher endocytic activity, than APB-DCs. Lipopolysaccharide stimulation of UCB-DCs minimally augmented the expression of maturation markers and production of interleukin (IL)-12 and tumor necrosis factor (TNF)-α, but potently expressed IL-10. When UCB-DCs were cocultured with CD14(+) cell-depleted allogeneic peripheral blood mononuclear cells, they weakly induced the proliferation, surface expression of activation markers, and interferon (IFN)-γ production of T lymphocytes compared with APB-DCs. UCB possessed higher levels of prostaglandin E2 (PGE2) than APB, which might be responsible for tolerogenic phenotypes and functions of UCB-DCs. Indeed, APB-DCs prepared in the presence of PGE2 exhibited CD1a(-)CD14(+) phenotypes with tolerogenic properties, including weak maturation, impaired IL-12 production, and negligible T lymphocyte activation as UCB-DCs did. Taken together, we suggest that UCB-DCs have tolerogenic properties, which might be due to PGE2 highly sustained in UCB.

Relationship between Exposure to Household Humidifier Disinfectants and Risk of Lung Injury: A Family-Based Study.

BACKGROUND: In South Korea, a cluster of acute lung disease patients included lung injury disease suspected of being caused by the use of humidifier disinfectants. We examined the relationship between humidifier disinfectant exposure and clinically diagnosed humidifier disinfectant-associated lung injury (HDLI) in a family-based study. METHODS: This case-control study included 169 clinically confirmed HDLI cases and 303 family controls who lived with the HDLI patients. A range of information on exposure to humidifier disinfectants was obtained using a structured questionnaire and field investigations. Odds ratios (ORs) and confidence intervals (CIs) were estimated using unconditional logistic regression models that were adjusted for age, sex, presence of a factory within 1 km of residence, and the number of household chemical products used. RESULTS: HDLI risk increased approximately two-fold or more among the highest quartile compared with the lowest quartile in terms of the hours sleeping in a room with an operating humidifier treated with disinfectant (adjusted OR = 2.0, 95 % CI = 1.1-3.7), average hours of disinfectant-treated humidifier use per day (adjusted OR = 2.1, 95 % CI = 1.0-4.5), airborne disinfectant intensity (adjusted OR = 2.6, 95% CI = 1.2-5.3), and cumulative disinfectant inhalation level (adjusted OR = 2.0, 95% CI = 1.0-4.1). HDLI risk increased as the distance of the bed from humidifier gets shorter; compared with longer distance (> 1 m), the odds ratio was 2.7 for 0.5 to 1 m (95 % CI = 1.5-5.1) and 13.2 for <0.5 m (95 % CI = 2.4-73.0). CONCLUSIONS: The use of household humidifier disinfectants was associated with HDLI risk in a dose-response manner.