Influencing Factors of Delayed Diagnosis of COVID-19 in Gangwon, South Korea.

This study aimed to identify the time to diagnosis among COVID-19 patients and factors associated with delayed diagnosis (DD). Data from COVID-19 patients in Gangwon, South Korea, diagnosed between 22 February 2020 and 29 January 2022, were analyzed, excluding asymptomatic cases and those who underwent mandatory testing. DD was defined as a period exceeding 2 or more days from symptom recognition to COVID-19 diagnosis. Univariate analysis was performed to investigate the demographic characteristics, COVID-19 symptoms, and underlying medical conditions associated with DD, followed by multivariate logistic regression analysis for significant variables. Among 2683 patients, 584 (21.8%) were diagnosed within a day of symptom onset. DD rates were lower in patients with febrile symptoms but higher among those with cough, myalgia, or anosmia/ageusia. High-risk underlying medical conditions were not significantly associated with DD. Older age groups, the Wonju medical service area, time of diagnosis between November 2020 and July 2021, symptom onset on nonworkdays, and individuals in nonwhite collar sectors were significantly associated with increased DD risks. These findings were consistent in the sensitivity analysis. This study underscores the need for enhanced promotion and system adjustments to ensure prompt testing upon symptom recognition.

Exosome-Based Delivery of Super-Repressor IκBα Alleviates Alcohol-Associated Liver Injury in Mice.

Activation of Kupffer cells (KCs) by gut-derived lipopolysaccharide (LPS) instigates nuclear factor-κB (NF-κB)-mediated inflammatory responses in alcohol-associated liver diseases (ALD). Here, we utilized a novel optogenetically engineered exosome technology called 'exosomes for protein loading via optically reversible protein-protein interactions (EXPLOR)' to efficiently deliver the super-repressor IκB-loaded exosomes (Exo-srIκB) to the liver and examined its therapeutic potential in acute-on-chronic alcohol-associated liver injury. We detected enhanced uptake of DiI-labeled Exo-srIκB by LPS-treated inflammatory KCs, which suppressed LPS-induced inflammatory gene expression levels. In animal experiments, a single intravenous injection of Exo-srIκB prior to alcohol binge drinking significantly attenuated alcohol-associated hepatic steatosis and infiltration of neutrophils and macrophages but not a liver injury. Notably, three consecutive days of Exo-srIκB injection remarkably reduced alcohol-associated liver injury, steatosis, apoptosis of hepatocytes, fibrosis-related gene expression levels in hepatic stellate cells, infiltration of neutrophils and macrophages, and inflammatory gene expression levels in hepatocytes and KCs. In particular, the above effects occurred with inhibition of nuclear translocation of NF-κB in liver tissues, and these beneficial effects of Exo-srIκB on ALD were shown regardless of doses. Our results suggest an exosome-based modulation of NF-κB activity in KCs by Exo-srIκB as a novel and efficient therapeutic approach in ALD.

Child and adolescent health in Europe: Towards meeting the 2030 agenda.

Background: Childhood and adolescence are critical stages for a healthy life. To support countries in promoting health and development and improving health care for this age group, the WHO Regional Office for Europe developed the European strategy for child and adolescent health 2015-2020, which was adopted by all countries. This paper reports progress in the strategy's implementation until 2020. Methods: A survey was sent to all ministries of health of the 53 Member States of the WHO European Region. Responses were received from 45 Member States. Results are presented in this paper. Results: The European Region made overall progress in recent years, but increasing levels of overweight and obesity among children, adolescent mental health and low breastfeeding rates are recognized as key national challenges. Although forty-one countries adopted a national child and adolescent health strategy, only eight countries involve children in their review, development and implementation stages. Two-thirds of countries have a strategy for health-promoting schools and a school curriculum for health education. One-third of countries do not have legislation against marketing of unhealthy foods and beverages to children. Most countries reported routine assessment for developmental difficulties in children, but less than a quarter collected and reported data on children who are developmentally on track. There are major gaps in data collection for migrant children. Hospitalization rates for young children vary five-fold across the region, indicating over-hospitalization and access problems in some countries. Only ten countries allow minors access to health care without parental consent based on their maturity and only eleven countries allow school nurses to dispense contraceptives to adolescents without a doctor's prescription. Conclusions: This paper shows the progress in child and adolescent health made by countries in Europe until 2020 and key areas where additional work is needed to move the 2030 agenda forward. The survey was undertaken before the COVID-19 pandemic and the war in Ukraine. Both will likely exacerbate many of the observed problems and potentially reverse some gains reported. A renewed commitment is needed.

