Emergency department visits and hospital readmissions after a deprescribing intervention among hospitalized older adults.

BACKGROUND: Deprescribing is the planned/supervised method of dose reduction or cessation of medications that might be harmful, or no longer be beneficial. Though benefits of deprescribing are debatable in improving clinical outcomes, it has been associated with decreased number of potentially inappropriate medications, which may potentially reduce the risk of adverse events among hospitalized older adults. With unclear evidence for deprescribing in this population, this study aimed to examine time-to-first unplanned healthcare utilization, which included 90-day emergency department (ED) visits or hospital readmission and associated predictors, during a deprescribing intervention. METHODS: A secondary data analysis of a clinical trial (Shed-MEDS NCT02979353) was performed. Cox regression was used to compare the time-to-first 90-day ED visit/readmission/death from hospital discharge for the intervention and control groups. Additionally, we performed exploratory analysis of predictors (comorbidities, functional health status, drug burden index (DBI), hospital length of stay, health literacy, food insecurity, and financial burden) associated with the time-to-first 90-day ED visit/readmission/death. RESULTS: The hazard of first 90-day ED visits/readmissions/death was 15% lower in the intervention versus the control group (95% CI: 0.61-1.19, p = 0.352, respectively); however, this difference was not statistically significant. For every additional number of comorbidities (Hazard ratio (HR): 1.12, 95% CI: 1.04-1.21) and each additional day of hospital length of stay (HR: 1.04, 95% CI: 1.01-1.07) were significantly associated with a higher hazard of 90-day ED visit/readmission/death in the intervention group; whereas for each unit of increase in pre-hospital DBI score (HR: 1.08 and HR 1.16, respectively) was significantly associated with a higher hazard of 90-day ED visit/readmission/death in the control group. CONCLUSIONS: The intervention and control groups had comparable time-to-first 90-day ED visit/readmission/death during a deprescribing intervention. This finding suggests that deprescribing did not result in a higher risk of ED visit/readmission/death during the 90-day period following hospital discharge.

MiR-29 and MiR-140 regulate TRAIL-induced drug tolerance in lung cancer.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has chemotherapeutic potential as a regulator of an extrinsic apoptotic ligand, but its effect as a drug is limited by innate and acquired resistance. Recent findings suggest that an intermediate drug tolerance could mediate acquired resistance, which has made the main obstacle for limited utility of TRAIL as an anti-cancer therapeutics. We propose miRNA-dependent epigenetic modification drives the drug tolerant state in TRAIL-induced drug tolerant (TDT). Transcriptomic analysis revealed miR-29 target gene activation in TDT cells, showing oncogenic signature in lung cancer. Also, the restored TRAIL-sensitivity was associated with miR-29ac and 140-5p expressions, which is known as tumor suppressor by suppressing oncogenic protein RSK2 (p90 ribosomal S6 kinase), further confirmed in patient samples. Moreover, we extended this finding into 119 lung cancer cell lines from public data set, suggesting a significant correlation between TRAIL-sensitivity and RSK2 mRNA expression. Finally, we found that increased RSK2 mRNA is responsible for NF-κB activation, which we previously showed as a key determinant in both innate and acquired TRAIL-resistance. Our findings support further investigation of miR-29ac and -140-5p inhibition to maintain TRAIL-sensitivity and improve the durability of response to TRAIL in lung cancer.

Association between Consumption of Iodine-Rich Foods and Thyroid Cancer Prevalence: Findings from a Large Population-Based Study.

The influence of iodine-rich foods on thyroid cancer (TC) risk remains inadequately understood. Therefore, we aimed to comprehensively investigate the relationship between three iodine-rich food groups and TC prevalence using extensive data from a large Korean population. We assessed the dietary intake of 169,057 participants in the Korean Genome and Epidemiology Study (2004-2013) using a food frequency questionnaire. The top-three iodine-rich food groups (including egg, seaweed, and dairy) were selected based on Korean dietary reference intakes and categorized by weekly consumption frequency. We conducted multiple logistic regression models to examine the relationship between food consumption and TC prevalence. After adjusting for confounding factors, higher seaweed consumption (>5 times/week) was significantly associated with lower TC prevalence (odds ratio [OR], 95% confidence interval [CI] = 0.42, 0.32-0.56, p-value < 0.001). In contrast, compared with moderate dairy consumption (3-4 times/week), lower dairy product intake (<1 time/week) was associated with higher TC prevalence (OR, 95% CI = 1.32, 1.05-1.67, p-value = 0.017). Our findings suggest that sufficient seaweed consumption may offer protection against TC, and incorporating dairy products into the diet may lower TC incidence in the Korean population. The most significant limitations of our study are the absence of 24 h urine samples for iodine status assessment and the lack of clinical data on the diagnosis of thyroid cancer.

