Background/Aims: Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression and complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent gut microbiota and metabolic signatures in patients with liver cirrhosis. Methods: Microbiome taxonomic profiling was performed on 194 stool samples (52 controls and 142 cirrhosis patients) via V3-V4 16S rRNA sequencing. Next, 51 samples (17 controls and 34 cirrhosis patients) were selected for fecal metabolite profiling via gas chromatography mass spectrometry and liquid chromatography coupled to timeof-flight mass spectrometry. Correlation analyses were performed targeting the gut-microbiota, metabolites, clinical parameters, and presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, and deceased). Results: Veillonella bacteria, Ruminococcus gnavus, and Streptococcus pneumoniae are cirrhosis-related microbiotas compared with control group. Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium, and Hungatella_uc were associated with complications in the cirrhosis group. The areas under the receiver operating characteristic curve (AUROCs) for the diagnosis of cirrhosis, encephalopathy, hepatorenal syndrome, and deceased were 0.863, 0.733, 0.71, and 0.69, respectively. The AUROCs of mixed microbial species for the diagnosis of cirrhosis and complication were 0.808 and 0.847, respectively. According to the metabolic profile, 5 increased fecal metabolites in patients with cirrhosis were biomarkers (AUROC >0.880) for the diagnosis of cirrhosis and complications. Clinical markers were significantly correlated with the gut microbiota and metabolites. Conclusions Cirrhosis-dependent gut microbiota and metabolites present unique signatures that can be used as noninvasive biomarkers for the diagnosis of cirrhosis and its complications.

The biogenesis and biological roles of extracellular vesicles (EVs) in the progression of liver diseases have attracted considerable attention in recent years. EVs are membrane-bound nanosized vesicles found in different types of body fluids and contain various bioactive materials, including proteins, lipids, nucleic acids, and mitochondrial DNA. Based on their origin and biogenesis, EVs can be classified as apoptotic bodies, microvesicles, and exosomes. Among these, exosomes are the smallest EVs (30-150 nm in diameter), which play a significant role in cell-to-cell communication and epigenetic regulation. Moreover, exosomal content analysis can reveal the functional state of the parental cell. Therefore, exosomes can be applied to various purposes, including disease diagnosis and treatment, drug delivery, cell-free vaccines, and regenerative medicine. However, exosome-related research faces two major limitations: isolation of exosomes with high yield and purity and distinction of exosomes from other EVs (especially microvesicles). No standardized exosome isolation method has been established to date; however, various exosome isolation strategies have been proposed to investigate their biological roles. Exosome-mediated intercellular communications are known to be involved in alcoholic liver disease and nonalcoholic fatty liver disease development. Damaged hepatocytes or nonparenchymal cells release large numbers of exosomes that promote the progression of inflammation and fibrogenesis through interactions with neighboring cells. Exosomes are expected to provide insight on the progression of liver disease. Here, we review the biogenesis of exosomes, exosome isolation techniques, and biological roles of exosomes in alcoholic liver disease and nonalcoholic fatty liver disease.

Purpose: This study evaluates the radiation shielding performance of a new lead-free tungsten-based sheet to reduce the radiation exposure of operators and patients under C-arm fluoroscopy. Materials and Methods: A non-lead radiation shielding sheet (ROO201128; Pentas, Korea) was fabri-cated using tungsten and bismuth. The dose measurements were conducted using a C-arm fluoroscopy machine at 64 kVp and 1.5 mA, assuming two possible scenarios according to the position of the sheet. In each scenario, measurements were conducted at three distances (30, 60, and 90 cm) away from the beam center and in three directions (cephal, caudal, and operator’s direction). Results: In the area within a radius of 60 cm from the beam center, the measured doses were reduced by 66.3% on mean, and the doses measured at distances more than 60 cm were less than 0.1 mSv/h in both scenarios. The most beneficial utilization of the lead-free shielding sheet was verified during C-arm fluoroscopy by placing the sheet on the X-ray tube. The operator’s radiation exposure was reduced by 56.6% when the sheet was placed under the phantom, and by 81.0% when the sheet was placed on the X-ray tube. Conclusion The use of lead-free radiation shielding sheets under C-arm fluoroscopy was effective in reducing radiation exposure, and the most beneficial scenario in which the sheet can be utilized was verified when the sheet was placed on the X-ray tube.

Background: To evaluate the chemosensitivity to doxorubicin (DOX) in two primary cells derived from a tumor of FVB/N-Trp53tm1Hw1 knockout (KO) mice with TALEN-mediated Trp53 mutant gene, we evaluated the cell survivability, cell cycle distribution, apoptotic cell numbers and apoptotic protein expression in solid tumor cells and ascetic tumor cells treated with DOX. Results: The primary tumor cells showed a significant (P < 0.05) defect for UV-induced upregulation of the Trp53 pro-tein, and consisted of different ratios of leukocytes, fibroblasts, epithelial cells and mesenchymal cells. The ­ IC50 level to DOX was lower in both primary cells ­(IC50 = 0.12 μM and 0.20 μM) as compared to the CT26 cells ­(IC50 = 0.32  μM), although the solid tumor was more sensitive. Also, the number of cells arrested at the G0/G1 stage was significantly decreased (24.7–23.1% in primary tumor cells treated with DOX, P < 0.05) while arrest at the G2 stage was enhanced to 296.8–254.3% in DOX-treated primary tumor cells compared with DOX-treated CT26 cells. Furthermore, apoptotic cells of early and late stage were greatly increased in the two primary cell-lines treated with DOX when compared to same conditions for CT26 cells. However, the Bax/Bcl-2 expression level was maintained constant in the primary tumor and CT26 cells. Conclusions To the best of our knowledge, these results are the first to successfully detect an alteration in chemosensitivity to DOX in solid tumor cells and ascetic tumor cells derived from tumor of FVB/N-Trp53tm1Hw1 mice TALENmediated Trp53 mutant gene.

