Accurately Modeling RNA Stem-Loops in an Implicit Solvent Environment.

Ribonucleic acid (RNA) molecules can adopt a variety of secondary and tertiary structures in solution, with stem-loops being one of the more common motifs. Here, we present a systematic analysis of 15 RNA stem-loop sequences simulated with molecular dynamics simulations in an implicit solvent environment. Analysis of RNA cluster ensembles showed that the stem-loop structures can generally adopt the A-form RNA in the stem region. Loop structures are more sensitive, and experimental structures could only be reproduced with modification of CH···O interactions in the force field, combined with an implicit solvent nonpolar correction to better model base stacking interactions. Accurately modeling RNA with current atomistic physics-based models remains challenging, but the RNA systems studied herein may provide a useful benchmark set for testing other RNA modeling methods in the future.

Air quality and kidney health: Assessing the effects of PM10, PM2.5, CO, and NO2 on renal function in primary glomerulonephritis.

BACKGROUND: While extensive studies have elucidated the relationships between exposure to air pollution and chronic diseases, such as cardiovascular disorders and diabetes, the intricate effects on specific kidney diseases, notably primary glomerulonephritis (GN)-an immune-mediated kidney ailment-are less well understood. Considering the escalating incidence of GN and conspicuous lack of investigative focus on its association with air quality, investigation is dedicated to examining the long-term effects of air pollutants on renal function in individuals diagnosed with primary GN. METHODS: This retrospective cohort analysis was conducted on 1394 primary GN patients who were diagnosed at Seoul National University Bundang Hospital and Seoul National University Hospital. Utilizing time-varying Cox regression and linear mixed models (LMM), we examined the effect of yearly average air pollution levels on renal function deterioration (RFD) and change in estimated glomerular filtration rate (eGFR). In this context, RFD is defined as sustained eGFR of less than 60 mL/min per 1.73 m2. RESULTS: During a mean observation period of 5.1 years, 350 participants developed RFD. Significantly, elevated interquartile range (IQR) levels of air pollutants-including PM10 (particles ≤10 micrometers, HR 1.389, 95 % CI 1.2-1.606), PM2.5 (particles ≤2.5 micrometers, HR 1.353, 95 % CI 1.162-1.575), CO (carbon monoxide, HR 1.264, 95 % CI 1.102-1.451), and NO2 (nitrogen dioxide, HR 1.179, 95 % CI 1.021-1.361)-were significantly associated with an increased risk of RFD, after factoring in demographic and health variables. Moreover, exposure to PM10 and PM2.5 was associated with decreased eGFR. CONCLUSIONS: This study demonstrates a substantial link between air pollution exposure and renal function impairment in primary GN, accentuating the significance of environmental determinants in the pathology of immune-mediated kidney diseases.

Association between systemic inflammation biomarkers and mortality in patients with sepsis-associated acute kidney injury receiving intensive care and continuous kidney replacement therapy: results from the RENERGY (REsearches for NEphRology and epidemioloGY) study.

BACKGROUND: Identifying risk factors and improving prognostication for mortality among patients with sepsis-associated acute kidney injury (AKI) undergoing continuous kidney replacement therapy (CKRT) is important in improving the adverse prognosis of this patient population. This study aimed to compare the prognostic value of existing systemic inflammation biomarkers and determine the optimal systemic inflammation biomarker in patients with sepsis-associated AKI receiving CKRT. METHODS: This multi-center, retrospective, observational cohort study included 1,500 patients with sepsis-associated AKI treated with intensive care and CKRT. The main predictor was a panel of 13 different systemic inflammation biomarkers. The primary outcome was 28-day mortality after CKRT initiation. Secondary outcomes included 90-day mortality after CKRT initiation, CKRT duration, kidney replacement therapy dependence at discharge, and lengths of intensive care unit (ICU) and hospital stays. RESULTS: When added to the widely accepted Acute Physiology and Chronic Health Evaluation II score, platelet-to-albumin ratio (PAR) and neutrophil-platelet score (NPS) had the highest improvements in prognostication of 28-day mortality, where the corresponding increases in C-statistic were 0.01 (95% confidence interval [CI], 0.00-0.02) and 0.02 (95% CI, 0.01-0.03). Similar findings were observed for 90-day mortality. The 28- and 90-day mortality rates were significantly lower for the higher PAR and NPS quartiles. These associations remained significant even after adjustment for potential confounding variables in multivariable Cox proportional hazards models. CONCLUSION: Of the available systemic inflammation biomarkers, the addition of PAR or NPS to conventional ICU prediction models improved the prognostication of patients with sepsis-associated AKI receiving intensive care and CKRT.