Testing the Reliability and Validity of the Korean Version of the Pittsburgh Sleep Quality Index Using Fitbit Devices: A Cross-Sectional Analysis.

Background: Sleep disorders and insomnia are prevalent worldwide, with negative health outcomes. The Pittsburgh Sleep Quality Index (PSQI) is a widely used self-report assessment tool for evaluating sleep quality, comprising seven subdomains. The Korean version of the PSQI (PSQI-K) has been tested for reliability and validity in small sample sizes but lacks large-scale validation using objective measures. Methods: This study was conducted with 268 Korean adults attending health check programs. Participants completed the PSQI-K questionnaire and wore Fitbit devices (Fitbit Inc., USA) to ascertain sleep parameters. Reliability was analyzed using the Cronbach's α coefficient, and construct validity was determined through factor analysis. Criteria validity was assessed by correlating their index scores with Fitbit sleep parameters. We identified the optimal cutoff for detecting sleep disorders. Results: The Cronbach's α coefficient was 0.61, indicating adequate internal consistency. Factor analysis revealed three factors, explaining 48.2% of sleep quality variance. The index scores were negatively correlated with Fitbit sleep efficiency, total sleep time, and number of awakenings (P<0.05). The optimal cutoff point for identifying sleep disorder groups was ≥6. Conclusion: The PSQI-K demonstrated good reliability and validity when correlated with Fitbit sleep parameters, offering a practical screening tool for identifying sleep disorders among Korean adults. Cutoff scores can help identify patients for sleep interventions. However, further large-scale studies are required to validate these findings.

Integrated clinical and genomic models using machine-learning methods to predict the efficacy of paclitaxel-based chemotherapy in patients with advanced gastric cancer.

BACKGROUND: Paclitaxel is commonly used as a second-line therapy for advanced gastric cancer (AGC). The decision to proceed with second-line chemotherapy and select an appropriate regimen is critical for vulnerable patients with AGC progressing after first-line chemotherapy. However, no predictive biomarkers exist to identify patients with AGC who would benefit from paclitaxel-based chemotherapy. METHODS: This study included 288 patients with AGC receiving second-line paclitaxel-based chemotherapy between 2017 and 2022 as part of the K-MASTER project, a nationwide government-funded precision medicine initiative. The data included clinical (age [young-onset vs. others], sex, histology [intestinal vs. diffuse type], prior trastuzumab use, duration of first-line chemotherapy), and genomic factors (pathogenic or likely pathogenic variants). Data were randomly divided into training and validation sets (0.8:0.2). Four machine learning (ML) methods, namely random forest (RF), logistic regression (LR), artificial neural network (ANN), and ANN with genetic embedding (ANN with GE), were used to develop the prediction model and validated in the validation sets. RESULTS: The median patient age was 64 years (range 25-91), and 65.6% of those were male. A total of 288 patients were divided into the training (n = 230) and validation (n = 58) sets. No significant differences existed in baseline characteristics between the training and validation sets. In the training set, the areas under the ROC curves (AUROC) for predicting better progression-free survival (PFS) with paclitaxel-based chemotherapy were 0.499, 0.679, 0.618, and 0.732 in the RF, LR, ANN, and ANN with GE models, respectively. The ANN with the GE model that achieved the highest AUROC recorded accuracy, sensitivity, specificity, and F1-score performance of 0.458, 0.912, 0.724, and 0.579, respectively. In the validation set, the ANN with GE model predicted that paclitaxel-sensitive patients had significantly longer PFS (median PFS 7.59 vs. 2.07 months, P = 0.020) and overall survival (OS) (median OS 14.70 vs. 7.50 months, P = 0.008). The LR model predicted that paclitaxel-sensitive patients showed a trend for longer PFS (median PFS 6.48 vs. 2.33 months, P = 0.078) and OS (median OS 12.20 vs. 8.61 months, P = 0.099). CONCLUSIONS: These ML models, integrated with clinical and genomic factors, offer the possibility to help identify patients with AGC who may benefit from paclitaxel chemotherapy.