Technique for analyzing the transfer of colored cosmetics onto face masks.

BACKGROUND: With the rapid spread of COVID-19, the makeup trend in the cosmetics market is changing as mask-wearing has become a common practice. This study was conducted to establish an objective and reliable method for analyzing the transfer of colored cosmetics onto face masks. METHODS: A total of 24 women participated in this test. The participants were requested to wear Korean Filter 94 masks after having applied colored cosmetics on their faces and lips. VISIA-CR was used to photograph the face, and a camera was used to photograph the mask, which had smeared the cosmetics. Each image was analyzed using the Image-pro® 10 image analysis software. RESULTS: Immediately after applying the cosmetics, the intensity of the face decreased and the redness of the lips increased when compared with the results 30 minutes after washing the face. After wearing a mask, the intensity increased and the redness decreased when compared with immediately after applying the cosmetics. The area before and after the colored cosmetics smeared onto the mask was increased. CONCLUSION: It is expected that this study could be used as a reference for further experiments on analysis of methods for preventing mask stains.

Changes in skin wrinkles and pores due to long-term mask wear.

BACKGROUND: The spread of COVID-19 has made mask wear essential. Expecting that long-term mask wear would change the characteristics of skin, this study investigated changes in skin wrinkles and pores caused by long-term mask wear and whether or not use of moisturizers has an effect on any changes. MATERIALS AND METHODS: The study participants were 20 women who were instructed to wear a mask for at least 6 hours a day for 4 weeks. Measurements of skin wrinkles and pores were obtained before and after the 4 weeks of mask wear. The effects of application of a moisturizer were assessed by applying moisturizer within the mask-wearing area. They completed a questionnaire about skin changes at the end of the study period. RESULTS: After wearing the mask for 4 weeks, there was a significant increase in the skin wrinkles and pores; both variables decreased significantly in skin areas where a moisturizer had been applied. The results of the questionnaire-based survey indicated the study participants considered that long-term wearing of a mask had affected their skin. CONCLUSION: Wearing a mask for extended periods increases skin wrinkles and pores and using a moisturizer when wearing the mask helps to reduce this problem.

Effect of COVID-19 Non-Pharmaceutical Interventions and the Implications for Human Rights.

In response to the COVID-19 pandemic, many governments swiftly decided to order nationwide lockdowns based on limited evidence that such extreme measures were effective in containing the epidemic. A growing concern is that governments were given little time to adopt effective and proportional interventions protecting citizens' lives while observing their freedom and rights. This paper examines the effectiveness of non-pharmaceutical interventions (NPIs) in containing COVID-19, by conducting a linear regression over 108 countries, and the implication for human rights. The regression results are supported by evidence that shows the change in 10 selected countries' responding strategies and their effects as the confirmed cases increase. We found that school closures are effective in containing COVID-19 only when they are implemented along with complete contact tracing. Our findings imply that to contain COVID-19 effectively and minimize the risk of human rights abuses, governments should consider implementing prudently designed full contact tracing and school closure policies, among others. Minimizing the risk of human rights abuses should be a principle even when full contact tracing is implemented.

IgG and IgM responses to human papillomavirus L1 virus-like particle as a function of dosing schedule and vaccine formulation.