Phosphate level predicts mortality in acute kidney injury patients undergoing continuous kidney replacement therapy and has a U-shaped association with mortality in patients with high disease severity: a multicenter retrospective study.

BACKGROUND: This study investigated the association between serum phosphate level and mortality in acute kidney injury (AKI) patients undergoing continuous kidney replacement therapy (CKRT) and evaluated whether this association differed according to disease severity. METHODS: Data from eight tertiary hospitals in Korea were retrospectively analyzed. The patients were classified into four groups (low, normal, high, and very high) based on their serum phosphate level at baseline. The association between serum phosphate level and mortality was then analyzed, with further subgroup analysis being conducted according to disease severity. RESULTS: Among the 3,290 patients identified, 166, 955, 1,307, and 862 were in the low, normal, high, and very high phosphate groups, respectively. The 90-day mortality rate was 63.9% and was highest in the very high group (76.3%). Both the high and very high groups showed a significantly higher 90-day mortality rate than did the normal phosphate group (high: hazard ratio [HR], 1.35, 95% confidence interval [CI], 1.21-1.51, p < 0.001; very high: HR, 2.01, 95% CI, 1.78-2.27, p < 0.001). The low group also exhibited a higher 90-day mortality rate than did the normal group among those with high disease severity (HR, 1.47; 95% CI, 1.09-1.99; p = 0.01) but not among those with low disease severity. CONCLUSION: High serum phosphate level predicted increased mortality in AKI patients undergoing CKRT, and low phosphate level was associated with increased mortality in patients with high disease severity. Therefore, serum phosphate levels should be carefully considered in critically ill patients with AKI.

Reactivation of Varicella-Zoster Virus in Patients with Lung Cancer Receiving Immune Checkpoint Inhibitors: Retrospective Nationwide Population-Based Cohort Study from South Korea.

BACKGROUND: This study aimed to determine the association between immune checkpoint inhibitors (ICIs) and the risk of herpes zoster (HZ) incidence in patients with lung cancer. METHOD: We obtained national claims data of 51,021 patients from South Korea with lung cancer between August 2017 and December 2021. The study population was classified into ICI and non-ICI groups based on the prescription of ICIs at least once during the study period. To estimate the effects of ICIs treatment compared with those without ICIs treatment on HZ incidence, we used the Cox proportional hazards model adjusted for sex, age, comorbidities, and concomitant use of immunosuppressive drugs. Stratified analyses based on sex, age, and comorbidities were conducted to identify corresponding risk factors. RESULTS: Of the 51,021 study participants, 897 (1.8%) were prescribed ICIs and 2262 (4.4%) were diagnosed with HZ. Approximately 75.6% of the patients receiving ICIs were male, and the prevalence of diabetes, cardiovascular disease, and chronic lung disease in the ICI group was significantly lower than that in the non-ICIs group. The Kaplan-Meier plot showed that the probability of incidence of HZ in the ICIs group was lower than that in the non-ICIs group. Additionally, treatment with ICIs was associated with a 31% lower incidence of developing HZ when compared to that seen without ICIs treatment (95% confidence interval [CI], 0.48-1.00). This association was stronger in females (hazard ratio [HR], 0.42; 95% CI, 0.19-0.94) and those less than 68 years of age (HR, 0.58; 95% CI, 0.34-0.99). CONCLUSIONS: In these real-world data from an Asian population with lung cancer, ICIs treatment might be associated with a reduced risk of HZ compared to that without ICIs treatment.

Long-term ozone exposure and mortality in patients with chronic kidney disease: a large cohort study.