Melosira nummuloides Ethanol Extract Ameliorates Alcohol-Induced Liver Injury by Affecting Metabolic Pathways.

Melosira nummuloides is a microalga with a nutritionally favorable polyunsaturated fatty acid profile. In the present study, M. nummuloides ethanol extract (MNE) was administered to chronic-binge alcohol-fed mice and alcohol-treated HepG2 cells, and its hepatoprotective effects and underlying mechanisms were investigated. MNE administration reduced triglyceride (TG), total cholesterol (T-CHO), and liver injury markers, including aspartate transaminase (AST) and alanine transaminase (ALT), in the serum of chronic-binge alcohol-fed mice. However, MNE administration increased the levels of phosphorylated adenosine monophosphate-activated protein kinase (P-AMPK/AMPK) and PPARα, which was accompanied by a decrease in SREBP-1; this indicates that MNE can inhibit adipogenesis and improve fatty acid oxidation. Moreover, MNE administration upregulated the expression of antioxidant enzymes, including SOD, NAD(P)H quinone dehydrogenase 1, and GPX, and ameliorated alcohol-induced inflammation by repressing the Akt/NFκB/COX-2 pathway. Metabolomic analysis revealed that MNE treatment modulated many lipid metabolites in alcohol-treated HepG2 cells. Our study findings provide evidence for the efficacy and mechanisms of MNE in ameliorating alcohol-induced liver injury.

Metabolic Obesity Phenotypes and Incident Cardiovascular Outcomes in Middle-Aged and Older Korean Adults: A Longitudinal 10-Year Analysis of the Korean Genome and Epidemiology Study.

Background: This study investigated the association of four metabolic obesity phenotypes with incident coronary artery disease and stroke in a large-scale, community population-based, prospective Korean cohort observed for over 10 years. Methods: The study participants included 7374 adults aged 40-69 years, drawn from the Korean Genome and Epidemiology Study. Participants with different metabolic obesity phenotypes were categorized according to body weight and metabolic health status into four groups: metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy nonobese (MUHNO), and metabolically unhealthy obese (MUHO). Combined cardiovascular events were defined as coronary artery disease and stroke. We used multivariate Cox proportional hazards regression models to prospectively assess hazard ratios (HRs) with 95% confidence intervals (CIs) for incident coronary artery disease or stroke over 10 years after the baseline survey. Results: During the follow-up period, newly developed coronary artery disease, stroke, and combined cardiovascular events were diagnosed in 151 (2.0%), 137 (1.9%), and 283 (3.8%) participants, respectively. After adjusting for confounding variables, the HRs (95% CIs) for incident combined cardiovascular events were 1.81 (1.34-2.46) in the MUHO group, 1.29 (0.92-1.81) in the MUHNO group, and 1.21 (0.81-1.79) in the MHO group compared with those in the MHNO group. Conclusions: This study revealed distinct risks associated with four metabolic obesity phenotypes concerning incident coronary artery disease and stroke. After adjusting for potential confounding variables, the results indicated that MUHO, but not MUHNO or MHO, showed a higher risk of developing coronary artery disease and stroke than MHNO.

Using propensity score matching analysis to compare between cardiometabolic risk factors and physical activity type in Korean adults: findings from a nationwide population-based survey.

PURPOSE: We aimed to assess the effects of different exercise modalities on cardiometabolic risk factors within a comprehensive, representative sample of the Korean population. METHODS: We categorized 13,971 adult participants into aerobic exercise (AE), resistance exercise (RE), combined aerobic and resistance exercise (TE), insufficient exercise, and inactive groups. Multivariable regressions were conducted to compare the incidence of chronic diseases across the groups before and after propensity score matching (PSM). RESULTS: The TE and RE groups had significantly lower waist circumference (WC), mean blood pressure (BP), glucose and insulin-related indices, and white blood cell count (WBC) measures, with TE showing the most significant differences. The TE group had significantly lower triglyceride levels and higher high-density lipoprotein-cholesterol levels. Post-PSM, the TE group had the lowest risk for metabolic syndrome, hypertension, and diabetes, closely followed by the RE group when compared with the inactive group. In a subgroup analysis, RE consistently exhibited benefits including lower body mass index, WC, BP, total cholesterol, glucose and insulin-related indices, and WBC count when compared with AE. RE may be associated with reduced incidence of cardiometabolic diseases compared to AE alone. CONCLUSION: TE appears to be associated with significant reduction in cardiometabolic risk in Korean adults. RE possibly provides a more favorable cardiometabolic effect than AE.

