This study aimed to analyze the eluted components of syringe-type bis-acryl composites and to evaluate the effect of removing the oxygen-inhibited layer on cytotoxicity. Four different bis-acryl provisional composite materials-Protemp 4 (PT), Structur 2 SC (ST), Luxatemp Automix Plus (LT), and Hexa-Temp (HT)-were evaluated. Gas chromatography/mass spectrometry was used to analyze the composite eluate after 24 h of immersion in methanol. An agar overlay test and a live/dead assay were performed on the polymerized disc-shaped specimens after 24 h. To evaluate the effect of removing the oxygen-inhibited layer, samples were prepared with a surface oxygen-inhibited layer. The surface oxygen-inhibited layer of the disc-shaped specimens was removed with alcohol only (subgroup A) or with polishing and alcohol (subgroup PA), and their cytotoxicities were compared with those of “as received” (subgroup N) specimens using the WST-1 assay. Statistical significance was assessed using analyses of variance, followed by Bonferroni multiple comparison tests (α=0.05). Different components were detected by gas chromatography/mass spectrometry analysis among the groups. The agar overlay assay confirmed severe cytotoxicity in HT, LT, and ST groups, whereas PT showed moderate cytotoxicity. The effect of removing the oxygen-inhibited layer on cell viability was significantly higher in PA than in N in all composite groups. In HT and ST, the cell viability was significantly higher in PA than in A. Syringe-type bis-acryl composites for provisional restorations may elute various components into the oral cavity, which may cause cytotoxicity in adjacent structures. The cytotoxicity of the materials is reduced by the removal of the oxygen-inhibited layer.

BRAF inhibitors (e.g., vemurafenib) are widely used to treat metastatic melanoma with the BRAF V600E mutation. The initial response is often dramatic, but treatment resistance leads to disease progression in the majority of cases. Although secondary mutations in the mitogen-activated protein kinase signaling pathway are known to be responsible for this phenomenon, the molecular mechanisms governing acquired resistance are not known in more than half of patients. Here we report a genome- and transcriptome-wide study investigating the molecular mechanisms of acquired resistance to BRAF inhibitors. A microfluidic chip with a concentration gradient of vemurafenib was utilized to rapidly obtain therapy-resistant clones from two melanoma cell lines with the BRAF V600E mutation (A375 and SK-MEL-28). Exome and transcriptome data were produced from 13 resistant clones and analyzed to identify secondary mutations and gene expression changes. Various mechanisms, including phenotype switching and metabolic reprogramming, have been determined to contribute to resistance development differently for each clone. The roles of microphthalmia-associated transcription factor, the master transcription factor in melanocyte differentiation/dedifferentiation, were highlighted in terms of phenotype switching. Our study provides an omics-based comprehensive overview of the molecular mechanisms governing acquired resistance to BRAF inhibitor therapy.

The Korean government’s strategy to combat coronavirus disease 2019 (COVID-19) has focused on non-pharmaceutical interventions, such as social distancing and wearing masks, along with testing, tracing, and treatment; overall, its performance has been relatively good compared to that of many other countries heavily affected by COVID-19. However, little attention has been paid to health equity in measures to control the COVID-19 pandemic. The study aimed to examine the unequal impacts of COVID-19 across socioeconomic groups and to suggest potential solutions to tackle these inequalities. The pathways linking social determinants and health could be entry points to tackle the unequal consequences of this public health emergency. It is crucial for infectious disease policy to consider social determinants of health including poor housing, precarious working conditions, disrupted healthcare services, and suspension of social services. Moreover, the high levels of uncertainty and complexity inherent in this public health emergency, as well as the health and socioeconomic inequalities caused by the pandemic, underscore the need for good governance other than top-down measures by the government. We emphasize that a people-centered perspective is a key approach during the pandemic era. Mutual trust between the state and civil society, strong accountability of the government, and civic participation are essential components of cooperative disaster governance.