BACKGROUND: Epidemiologic studies on the effects of long-term exposure to ozone (O3) have shown inconclusive results. It is unclear whether to O3 has an effect on chronic kidney disease (CKD). We investigated the effects of O3 on mortality and renal outcome in CKD. METHODS: We included 61,073 participants and applied Cox proportional hazards models to examine the effects of ozone on the risk of end-stage renal disease (ESRD) and mortality in a two-pollutants model adjusted for socioeconomic status. We calculated the concentration of ozone exposure one year before enrollment and used inverse distance weighting (IDW) for interpolation, where the exposure was evenly distributed. RESULTS: In the single pollutant model, O3 was significantly associated with an increased risk of ESRD and all-cause mortality. Based on the O3 concentration from IDW interpolation, this moving O3 average was significantly associated with an increased risk of ESRD and all-cause mortality. In a two-pollutants model, even after we adjusted for other measured pollutants, nitrogen dioxide did not attenuate the result for O3. The hazard ratio (HR) value for the district-level assessment is 1.025 with a 95% confidence interval (CI) of 1.014-1.035, while for the point-level assessment, the HR value is 1.04 with a 95% CI of 1.035-1.045. The impact of ozone on ESRD, hazard ratio (HR) values are, 1.049(95%CI: 1.044-1.054) at the district unit and 1.04 (95%CI: 1.031-1.05) at the individual address of the exposure assessment. The ozone hazard ratio for all-cause mortality was 1.012 (95% confidence interval: 1.008-1.017) for administrative districts and 1.04 (95% confidence interval: 1.031-1.05) for individual addresses. CONCLUSIONS: This study suggests that long-term ambient O3 increases the risk of ESRD and mortality in CKD. The strategy to decrease O3 emissions will substantially benefit health and the environment.

A Comparison of Health Risks from PM2.5 and Heavy Metal Exposure in Industrial Complexes in Dangjin and Yeosu·Gwangyang.

Particulate matter (PM) can cause illness, including respiratory diseases, and PM2.5 compositions are likely to vary according to the emission profiles of industrial complexes. This study analyzed and compared the concentrations and distributions of PM2.5 and heavy metals in two regions of Republic of Korea: Yeosu·Gwangyang, which houses a massive national industrial complex, and Dangjin, which houses power plants. Further, we conducted a health risk assessment on the residents of the areas near these industrial complexes. Measurements were taken at five different points in each setting over a two-year period from August 2020 to August 2022. We found differences in PM2.5 concentrations and heavy metal composition ratios across the sites. Specifically, PM2.5 concentrations exceeded the standard of 1 at all measurement sites, while the specific heavy metals exceeding the standard varied across the sites. Ultimately, we observed regional differences in PM2.5 composition across measurement sites across and within the two regions and variations in health risks and according health effects due to the absence of PM2.5 toxicity values, and compared the health risks of two industrial complexes with different characteristics. These findings underscore the importance of considering not only PM2.5 but also its composition in exposure and health risk assessments.

Association of metformin with cardiovascular and graft outcomes in kidney transplant recipients with posttransplantation diabetes mellitus.

Background: Posttransplantation diabetes mellitus (PTDM) is a crucial problem after kidney transplantation. We aimed to determine whether metformin affects cardiovascular and graft outcomes in patients with PTDM. Methods: This retrospective cohort study included 1,663 kidney transplant recipients without preexisting diabetes mellitus. The patients were divided into metformin and non-metformin groups, with matched propensity scores. We also estimated metformin's effect on percutaneous coronary intervention (PCI), major adverse cardiovascular events (MACEs), acute rejection, and graft failure. Results: Of 634 recipients with PTDM, 406 recipients were treated with metformin. The incidence of PCI was 2.4% and 7.1% in the metformin and non-metformin groups, respectively (p = 0.04). The metformin group exhibited a lower risk of PCI in Cox regression analyses (hazard ratio [HR], 0.27; 95% confidence interval [CI], 0.10-0.77; p = 0.014), especially in subgroups with male sex, age over 49 years (median), long-term metformin use (mean of ≥1,729 days), and simultaneous tacrolimus administration. Long-term metformin use was also associated with lower incidence of MACEs (HR, 0.09; 95% CI, 0.01-0.67; p = 0.02). Incidence of graft failure was 9.9% and 17.0% in the metformin and non-metformin groups, respectively (p = 0.046). Both long-term use and higher dose of metformin, as well as tacrolimus administration with metformin, were associated with a lower risk of graft failure (HR, 0.29; 95% CI, 0.11-0.75; p = 0.01; HR, 0.39; 95% CI, 0.18-0.85; p = 0.02; and HR, 0.39; 95% CI, 0.19-0.79; p = 0.009, respectively). Conclusion: Metformin use is associated with a decreased risk of developing coronary artery disease and better graft outcomes in PTDM.

Short-term exposure to ambient air pollution and injuries due to external causes according to intentions and mechanisms.