Isoegomaketone exhibits potential as a new Mycobacterium abscessus inhibitor.

Although the incidence of Mycobacterium abscessus infection has recently increased significantly, treatment is difficult because this bacterium is resistant to most anti-tuberculosis drugs. In particular, M. abscessus is often resistant to available macrolide antibiotics, so therapeutic options are extremely limited. Hence, there is a pressing demand to create effective drugs or therapeutic regimens for M. abscessus infections. The aim of the investigation was to assess the capability of isoegomaketone (iEMK) as a therapeutic option for treating M. abscessus infections. We determined the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of iEMK for both reference and clinically isolated M. abscessus strains. In addition to time-kill and biofilm formation assays, we evaluated iEMK's capability to inhibit M. abscessus growth in macrophages using an intracellular colony counting assay. iEMK inhibited the growth of reference and clinically isolated M. abscessus strains in macrophages and demonstrated effectiveness at lower concentrations against macrophage-infected M. abscessus than when used to treat the bacteria directly. Importantly, iEMK also exhibited anti-biofilm properties and the potential to mitigate macrolide-inducible resistance, underscoring its promise as a standalone or adjunctive therapeutic agent. Overall, our results suggest that further development of iEMK as a clinical drug candidate is promising for inhibiting M. abscessus growth, especially considering its dual action against both planktonic bacteria and biofilms.

Difference in association of carbohydrate intake with all-cause mortality between middle-aged and older Korean adults with and without diabetes mellitus: A prospective study.

BACKGROUND & AIMS: The relationship between diet and health, particularly the role of carbohydrates, has been extensively studied. However, carbohydrate intake based on individual health conditions remains unclear. Here, we aimed to investigate whether the association between carbohydrate intake and all-cause mortality varied between individuals with and without diabetes mellitus (DM). METHODS: This prospective cohort study used data from the Korean Genome and Epidemiology Study (KoGES). Overall, 143,050 participants were included, with 10.1% having DM. Dietary intake was assessed using a semiquantitative food frequency questionnaire. Cox proportional hazards regression models were used to assess the association between carbohydrate intake and mortality after adjusting for confounders. RESULTS: The study showed that 5436 deaths occurred during the median follow-up period of 10.1 years. A significant interaction between carbohydrate intake and DM was observed in the study population (interaction p = 0.061). Higher carbohydrate intake proportion was associated with an increased risk of all-cause mortality among individuals with DM (adjusted hazard ratio [HR], p-value = 1.10 [1.01-1.20], p = 0.032). Conversely, no association was observed between the proportion of carbohydrate intake and all-cause mortality in participants without DM. Additionally, both total sugar and added sugar intakes were associated with an increased risk of all-cause mortality in participants with DM (adjusted HR, p-value = 1.02 [1.01-1.04], p < 0.001 and 1.18 [1.13-1.24], p < 0.001). CONCLUSIONS: High carbohydrate (%) and added sugar intake were associated with an increased mortality risk in individuals with DM. Reducing carbohydrate intake and opting for healthy carbohydrates to mitigate mortality risk may be beneficial for individuals with DM, particularly when compared with the general population.

Sarcopenia with decreased total psoas muscle area in children with high-risk neuroblastoma.

