Co-Immunization of Plasmid DNA Encoding IL-12 and IL-18 with Bacillus Calmette-Guérin Vaccine against Progressive Tuberculosis

∙ The authors have no financial conflicts of interest. Purpose: Bacillus Calmette-Guérin (BCG) vaccine has widely been used to immunize against tuberculosis, but its protective efficacy is variable in adult pulmonary tuberculosis, while it is not efficiently protective against progressive infection of virulent Mycobacterium tuberculosis strains. In this study, the protective effects of plasmid DNA vaccine constructs encoding IL-12 or IL-18 with the BCG vaccine were evaluated against progressive infection of M. tuberculosis, using mouse aerosol challenge model. Materials and Methods: Plasmid DNA vaccine constructs encoding IL-12 or IL-18 were constructed and mice were immunized with the BCG vaccine or with IL-12 DNA or IL-18 DNA vaccine constructs together with the BCG vaccine. Results: The BCG vaccine induced high level of interferon gamma (IFN-γ) but co-immunization of IL-12 or IL-18 DNA vaccine constructs with the BCG vaccine induced significantly higher level of IFN-γ than a single BCG vaccine. The BCG vaccine was highly protective at early stage of M. tuberculosi

Different degree of cytokinemia and T-cell activation according to serum IL-6 levels in critical COVID-19

IntroductionTocilizumab, a humanized anti-interleukin-6 receptor (IL-6R) antibody, is recommended for the treatment of severe to critical coronavirus diseases 2019 (COVID-19). However, there were conflicting results on the efficacy of tocilizumab. Therefore, we hypothesized that the differences in tocilizumab efficacy may stem from the different immune responses of critical COVID-19 patients. In this study, we described two groups of immunologically distinct COVID-19 patients, based on their IL-6 response.MethodsWe prospectively enrolled critical COVID-19 patients, requiring oxygen support with a high flow nasal cannula or a mechanical ventilator, and analyzed their serial samples. An enzyme-linked immunosorbent assay and flow cytometry were used to evaluate the cytokine kinetics and cellular immune responses, respectively.ResultsA total of nine patients with critical COVID-19 were included. The high (n = 5) and low IL-6 (n = 4) groups were distinguished by their peak serum IL-6 levels, using 400 pg/mL as the cut-off value. Although the difference of flow cytometric data did not reach the level of statistical significance, the levels of pro-inflammatory cytokines and the frequencies of intermediate monocytes (CD14+CD16+), IFN-γ+ CD4+ or CD8+ T cells, and HLA-DR+PD-1+ CD4+ T cells were higher in the high IL-6 group than in the low IL-6 group.ConclusionThere were distinctive two groups of critical COVID-19 according to serum IL-6 levels having different degrees of cytokinemia and T-cell responses. Our results indicate that the use of immune modulators should be more tailored in patients with critical COVID-19

Machine Learning-Based Analyses of the Effects of Various Types of Air Pollutants on Hospital Visits by Asthma Patients

Asthma is a chronic respiratory disorder defined by airway inflammation, chest pains, wheezing, coughing, and difficulty breathing that affects an estimated 300 million individuals globally. Although various studies have shown an association between air pollution and asthma, few studies have used statistical and machine learning algorithms to investigate the effect of each individual air pollutant on asthma. The purpose of this research was to assess the association between air pollutants and the frequency of hospital visits by asthma patients using three analysis methods: linear correlation analyses were performed by Pearson correlation coefficients, and least absolute shrinkage and selection operator (LASSO) and random forest (RF) models were used for machine learning-based analyses to investigate the effect of air pollutants. This research studied asthma patients using the hospital visit database in Seoul, South Korea, collected between 2013 and 2017. The data set included outpatient hospital visits (n = 17,787,982), hospital admissions (n = 215,696), and emergency department visits (n = 85,482). The daily atmospheric environmental information from 2013 to 2017 at 25 locations in Seoul was evaluated. The three analysis models revealed that NO2 was the most significant pollutant on average in outpatient hospital visits by asthma patients. For example, NO2 had the greatest impact on outpatient hospital visits, resulting in a positive association (r=0.331). In hospital admissions of asthma patients, CO was the most significant pollutant on average. It was observed that CO exhibited the most positive association with hospital admissions (I = 3.329). Additionally, a significant time lag was found between both NO2 and CO and outpatient hospital visits and hospital admissions of asthma patients in the linear correlation analysis. In particular, NO2 and CO were shown to increase hospital admissions at lag 4 in the linear correlation analysis. This study provides evidence that PM2.5, PM10, NO2, CO, SO2, and O3 are associated with the frequency of hospital visits by asthma patients

Relationship between dietary factors and bisphenol a exposure: the second Korean National Environmental Health Survey (KoNEHS 2012–2014)