Although injuries are a leading cause of death and affect the life expectancy of individuals who live with disabilities globally, the potential role of air pollution exposure on injuries due to external causes has received little scientific attention, especially compared with that given to the association of air pollution and non-external causes of morbidity and mortality. We investigated the association between emergency department visits for externally caused injuries and short-term exposure to major ambient air pollutants, with focus on the intentions and mechanisms of injuries. We identified 2,049,855 injured patients in Seoul, South Korea between 2008 and 2016 using the National Emergency Database. Daily short-term exposure to air pollution including particles <10 µm (PM10) and <2.5 µm (PM2.5), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and ozone (O3) was estimated based on hourly concentrations. We employed a time-stratified case-crossover study design using a conditional Poisson regression model adjusted for meteorological variables, influenza epidemics, and holidays. Immediate exposure (lag 0) to most pollutants significantly increased the risk of total injuries (PM2.5, 0.42 %; NO2, 0.68 %; SO2, 1.05 %; CO, 0.57 %; O3, 1.86 % per interquartile range increment), and the associations differed according to the intention and mechanism of injury. Unintentional and assault injuries were significantly associated with air pollution exposure, whereas self-harm injuries showed no association. In mechanism-specific analyses, injuries caused by falls, blunt objects, penetration, traffic accidents, machinery, and slips were associated with specific air pollutants, even in the co-pollutant models. The associations were stronger in injured patients aged <15 years, and in males than in their counterparts. Our results suggest that short-term air pollution exposure might play a role in the risk of externally caused injuries and the association may differ depending on the intention and mechanism of injury, which provide important evidence for injury prevention and air quality strategies.

The impact of C-reactive protein-to-albumin ratio on mortality in patients with acute kidney injury requiring continuous renal replacement therapy: A multicenter retrospective study.

INTRODUCTION: C-reactive protein-to-albumin ratio (CAR) is a prognostic marker in various diseases that represents patients' inflammation and nutritional status. Here, we aimed to investigate the prognostic value of CAR in critically ill patients with severe acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). METHODS: We retrospectively collected data from eight tertiary hospitals in Korea from 2006-2021. The patients were divided into quartiles according to CAR levels at the time of CRRT initiation. Cox regression analyses were performed to investigate the effect of CAR on in-hospital mortality. The mortality prediction performance of CAR was evaluated using the area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: In total, 3995 patients who underwent CRRT were included, and the in-hospital mortality rate was 67.3% during the follow-up period. The 7-day, 30-day, and in-hospital mortality rates increased toward higher CAR quartiles (all P < 0.001). After adjusting for confounding variables, the higher quartile groups had an increased risk of in-hospital mortality (quartile 3: adjusted hazard ratio [aHR], 1.26, 95% confidence interval [CI], 1.10-1.43, P < 0.001; quartile 4: aHR, 1.22, 95% CI, 1.07-1.40, P = 0.003). CAR combined with APACHE II or SOFA scores significantly increased the predictive power compared to each severity score alone for the AUC, NRI, and IDI (all P < 0.05). CONCLUSIONS: A high CAR is associated with increased in-hospital mortality in critically ill patients requiring CRRT. The combined use of CAR and severity scores provides better predictive performance for mortality than the severity score alone.

The effects of muscle mass and quality on mortality of patients with acute kidney injury requiring continuous renal replacement therapy.

This study examined the effects of muscle mass on mortality in patients with acute kidney injury requiring continuous renal replacement therapy. It was conducted in eight medical centers between 2006 and 2021. The data of 2200 patients over the age of 18 years with acute kidney injury who required continuous renal replacement therapy were retrospectively collected. Skeletal muscle areas, categorized into normal and low attenuation muscle areas, were obtained from computed tomography images at the level of the third lumbar vertebra. Cox proportional hazards models were used to investigate the association between mortality within 1, 3, and 30 days and skeletal muscle index. Sixty percent of patients were male, and the 30-day mortality rate was 52%. Increased skeletal muscle areas/body mass index was associated with decreased mortality risk. We also identified a 26% decreased risk of low attenuation muscle area/body mass index on mortality. We established that muscle mass had protective effects on the mortality of patients with acute kidney injury requiring continuous renal replacement therapy. This study showed that muscle mass is a significant determinant of mortality, even if the density is low.

Dynamic nature and prognostic value of the neutrophil-to-lymphocyte ratio in critically ill patients with acute kidney injury on continuous renal replacement therapy: A multicenter cohort study.