BACKGROUND: We calculated psoas muscle area (PMA) z-scores in high-risk neuroblastoma patients undergoing treatment to examine the clinical significance of sarcopenia in this cohort. METHODS: We analyzed retrospective data from patients aged 0-18 who were diagnosed with abdominal neuroblastoma between 2005 and 2019 at Samsung Medical Center. Patients categorized as high-risk undergone induction chemotherapy, neuroblastoma excision, and tandem high-dose chemotherapy with autologous stem cell transplantation (HDCT/auto-SCT) were selected. L3-4 lumbar levels on axial CT images were identified and we measured the areas of the left and right psoas muscles to determine tPMA. Total PMA z-scores were calculated using an open online tool. RESULTS: There were 45 boys and 25 girls with a mean age of 3.86 years. CT images taken at initial diagnosis and after tandem HDCT/auto-SCT were selected to calculate tPMA z-scores. Mean elapsed time between the two measurements was 12.91 ± 1.73 months. Mean tPMA z-score significantly decreased from -0.21 ± 1.29 to -0.66 ± 0.97 (p = 0.022). Length of hospital stay was significantly longer in the group of patients whose tPMA z-scores decreased by more than .45 (177.62 ± 28.82 days vs. 165.75 ± 21.34 days, p = 0.049). Presence of sarcopenia at initial diagnosis was a significant risk factor for bacterial infection during neuroblastoma treatment. CONCLUSION: tPMA z-scores in high-risk neuroblastoma patients decreased significantly following a treatment regimen that included induction chemotherapy, tumor resection surgery, and HDCT/auto-SCT. A greater decrease in tPMA z-score was associated with longer hospital stay during treatment.

Non-Insulin-Based Indices of Insulin Resistance for Predicting Incident Albuminuria: A Nationwide Population-Based Study.

Background: Studies have shown that incident albuminuria is associated with insulin resistance (IR); however, an IR marker that best predicts the prevalence of albuminuria has not yet been established. This study explored the association between IR and incident albuminuria using various IR indices, including the homeostasis model assessment of IR (HOMA-IR), metabolic score for IR (METS-IR), and triglyceride-glucose (TyG) index, and compared their predictive abilities for the prevalence of albuminuria. Methods: A total of 4,982 Korean adults from the 2019 Korea National Health and Nutritional Examination Survey were analyzed. The odds of albuminuria were determined using the quartiles of the IR indices. Receiver operating characteristic (ROC) curves were used to calculate the area under the ROC curve and predictability. The cutoff values for albuminuria detection were also computed. Results: An increase in the quartiles of all three IR indices was associated with incident albuminuria, even after full adjustment for covariates (HOMA-IR: odds ratio [OR], 1.906; 95% confidence interval [CI], 1.311-2.772; P=0.006; METS-IR: OR, 2.236; 95% CI, 1.353-3.694; P=0.002; TyG index: OR, 1.757; 95% CI, 1.213-2.544; P=0.003). The area under the ROC curve for incident albuminuria based on the HOMA-IR, METS-IR, and TyG indices was 0.594 (95% CI, 0.568-0.619), 0.633 (95% CI, 0.607-0.659), and 0.631 (95% CI, 0.606-0.656), respectively. The optimal cutoff values for predicting albuminuria were 2.38, 35.38, and 8.72 for the HOMA-IR, METS-IR, and TyG indices, respectively. Conclusion: The METS-IR and TyG indices outperformed HOMA-IR in predicting incident albuminuria.

Secular trends in dietary energy, carbohydrate, fat, and protein intake among Korean adults, 2010-2020 KHANES.

OBJECTIVES: The composition and balance of macronutrient intake play key roles in promoting a longer lifespan. In this study, we aimed to investigate the secular trends in carbohydrate, fat, and protein intakes in South Koreans from 2010 to 2020. METHODS: We examined the dietary nutritional intake of South Koreans using data from the Korean National Health and Nutrition Examination Survey. A total of 60,190 adults aged ≥19 y who completed the 24-h dietary recall interviews in a single day on all survey periods were included in this study. The outcomes included changes in macronutrient intake according to subgroups, such as age; sex; and the presence of diabetes, dyslipidemia, stroke, or heart disease, as well as energy intake from macronutrients. RESULTS: The study population showed a significant decrease in total energy intake from 2010 to 2020, with a corresponding decrease in the percentage of energy intake from carbohydrates (p-values for trend < 0.001). Conversely, the proportions of energy intake from proteins and fats increased during the same period (p < 0.001). Subgroup analyses revealed variations in macronutrient intake trends according to age, sex, obesity status, and underlying diseases. The analysis of trends in energy intake from various fat subtypes, total sugar, and fiber revealed a decrease in the energy intake percentage of total sugar from 2016 to 2020 and an increase in the energy intake percentage of all fat subtypes and fiber from 2013 to 2020. CONCLUSIONS: In the past 10 y, the dietary patterns in Korea have shifted toward the consumption of high-fat and high-protein diets with reduced carbohydrate intake.