Most commercialized virus-like particle (VLP) vaccines use aluminum salt as adjuvant, even though VLPs provoke adequate antibody responses without adjuvant. We do not have detailed knowledge of how adjuvant affects the profile of anti-VLP antibodies. Meanwhile, there is evidence that differences between vaccination protocols influence the glycosylation of antibodies, which may alter their effector functions. In the present study a murine model was used to investigate the effects of dosing schedule and adjuvant on the antibody profiles and glycosylation levels of antigen-specific antibody responses to human papillomavirus type 16 L1 (HPV16 L1) VLPs. Mice received subcutaneously 2,000 ng of antigen divided into 4 or 7 doses. The HPV16 L1 VLPs elicited > 4 log10 anti-HPV16 L1 IgG titers without adjuvant, and aluminum hydroxide as adjuvant increased IgG titers 1.3- to 4-fold and reduced the anti-HPV16 L1 IgG2a / anti-HPV16 L1 IgG1 ratio value (use of aluminum hydroxide reduced the ratio of the IgG2a). Immunization with HPV16 L1 VLPs in combination with Freund's adjuvant enhanced IgG titers 5- to 12-fold. Seven-dose immunization markedly increased anti-HPV16 L1 IgM titers compared to four-dose immunization, as well as increasing the proportion of glycosylated antibodies. Our results suggest that antibody glycosylation can be controlled immunologically, and IgG and IgM profiles and glycosylation profiles of the vaccine-induced antibodies can be used as indicators reflecting the vaccine characteristics. These results indicate that the HPV16 L1 VLP dosing schedule can affect the quality of antigen-specific antibody responses. We suggest that dosing schedules should be noted in vaccination protocols for VLP-based vaccines.

Comparison of the size distributions and immunogenicity of human papillomavirus type 16 L1 virus-like particles produced in insect and yeast cells.

Insect and yeast cells are considered the expression systems of choice for producing virus-like particles (VLPs), and numerous types of VLPs have been produced in these systems. However, previous studies were restricted to identifying the characteristics of individual VLP preparations. No direct comparison of the structures and immunogenic properties of insect and yeast-derived VLPs has so far been made. In the present study, the size distribution and immunogenic properties of human papillomavirus type 16 (HPV16) L1 VLPs produced in Spodoptera frugipedra-9 insect cells and Saccharomyces cerevisiae were compared. The insect cell-derived VLPs were larger than the yeast ones (P < 0.0001), with median sizes of 34 and 26 nm, respectively. In addition, the insect-derived VLPs appeared to be more diverse in size than the yeast-derived VLPs. Immunization of mice with 30 ng per dose of VLPs elicited 2.7- and 2.4-fold higher anti-HPV16 L1 IgG and anti-HPV16 neutralizing antibody titers than immunization with the same amounts of the yeast-derived VLPs after the 4th immunizations, respectively. Our results suggest that the choice of expression system critically affects the particle size and immunogenic property of HPV16 L1 VLPs.

Kuwanon V inhibits proliferation, promotes cell survival and increases neurogenesis of neural stem cells.

Neural stem cells (NSCs) have the ability to proliferate and differentiate into neurons and glia. Regulation of NSC fate by small molecules is important for the generation of a certain type of cell. The identification of small molecules that can induce new neurons from NSCs could facilitate regenerative medicine and drug development for neurodegenerative diseases. In this study, we screened natural compounds to identify molecules that are effective on NSC cell fate determination. We found that Kuwanon V (KWV), which was isolated from the mulberry tree (Morus bombycis) root, increased neurogenesis in rat NSCs. In addition, during NSC differentiation, KWV increased cell survival and inhibited cell proliferation as shown by 5-bromo-2-deoxyuridine pulse experiments, Ki67 immunostaining and neurosphere forming assays. Interestingly, KWV enhanced neuronal differentiation and decreased NSC proliferation even in the presence of mitogens such as epidermal growth factor and fibroblast growth factor 2. KWV treatment of NSCs reduced the phosphorylation of extracellular signal-regulated kinase 1/2, increased mRNA expression levels of the cyclin-dependent kinase inhibitor p21, down-regulated Notch/Hairy expression levels and up-regulated microRNA miR-9, miR-29a and miR-181a. Taken together, our data suggest that KWV modulates NSC fate to induce neurogenesis, and it may be considered as a new drug candidate that can regenerate or protect neurons in neurodegenerative diseases.

Aminopropyl carbazole analogues as potent enhancers of neurogenesis.