Introduction: Patients with acute kidney injury (AKI) receiving renal replacement therapy constitute the subgroup of AKI with the highest risk of mortality. Despite recent promising findings on the neutrophil-to-lymphocyte ratio (NLR) in AKI, studies have not yet addressed the clinical implication of the NLR in this population. Therefore, we aimed to examine the prognostic value of NLR in critically ill patients requiring continuous renal replacement therapy (CRRT), especially focusing on temporal changes in NLR. Methods: We enrolled 1,494 patients with AKI who received CRRT in five university hospitals in Korea between 2006 and 2021. NLR fold changes were calculated as the NLR on each day divided by the NLR value on the first day. We performed a multivariable Cox proportional hazard analysis to assess the association between the NLR fold change and 30-day mortality. Results: The NLR on day 1 did not differ between survivors and non-survivors; however, the NLR fold change on day 5 was significantly different. The highest quartile of NLR fold change during the first 5 days after CRRT initiation showed a significantly increased risk of death (hazard ratio [HR], 1.65; 95% confidence intervals (CI), 1.27-2.15) compared to the lowest quartile. NLR fold change as a continuous variable was an independent predictor of 30-day mortality (HR, 1.14; 95% CI, 1.05-1.23). Conclusion: In this study, we demonstrated an independent association between changes in NLR and mortality during the initial phase of CRRT in AKI patients receiving CRRT. Our findings provide evidence for the predictive role of changes in the NLR in this high-risk subgroup of AKI.

Long-term exposure to particulate air pollution and incidence of Parkinson's disease: A nationwide population-based cohort study in South Korea.

There has been increasing interest in the neurological impact of particulate matter (PM). However, its association with the incidence of Parkinson's disease (PD) remains unclear. We selected 313,355 participants satisfying inclusion criteria from the National Health Insurance Service-National Sample Cohort based on the nationwide population of South Korea, and followed them up from January 2007 through December 2015. Individual-level long-term PM exposure was assessed as the five time-varying average concentrations estimated for the previous 1, 2, 3, 4 and 5 years on each year (until censored or event occurred) at the district-level residential addresses of participants using a previously validated prediction model. Incident PD was defined as the first diagnosis accompanied by anti-PD medication prescription from 2007 through 2015. Time-varying Cox proportional hazards models were employed to estimate the hazard ratio (HR) of incident PD for long-term PM exposure, adjusting for individual- and area-level covariates. During the 8 years (2,745,389 person-years) of follow-up for a total of 313,355 participants (mean [range] age, 48.9 [19-87] years; 169,571 males [54.1%]), 2621 participants (0.8%) developed PD. The HR of incident PD per interquartile range (3.3 µg/m3) increase in fine PM (PM2.5) for the previous 1 year was 1.08 (95% confidence interval: 1.01-1.19). In subgroup-specific analyses, HRs for PM2.5 were significant among older participants, males, participants living in metropolitan cities, ibuprofen users, and participants with comorbidities (HR: 1.10-1.20). Long-term exposure to PM2.5 might play a role in PD development.

Association between Residential Greenness and Incidence of Parkinson's Disease: A Population-Based Cohort Study in South Korea.

It is widely known that exposure to residential greenness is beneficial for health. However, few studies have analyzed the association between greenery and Parkinson's disease (PD). We selected 313,355 participants who matched the inclusion criteria from the National Health Insurance Service-National Sample Cohort, followed up from 2007 to 2015. Residential greenness, represented by the normalized difference vegetation index (NDVI), was obtained from satellite measurements. We estimated hazard ratios of PD associated with a 0.1-unit increase in long-term greenness exposure at the district level for the previous 1 year of each year until a censoring/event occurred, using time-varying Cox proportional hazard models, adjusted for individual- and area-level characteristics. During the 2,745,389 person-years of follow-up, 2621(0.8%) participants developed PD. Exposure to higher levels of residential greenness was found to be associated with a decreased risk of PD incidence (21% per 0.1-unit increase, 95% confidence interval (CI): 0.74-0.84). In subgroup analyses, stronger protective effects were observed in participants aged over 50 years, females, overweight/obese participants, non-urban residents, non-smokers, alcoholics, and those with comorbidities. Long-term exposure to greenness was beneficial to incident PD, and our findings could aid in the development of public-health strategies.

Recalibration and validation of the Charlson Comorbidity Index in acute kidney injury patients underwent continuous renal replacement therapy.