Topical minoxidil and dietary supplement for the treatment of chemotherapy-induced alopecia in childhood: a retrospective cohort study.

Chemotherapy-induced alopecia (CIA) is a common and debilitating condition in children, with limited research on its characteristics and treatment. Therefore, this study aims to describe the characteristics of pediatric patients with CIA and the treatment outcomes of topical minoxidil and L-cystine, medicinal yeast, and pantothenic acid complex-based dietary supplements (CYP). This retrospective cohort study analyzed data from patients who underwent high-dose conditioning chemotherapy followed by hematopoietic stem cell transplantation and were treated with either topical minoxidil or CYP for CIA between January 2011 and January 2022. Among the 70 patients evaluated, 61 (87.1%) experienced clinical improvement. Patients in the groups with superior treatment outcomes received a greater cumulative amount of minoxidil and underwent treatment for a more extended duration (P < 0.05) than those in the other groups. All 70 (100%) patients received topical minoxidil, and 42 (60%) were administered CYP. Hair thickness was significantly higher in the combination therapy group than in the minoxidil monotherapy group (21.4% vs. 9.3%, P = 0.02). However, only 3 (4.3%) patients reported mild and self-limiting adverse events. In conclusion, our study shows that minoxidil and CYP administration represent viable treatment options for pediatric CIA.

Co-treatment with melatonin and ortho-topolin riboside reduces cell viability by altering metabolic profiles in non-small cell lung cancer cells.

Lung cancer is a highly prevalent and lethal malignancy worldwide, with non-small cell lung cancer (NSCLC) accounting for 85% of cancer-related deaths. In this study, the effects of co-treatment with melatonin and ortho-topolin riboside (oTR) on the cell viability and alteration of metabolites and transcripts were investigated in NSCLC cells using gas chromatography-mass spectrometry (GC-MS) and next-generation sequencing (NGS). The co-treatment of melatonin and oTR exhibited synergistic effects on the reduction of cell viability and alteration of metabolic and transcriptomic profiles in NSCLC cells. We observed that the co-treatment inhibited glycolytic function and mitochondria respiration, and downregulated glycine, serine and threonine metabolism alongside tyrosine metabolism in NSCLC cells. In the glycine, serine and threonine metabolism pathway, the co-treatment resulted in a significant 8.4-fold reduction in the expression level of the SDS gene, which encodes the enzyme responsible for the breakdown of serine to pyruvate. Moreover, co-treatment decreased the gene expression of TH, DDC, and CYP1A1 in tyrosine metabolism. Additionally, we observed that the co-treatment resulted in a significant 146.9-fold reduction in the expression of the DISC1 gene. The alteration in metabolites and transcript expressions might provide information to explain the cytotoxicity of co-treatment of melatonin and oTR in NSCLC cells. Our study presents insights into the synergistic anticancer effect of the co-treatment of melatonin and oTR, which could be a potential future therapeutic strategy for the treatment of NSCLC patients.

Estimation of Validity of A-Mode Ultrasound for Measurements of Muscle Thickness and Muscle Quality.

This study aimed to determine whether amplitude modulation (A-mode) ultrasound (US) provides accurate and reliable measurements comparable to those obtained using brightness modulation (B-mode) US under diverse conditions. Thirty healthy participants (15 women and 15 men) underwent measurements of subcutaneous fat thickness (SFT), muscle thickness (MT), and muscle quality (MQ) in the trapezius and biceps brachii muscles using both US modes before and after exercises designed to stimulate the respective muscles. Among the three key indices, the results demonstrated the high validity of the A-mode, with minimal mean differences (MDs) between the two devices less than 0.91 mm and intra-class correlation coefficients (ICCs) exceeding 0.95 for all measures. In addition, the correlation coefficients between the error scores and average scores for the trapezius and biceps brachii suggested no evidence of systematic error. The trapezius MT and MQ significantly increased, and the biceps brachii MT significantly increased after the exercises (p < 0.05). Notably, both the A- and B-modes exhibited the same trend in these post-exercise changes in the muscle. This study suggests that low-cost and low-resolution A-mode US provides measurements of SFT, MT, and MQ similar to the more expensive, high-resolution B-mode imaging. A-mode US is an affordable and portable alternative for muscle assessment.