BRAF inhibitors (e.g., vemurafenib) are widely used to treat metastatic melanoma with the BRAF V600E mutation. The initial response is often dramatic, but treatment resistance leads to disease progression in the majority of cases. Although secondary mutations in the mitogen-activated protein kinase signaling pathway are known to be responsible for this phenomenon, the molecular mechanisms governing acquired resistance are not known in more than half of patients. Here we report a genome- and transcriptome-wide study investigating the molecular mechanisms of acquired resistance to BRAF inhibitors. A microfluidic chip with a concentration gradient of vemurafenib was utilized to rapidly obtain therapy-resistant clones from two melanoma cell lines with the BRAF V600E mutation (A375 and SK-MEL-28). Exome and transcriptome data were produced from 13 resistant clones and analyzed to identify secondary mutations and gene expression changes. Various mechanisms, including phenotype switching and metabolic reprogramming, have been determined to contribute to resistance development differently for each clone. The roles of microphthalmia-associated transcription factor, the master transcription factor in melanocyte differentiation/dedifferentiation, were highlighted in terms of phenotype switching. Our study provides an omics-based comprehensive overview of the molecular mechanisms governing acquired resistance to BRAF inhibitor therapy.

Background: Unmet healthcare needs have many advantages for measuring inequalities in healthcare use. However, the existing indicator is difficult to capture the reality of unmet healthcare needs sufficiently and is not quite appropriate in comparing regional inequality. The purpose of this study is to critically analyze the utilization of the unmet healthcare need indicator for regional healthcare inequalities research. Methods: We used the level of healthcare accessibility and healthcare need to categorize the regions that are known to cause differences in healthcare utilization between regions and verified how existing unmet healthcare need indicator is distributed at the regional level. Results: Four types of regions were classified according to the high and low levels of healthcare needs and accessibility. The hypothesis about the regional type expected to have the highest unmet healthcare need was not proved. The hypothesis about the lowest expected regional type was proved, but the difference in the average rate of unmet healthcare needs among regional types was not significant. The standard deviation of the rate of unmet healthcare needs among regions within the same type was also higher than the overall regional variation, which also disproved the whole frame of hypothesis. Conclusion Failure to prove the hypothesis means the gap between the supposed meaning of the indicator and the reality. In order to understand the current state of healthcare utilization of people in various regions of Korea and to resolve inequality, fundamental research on the in-depth structure and mechanisms of healthcare utilization is needed.

Background: The fatality rate of patients with coronavirus disease 2019 (COVID-19) varies among countries owing to demographics, patient comorbidities, surge capacity of healthcare systems, and the quality of medical care. We assessed the clinical outcomes of patients with COVID-19 during the first wave of the epidemic in Korea. Methods: Using a modified World Health Organization clinical record form, we obtained clinical data for 3,060 patients with COVID-19 treated at 55 hospitals in Korea. Disease severity scores were defined as: 1) no limitation of daily activities; 2) limitation of daily activities but no need for supplemental oxygen; 3) supplemental oxygen via nasal cannula; 4) supplemental oxygen via facial mask; 5) non-invasive mechanical ventilation; 6) invasive mechanical ventilation; 7) multi-organ failure or extracorporeal membrane oxygenation therapy; and 8) death. Recovery was defined as a severity score of 1 or 2, or discharge and release from isolation. Results: The median age of the patients was 43 years of age; 43.6% were male. The median time from illness onset to admission was 5 days. Of the patients with a disease severity score of 3–4 on admission, 65 (71.5%) of the 91 patients recovered, and 7 (7.7%) died due to illness by day 28. Of the patients with disease severity scores of 5–7, 7 (19.5%) of the 36 patients recovered, and 8 (22.2%) died due to illness by day 28. None of the 1,324 patients who were < 50 years of age died; in contrast, the fatality rate due to illness by day 28 was 0.5% (2/375), 0.9% (2/215), 5.8% (6/104), and 14.0% (7/50) for the patients aged 50–59, 60–69, 70–79, and ≥ 80 years of age, respectively. Conclusion In Korea, almost all patients of < 50 years of age with COVID-19 recovered without supplemental oxygen. In patients of ≥ 50 years of age, the fatality rate increased with age, reaching 14% in patients of ≥ 80 years of age.

Purpose: This study aimed to explore turnover rates for Korean acute care hospital nurses and identify factors influencing their turnover. Methods: The study was retrospective in nature. Nurse cohort data were obtained from hospital status data from Korea's Health Insurance Review Assessment Service. The observation period was from January 1, 2012 to December 31, 2016, and data for 96,158 nurses were analyzed. Independent variables included nurses' age and sex and hospital setting, type, ownership, and nurse staffing level. KaplaneMeier analysis was performed to estimate survival curves, and factors influencing turnover were analyzed using Cox's proportional hazard regression. Results: The cumulative turnover probability for all nurses was .17, .29, .38, .45, and .50 for the first, second, third, fourth, and fifth years, respectively. The results showed that the longer the career duration, the lower the turnover rates. According to the factors influencing nurse turnover, both nurses' (i.e., sex and career duration) and hospitals' (i.e., hospital setting, type, ownership, and nurse staffing level) characteristics were statistically significant. Conclusion It should be noted that the turnover rate of nurses with less than three year of career duration and of those with less than one year has been shown to be quite high. Therefore, target populations for acute care hospital nurse turnover should be expanded from new graduate nurses to experienced nurses with less than 3 years of career. Further studies are required to examine the causes of high turnover rates in hospitals that are small and/or have low nurse staffing levels.