BACKGROUND: Comorbid conditions impact the survival of patients with severe acute kidney injury (AKI) who require continuous renal replacement therapy (CRRT). The weights assigned to comorbidities in predicting survival vary based on type of index, disease, and advances in management of comorbidities. We developed a modified Charlson Comorbidity Index (CCI) for use in patients with AKI requiring CRRT (mCCI-CRRT) and improved the accuracy of risk stratification for mortality. METHODS: A total of 828 patients who received CRRT between 2008 and 2013, from three university hospital cohorts was included to develop the comorbidity score. The weights of the comorbidities were recalibrated using a Cox proportional hazards model adjusted for demographic and clinical information. The modified index was validated in a university hospital cohort (n = 919) using the data of patients treated from 2009 to 2015. RESULTS: Weights for dementia, peptic ulcer disease, any tumor, and metastatic solid tumor were used to recalibrate the mCCI-CRRT. Use of these calibrated weights achieved a 35.4% (95% confidence interval [CI], 22.1%-48.1%) higher performance than unadjusted CCI in reclassification based on continuous net reclassification improvement in logistic regression adjusted for age and sex. After additionally adjusting for hemoglobin and albumin, consistent results were found in risk reclassification, which improved by 35.9% (95% CI, 23.3%-48.5%). CONCLUSION: The mCCI-CRRT stratifies risk of mortality in AKI patients who require CRRT more accurately than does the original CCI, suggesting that it could serve as a preferred index for use in clinical practice.

Association between behavioral patterns and mortality among US adults: National Health and Nutrition Examination Survey, 2007-2014.

Few large-scale studies have been conducted to show the joint effects of mortality associated with physical activity and sedentarism. Therefore, we examined the relationship between all-cause mortality and behavioral patterns among adults in the United States. Data of 17,730 non-institutionalized US civilians aged ≥20 years were extracted from the 2007-2014 National Health and Nutrition Examination Survey. We set the criteria for metabolic equivalents as 600 according to the WHO guideline, and sedentary time as 300 min/day according to the median. The Cox proportional hazards model was adjusted for demographic and lifestyle characteristics. During the 58.54±28.18 months follow-up, all-cause mortality rate was 4% and heart-related and cancer mortality rate was 1%. Participants in the high metabolic equivalents and low sedentary time group had a lower risk of all-cause (hazard ratio = 0.41, 95% confidence interval = 0.34-0.50), cardiovascular (hazard ratio = 0.36; 95% confidence interval = 0.23-0.55), and cancer (hazard ratio = 0.55; 95% confidence interval = 0.37-0.83) mortality, compared to those in the low metabolic equivalents and high sedentary time group. Sufficient physical activity and less sedentary behavior reduce all-cause and cause-specific mortality in adults in the United States, especially cardiovascular mortality among the elderly. Additional nationwide policies to improve behavioral patterns among adults need to be implemented in the United States.

Burden of dust storms on years of life lost in Seoul, South Korea: A distributed lag analysis.

Although dust storms have been associated with adverse health outcomes, studies on the burden of dust storms on deaths are limited. As global warming has induced significant climate changes in recent decades, which have accelerated desertification worldwide, it is necessary to evaluate the burden of dust storm-induced premature mortality using a critical measure of disease burden, such as the years of life lost (YLL). The YLL attributable to dust storms have not been examined to date. This study investigated the association between Asian dust storms (ADS) and the YLL in Seoul, South Korea, during 2002-2013. We conducted a time-series study using a generalized additive model assuming a Gaussian distribution and applied a distributed lag model with a maximum lag of 5 days to investigate the delayed and cumulative effects of ADS on the YLL. We also conducted stratified analyses using the cause of death (respiratory and cardiovascular diseases) and sociodemographic status (sex, age, education level, occupation, and marital status). During the study period, 108 ADS events occurred, and the average daily YLL was 1511 years due to non-accidental causes. The cumulative ADS exposure over the 6-day lag period was associated with a significant increase of 104.7 (95% CI, 31.0-178.5 years) and 34.4 years (4.0-64.7 years) in the YLL due to non-accidental causes and cardiovascular mortality, respectively. Sociodemographic analyses revealed associations between ADS exposure and the YLL in males, both <65 and ≥ 65 years old, those with middle-level education, and the unemployed, unmarried, and widowed (26.5-83.8 years). This study provides new evidence suggesting that exposure to dust storms significantly increases the YLL. Our findings suggest that dust storms are a critical environmental risk affecting premature mortality. These results could contribute to the establishment of public health policies aimed at managing dust storm exposure and reducing premature deaths.