Abstract Background This study was aimed at finding out the exposure level of bisphenol A (BPA), a well-known endocrine disruptor, in relation to dietary factors using a data representing the Korean general population. Methods This study was performed on 5402 adults aged 19 years and older based on the Second Korean National Environmental Health Survey (KoNEHS 2012–2014). The data analyzed urinary BPA concentration in relation to socio-demographic variables, health behavior-related variables, and dietary factor-related variables. Odds ratio (OR) was calculated through a logistic regression analysis after dividing the participants into high BPA exposure group and low BPA exposure group based on the top 75 percentile concentration. The logistic regression analysis was carried out considering the appropriate sample weight, stratification, and clustering of the second KoNEHS sample design. Results The group drinking bottled water at home and the group using zip-top bags/plastic bags showed significantly higher urinary BPA concentration in female. OR tends to increase as the intake frequency of frozen food increased and OR of frozen food consumption of more than once a week was 1.48 (95% confidence interval (CI) 1.02–2.24) for male and the group drinking bottled water showed significantly higher OR of 1.45 (95% CI 1.06–2.17) after adjusting the related factors for female. Conclusions BPA levels were high in female using bottled water and in male consuming frozen food, and therefore bottled water and frozen food need to be avoided to reduce BPA levels

Shaping Rollable Display Devices: Effects of Gripping Condition, Device Thickness, and Hand Length on Bimanual Perceived Grip Comfort

Objective: To examine the effects of the gripping condition, device thickness, and hand length on bimanual perceived grip comfort associated with unrolling hand-held rollable screens. Background: Rollable displays can be rolled and unrolled to change screen size. Although diverse rollable display device concepts have been suggested, little is known regarding ergonomic forms for comfortable screen unrolling. Method: Thirty young individuals (10 in each hand-length group) evaluated three rollable display device prototypes in three gripping conditions (no restriction on using side bezels, minimal use of side bezels, and restriction on the gripping type). Prototypes differed in their right-side thickness (2, 6, and 10 mm). Side bezel regions grasped during screen unrolling and corresponding bimanual grip comfort ratings were obtained. Results: To improve perceived grip comfort and accommodate user-preferred gripping methods, rollable display devices should be 6 mm (preferably 10 mm) thick (vs. 2 mm) and have at least 20-mm-wide side bezels. Relative to device thickness, gripping conditions were more influential on grip comfort ratings. The "no restriction" condition improved grip comfort ratings and strengthened bimanual coupling in terms of grip comfort ratings. Conclusion: Contrary to current smartphone trends toward thinner and bezel-less designs, hand-held rollable display devices should be sufficiently thick and have sufficiently wide side bezels for screen unrolling. Application: Hand-held rollable display devices should be 6- or preferably 10-mm thick (vs. 2 mm) and have at least 20-mm-wide side bezels to ensure higher perceived grip comfort during bilateral screen unrolling

MiR-9, miR-21, and miR-155 as potential biomarkers for HPV positive and negative cervical cancer

Abstract Background Cervical cancer is the second leading cause of death among female patients with cancer in the world. High risk human papillomavirus has causal roles in cervical cancer initiation and progression by deregulating several cellular processes. However, HPV infection is not sufficient for cervical carcinoma development. Therefore, other genetic and epigenetic factors may be involved in this complex disease, and the identification of which may lead to better diagnosis and treatment. Our aim was to analyze the expression of microRNAs in cervical cancer cases positive or negative for HPV E6/E7 mRNA, and to assess their diagnostic usefulness and relevance. Methods The expression of three different microRNAs (miR-9, miR-21, and miR-155) in 52 formalin-fixed paraffin-embedded (FFPE) primary cervical cancer tissue samples and 50 FFPE normal cervical tissue samples were evaluated. Results MiR-9, miR-21, and miR-155 were significantly overexpressed in cervical cancer tissues compared to normal tissues (P < 0.001). MiR-21 and miR-155 expression combined with the HPV E6/E7 mRNA assay in HPV E6/E7 negative cervical cancer showed increased AUC of 0.7267 and 0.7000, respectively (P = 0.01, P = 0.04), demonstrating their potential as diagnostic tools. Moreover, miR-21 and miR-155 were predictors showing a 7 fold and 10.3 fold higher risk for HPV E6/E7 negative patients with cervical cancer (P = 0.024 and P = 0.017, respectively) while miR-155 was a predictor showing a 27.9 fold higher risk for HPV E6/E7 positive patients with cervical cancer (P < 0.0001). Conclusions There is a strong demand for additional, alternative molecular biomarkers for diagnosis and management of precancer patients. MiR-21 and miR-155 may be helpful in the prediction of both HPV positive and HPV negative cases of cervical cancer