Mature microRNA-binding protein QKI promotes microRNA-mediated gene silencing.

Although Argonaute (AGO) proteins have been the focus of microRNA (miRNA) studies, we observed AGO-free mature miRNAs directly interacting with RNA-binding proteins, implying the sophisticated nature of fine-tuning gene regulation by miRNAs. To investigate microRNA-binding proteins (miRBPs) globally, we analyzed PAR-CLIP data sets to identify RBP quaking (QKI) as a novel miRBP for let-7b. Potential existence of AGO-free miRNAs were further verified by measuring miRNA levels in genetically engineered AGO-depleted human and mouse cells. We have shown that QKI regulates miRNA-mediated gene silencing at multiple steps, and collectively serves as an auxiliary factor empowering AGO2/let-7b-mediated gene silencing. Depletion of QKI decreases interaction of AGO2 with let-7b and target mRNA, consequently controlling target mRNA decay. This finding indicates that QKI is a complementary factor in miRNA-mediated mRNA decay. QKI, however, also suppresses the dissociation of let-7b from AGO2, and slows the assembly of AGO2/miRNA/target mRNA complexes at the single-molecule level. We also revealed that QKI overexpression suppresses cMYC expression at post-transcriptional level, and decreases proliferation and migration of HeLa cells, demonstrating that QKI is a tumour suppressor gene by in part augmenting let-7b activity. Our data show that QKI is a new type of RBP implicated in the versatile regulation of miRNA-mediated gene silencing.

Novel Lipid Nanoparticles Stable and Efficient for mRNA Transfection to Antigen-Presenting Cells.

mRNA vaccines have emerged as a pivotal tool in combating COVID-19, offering an advanced approach to immunization. A key challenge with these vaccines is their need for extremely-low-temperature storage, which affects their stability and shelf life. Our research addresses this issue by enhancing the stability of mRNA vaccines through a novel cationic lipid, O,O'-dimyristyl-N-lysyl aspartate (DMKD). DMKD effectively binds with mRNA, improving vaccine stability. We also integrated phosphatidylserine (PS) into the formulation to boost immune response by promoting the uptake of these nanoparticles by immune cells. Our findings reveal that DMKD-PS nanoparticles maintain structural integrity under long-term refrigeration and effectively protect mRNA. When tested, these nanoparticles containing green fluorescent protein (GFP) mRNA outperformed other commercial lipid nanoparticles in protein expression, both in immune cells (RAW 264.7 mouse macrophage) and non-immune cells (CT26 mouse colorectal carcinoma cells). Importantly, in vivo studies show that DMKD-PS nanoparticles are safely eliminated from the body within 48 h. The results suggest that DMKD-PS nanoparticles present a promising alternative for mRNA vaccine delivery, enhancing both the stability and effectiveness of these vaccines.

Importance of dialysis specialists in early mortality in elderly hemodialysis patients: a multicenter retrospective cohort study.

The early mortality rate in elderly patients undergoing hemodialysis is more than twice that in young patients, requiring more specialized healthcare. We investigated whether the number of professional dialysis specialists affected early mortality in elderly patients undergoing hemodialysis. This multicenter retrospective cohort study analyzed data from 1860 patients aged ≥ 70 years who started hemodialysis between January 2010 and December 2017. Study regions included Seoul, Gyeonggi-do, Gangwon-do, Daejeon/Chungcheong-do, Daegu/Gyeongsangbuk-do, and Busan/Ulsan/Gyeongsangnam-do. The number of patients undergoing hemodialysis per dialysis specialist was calculated using registered data from each hemodialysis center. Early mortality was defined as death within 6 months of hemodialysis initiation. Gangwon-do (28.3%) and Seoul (14.5%) showed the highest and lowest early mortality rate, respectively. Similarly, Gangwon-do (64.6) and Seoul (43.9) had the highest and lowest number of patients per dialysis specialist, respectively. Relatively consistent results were observed for the regional rankings of early mortality rate and number of patients per dialysis specialist. Multivariate Cox regression analysis-adjusted for previously known significant risk factors-revealed that the number of patients per dialysis specialist was an independent risk factor for early mortality (hazard ratio: 1.031, p < 0.001). This study underscores the growing need for dialysis specialists for elderly hemodialysis patients in Korea.