Plant-Expressed Receptor Binding Domain of the SARS-CoV-2 Spike Protein Elicits Humoral Immunity in Mice.

The current 15-month coronavirus disease-19 (COVID-19) pandemic caused by SARS-CoV-2 has accounted for 3.77 million deaths and enormous worldwide social and economic losses. A high volume of vaccine production is urgently required to eliminate COVID-19. Inexpensive and robust production platforms will improve the distribution of vaccines to resource-limited countries. Plant species offer such platforms, particularly through the production of recombinant proteins to serve as immunogens. To achieve this goal, here we expressed the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein in the glycoengineered-tobacco plant Nicotiana benthamiana to provide a candidate subunit vaccine. This recombinant RBD elicited humoral immunity in mice via induction of highly neutralizing antibodies. These findings provide a strong foundation to further advance the development of plant-expressed RBD antigens for use as an effective, safe, and inexpensive SARS-CoV-2 vaccine. Moreover, our study further highlights the utility of plant species for vaccine development.

Evaluation of the Prognosis of COVID-19 Patients According to the Presence of Underlying Diseases and Drug Treatment.

Certain underlying diseases such as diabetic mellitus and hypertension are a risk factor for the severity and mortality of coronavirus disease (COVID-19) patients. Furthermore, both angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) are controversial at role in the process of COVID-19 cases. The aim of the study was to investigate whether underlying diseases and taking ACEi/ARBs, affect the duration of hospitalization and mortality in patients with confirmed COVID-19. Medical usage claims data for the past three years until 15 May 2020, from the "CORONA-19 International Cooperation Research" project was used. We analyzed the medical insurance claims data for all 7590 coronavirus (COVID-19) patients confirmed by RT-PCR tests nationwide up to 15 May 2020. Among the comorbidities, a history of hypertension (hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.056-2.158) and diabetes (HR, 1.867; 95% CI, 1.408-2.475) were associated significantly with mortality. Furthermore, heart failure (HR, 1.391; 95% CI, 1.027-1.884), chronic obstructive pulmonary disease (HR, 1.615; 95% CI, 1.185-2.202), chronic kidney disease (HR, 1.451; 95% CI, 1.018-2.069), mental disorder (HR, 1.61; 95% CI, 1.106-2.343), end stage renal disease (HR, 5.353; 95% CI, 2.185-13.12) were also associated significantly with mortality. The underlying disease has increased the risk of mortality in patients with COVID-19. Diabetes, hypertension, cancer, chronic kidney disease, heart failure, and mental disorders increased mortality. Controversial whether taking ACEi/ARBs would benefit COVID-19 patients, in our study, patients taking ACEi/ARBs had a higher risk of mortality.

Effects of residential greenness on clinical outcomes of patients with chronic kidney disease: a large-scale observation study.

BACKGROUND: As industrialization and urbanization are accelerating, the distribution of green areas is decreasing, particularly in developing countries. Since the 2000s, the effects of surrounding greenness on self-perceived health, including physical and mental health, longevity, and obesity have been reported. However, the effects of surrounding green space on chronic kidney disease are not well understood. Therefore, we investigated the impact of residential greenness on the mortality of chronic kidney disease patients and progression from chronic kidney disease to end-stage renal disease (ESRD). METHODS: Using a large-scale observational study, we recruited chronic kidney disease patients (n = 64,565; mean age, 54.0 years; 49.0% of male) who visited three Korean medical centers between January 2001 and December 2016. We investigated the hazard ratios of clinical outcomes per 0.1-point increment of exposure to greenness using various models. RESULTS: During the mean follow-up of 6.8 ± 4.6 years, 5,512 chronic kidney disease patients developed ESRD (8.5%) and 8,543 died (13.2%). In addition, a 0.1-point increase in greenness reduced all-cause mortality risk in chronic kidney disease and ESRD patients and progression of chronic kidney disease to ESRD in a fully adjusted model. The association between mortality in ESRD patients and the normalized difference vegetation index was negatively correlated in people aged >65 years, who had normal weight, were nonsmokers, and lived in a nonmetropolitan area. CONCLUSION: Chronic kidney disease patients who live in areas with higher levels of greenness are at reduced risk of all-cause mortality and progression to ESRD.