Neural stem cells are multipotent and self-renewing cells that can differentiate into new neurons and hold great promise for treating various neurological disorders including multiple sclerosis, Parkinson's disease, and Alzheimer's disease. Small molecules that can trigger neurogenesis and neuroprotection are particularly useful not only because of their therapeutic implications but also because they can provide an invaluable tool to study the mechanisms of neurogenesis. In this report, we have developed and screened 25 aminopropyl carbazole derivatives that can enhance neurogenesis of cultured neural stem cells. Among these analogues, compound 9 demonstrated an excellent proneurogenic and neuroprotective activity with no apparent toxicity. We believe that compound 9 can serve as an excellent lead to develop various analogues and to study the underlying mechanisms of neurogenesis.

Comparison of ectopic gene expression methods in rat neural stem cells.

Neural stem cells (NSCs) have the ability to proliferate and differentiate into various types of cells that compose the nervous system. To study functions of genes in stem cell biology, genes or siRNAs need to be transfected. However, it is difficult to transfect ectopic genes into NSCs. Thus to identify the suitable method to achieve high transfection efficiency, we compared lipid transfection, electroporation, nucleofection and retroviral transduction. Among the methods that we tested, we found that nucleofection and retroviral transduction showed significantly increased transfection efficiency. In addition, with retroviral transduction of Ngn2 that is known to induce neurogenesis in various types of cells, we observed facilitated final cell division in rat NSCs. These data suggest that nucleofection and retroviral transduction provide high efficiency of gene delivery system to study functions of genes in rat NSCs.

Spectroscopic and chromatographic characterization of wastewater organic matter from a biological treatment plant.

Spectroscopic and chromatographic changes in dissolved organic matter (DOM) characteristics of influent and treated sewage were investigated for a wastewater treatment plant (WWTP) with a biological advanced process. Refractory DOM (R-DOM) was defined as the dissolved organic carbon concentrations of the samples after 28-day incubation for this study. Specific UV absorbance (SUVA), hydrophobicity, synchronous fluorescence spectra and molecular weight (MW) distributions were selected as DOM characteristics. The percent distribution of R-DOM for the effluent was much higher than that of the influent, indicating that biodegradable DOM was selectively removed during the process. Comparison of the influent versus the effluent sewage revealed that SUVA, fulvic-like fluorescence (FLF), humic-like fluorescence (HLF), the apparent MW values were enhanced during the treatment. This suggests that more aromatic and humic-like compounds were enriched during the biological process. No significant difference in the DOM characteristics was observed between the original effluent (i.e., prior to the incubation) and the influent sewage after the incubation. This result suggests that the major changes in wastewater DOM characteristics occurring during the biological advanced process were similar to those for simple microbial incubation.

Microbial transformation of dissolved leaf litter organic matter and its effects on selected organic matter operational descriptors.

Changes in selected spectroscopic and chromatographic characteristics of water-soluble organic matter (WSOM) extracted from leaf litter and its ability to bind pyrene were monitored throughout 14 day microbial incubation experiments. To provide additional insight into the microbial transformation of the WSOM, incubation experiments were similarly conducted with controlled-composition mixtures of glucose and dissolved humic substances (HS) that were base extracted from the same leaf litter source. Microbial transformation increased the specific ultraviolet absorbance and number-average molecular weight of residual WSOM while polydispersity values decreased. Fluorescence measurements revealed loss of protein-like fluorescence and enhancement of fulvic- and humic-like fluorescence in residual WSOM. Overall, the incubation results suggest that nonaromatic and smaller sized carbon structures were being degraded while the microbial activity produced humic-like aromatic components in solution. Together, these changes resulted in enhanced pyrene binding by the altered WSOM. Consistent findings resulted from mixtures of glucose and the leaf litter HS. Changes in measured operational descriptors were more pronounced for mixtures containing a higher percentage of glucose, suggesting that utilization of labile constituents may be necessary for formation of unknown structures associated with high pyrene binding capabilities. Simple mass balance, end member mixing models often failed to predict changes in pyrene binding brought about by microbial transformation, suggesting that microbial utilization of labile constituents is not the predominant process governing the enhanced pyrene binding.