Purpose: This study aimed to explore turnover rates for Korean acute care hospital nurses and identify factors influencing their turnover. Methods: The study was retrospective in nature. Nurse cohort data were obtained from hospital status data from Korea's Health Insurance Review Assessment Service. The observation period was from January 1, 2012 to December 31, 2016, and data for 96,158 nurses were analyzed. Independent variables included nurses' age and sex and hospital setting, type, ownership, and nurse staffing level. KaplaneMeier analysis was performed to estimate survival curves, and factors influencing turnover were analyzed using Cox's proportional hazard regression. Results: The cumulative turnover probability for all nurses was .17, .29, .38, .45, and .50 for the first, second, third, fourth, and fifth years, respectively. The results showed that the longer the career duration, the lower the turnover rates. According to the factors influencing nurse turnover, both nurses' (i.e., sex and career duration) and hospitals' (i.e., hospital setting, type, ownership, and nurse staffing level) characteristics were statistically significant. Conclusion It should be noted that the turnover rate of nurses with less than three year of career duration and of those with less than one year has been shown to be quite high. Therefore, target populations for acute care hospital nurse turnover should be expanded from new graduate nurses to experienced nurses with less than 3 years of career. Further studies are required to examine the causes of high turnover rates in hospitals that are small and/or have low nurse staffing levels.

Characterizing the time course of baseline or pre-drug blood pressure is important in acquiring unbiased estimates of antihypertensive drug effect. In this study, we recruited 23 healthy male volunteers and measured systolic (SBP) and diastolic blood pressure (DBP) over 24 hours on an hourly basis. Using a non-linear mixed effects model, circadian rhythm observed in blood pressure measurements was described by incorporating two cosine functions with periods 24 and 12 hours. A mixture model was applied to identify subgroups exhibiting qualitatively different circadian rhythms. Our results suggested that 78% of the study population, defined as ‘dippers’, demonstrated a typical circadian profile with a morning rise and a nocturnal dip. The remaining 22% of the subjects defined as ‘non-dippers’, however, were not adequately described using the typical profile and demonstrated an elevation of blood pressure during night-time. Covariate search identified weight as being positively correlated with mesor of SBP. Visual predictive checks using 1,000 simulated datasets were performed for model validation. Observations were in agreement with predicted values in ‘dippers’, but deviated slightly in ‘non-dippers’. Our work is expected to serve as a useful reference in assessing systematic intra-day blood pressure fluctuations and antihypertensive effects as well as assessing drug safety of incrementally modified drugs.
Blood Pressure ; Circadian Rhythm ; Dataset ; Humans ; Male ; Volunteers

Peroxiredoxin (Prx), a family of ubiquitous thiol peroxidases, functions as a redox signaling regulator that controls cellular Hâ‚‚Oâ‚‚ in mammalian cells and has recently received attention for being overexpressed in various cancer types. In this study, we show that Prx type II (PrxII) is rather silenced in gastric cancer cells. PrxII expression is severely downregulated in 9 out of the 28 gastric cancer cell lines. Strikingly, PrxII expression is completely lost in three cell lines, MKN28, MKN74 and SNU484. Loss of PrxII expression is due to DNA methyltransferase 1-dependent methylation at the promoter region of the PrxII gene. Restoration of PrxII expression using a retroviral system markedly reduces the colony-forming ability and migratory activity of both MKN28 and SNU484 cells by inhibiting Src kinase. Mechanistically, PrxII peroxidase activity is essential for regulating gastric cancer cell migration. Bioinformatics analysis from The Cancer Genome Atlas stomach cancer data (STAD) revealed significantly low PrxII expression in gastric cancer patients and a negative correlation between PrxII expression and methylation levels. More importantly, low PrxII expression also strongly correlates with poor survival in cancer patients. Thus our study suggests that PrxII may be the first thiol peroxidase that simultaneously regulates both survival and metastasis in gastric cancer cells with high clinical relevance.