Purpose: Phosphorylated AKT1 (p-AKT1) at Ser473 is a functional isoform of AKT and a key component of the PI3K/mTOR/AKT pathway. This study aimed to evaluate the prognostic significance of p-AKT1 (Ser473) based on the molecular subtypes of breast cancer. Methods: To investigate the prognostic value of p-AKT1 (Ser473), we performed a retrospective chart review of patients with breast cancer. Data on p-AKT1 (Ser473) positivity, hormone receptor (HR) status, human epidermal growth factor receptor 2 (HER2) expression status, and other clinicopathological factors were obtained. Furthermore, the therapeutic effect of blocking p-AKT1 (Ser473) in breast cancer cells was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell apoptosis assay, apoptosis protein array, and western blot analysis. Results: A total of 3,044 patients were evaluated, and the median follow-up time was 43 (range: 0–125) months. In patients with HR-positive and HER2-positive disease, the p-AKT1 (Ser473)-positive group had worse disease-free survival (DFS) than the p-AKT1 (Ser473)-negative group (hazard ratio, 1.9; 95% confidence interval, 1.1–3.5; p = 0.024). In the multivariate analysis, p-AKT1 (Ser473) remained a significantly worse prognostic factor in patients with HR-positive/HER2-positive breast cancer (p = 0.03). There was no difference in DFS according to p-AKT1 (Ser473) status among patients with other breast cancer subgroups.In vitro analysis showed that blocking p-AKT1 (Ser473) levels enhanced trastuzumab-induced cell death in HR-positive/HER2-positive and p-AKT1 (Ser473)-positive breast cancer cells. Conclusion p-AKT1 (Ser473) is a prognostic marker for poor outcomes in patients with HRpositive/HER2-positive breast cancer and may have a potential value as a therapeutic target.

Alpha-lipoic acid (ALA) is a naturally occurring antioxidant and has been previously used to treat diabetes and cardiovascular disease. However, the autophagy effects of ALA against oxidative stress-induced dopaminergic neuronal cell injury remain unclear. The aim of this study was to investigate the role of ALA in autophagy and apoptosis against oxidative stress in the SH-SY5Y human dopaminergic neuronal cell line. We examined SH-SY5Y phenotypes using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay (cell viability/proliferation), 4′,6-diamidino-2-phenylindole dihydrochloride nuclear staining, Live/Dead cell assay, cellular reactive oxygen species (ROS) assay, immunoblotting, and immunocytochemistry. Our data showed ALA attenuated hydrogen peroxide (H2O2)-induced ROS generation and cell death. ALA effectively suppressed Bax up-regulation and Bcl-2 and BclxL down-regulation. Furthermore, ALA increased the expression of the antioxidant enzyme, heme oxygenase-1. Moreover, the expression of Beclin-1 and LC-3 autophagy biomarkers was decreased by ALA in our cell model. Combined, these data suggest ALA protects human dopaminergic neuronal cells against H2O2-induced cell injury by inhibiting autophagy and apoptosis.

Alpha-lipoic acid (ALA) is a naturally occurring antioxidant and has been previously used to treat diabetes and cardiovascular disease. However, the autophagy effects of ALA against oxidative stress-induced dopaminergic neuronal cell injury remain unclear. The aim of this study was to investigate the role of ALA in autophagy and apoptosis against oxidative stress in the SH-SY5Y human dopaminergic neuronal cell line. We examined SH-SY5Y phenotypes using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay (cell viability/proliferation), 4′,6-diamidino-2-phenylindole dihydrochloride nuclear staining, Live/Dead cell assay, cellular reactive oxygen species (ROS) assay, immunoblotting, and immunocytochemistry. Our data showed ALA attenuated hydrogen peroxide (H2O2)-induced ROS generation and cell death. ALA effectively suppressed Bax up-regulation and Bcl-2 and BclxL down-regulation. Furthermore, ALA increased the expression of the antioxidant enzyme, heme oxygenase-1. Moreover, the expression of Beclin-1 and LC-3 autophagy biomarkers was decreased by ALA in our cell model. Combined, these data suggest ALA protects human dopaminergic neuronal cells against H2O2-induced cell injury by inhibiting autophagy and apoptosis.

BACKGROUND: The 48/6 Model of Care is an integrative care initiative for improving the health outcomes of hospitalized older patients; however, its applicability in community-dwelling older adults as a health screening tool has not been investigated. The present study aimed to examine the applicability of this model, prevalence of dysfunction in 6 care areas, and its relationship with self-reported mobility in community-dwelling older adults.METHODS: This was a cross-sectional survey study of community-dwelling adults aged 65 or older. Participants were screened for problems using 9 items corresponding to the 6 care areas of the 48/6 Model of Care (cognitive functioning, functional mobility, pain management, nutrition and hydration, bladder and bowel management, and medication management). Mobility was assessed via the Life-Space Assessment (LSA). We examined the correlation between each screening item and the LSA.RESULTS: A total of 444 older adults (260 women, 58.6%) participated. The mean number of health problems was 2.3 ± 2.1, with the most common being pain, cognitive impairment, and urinary incontinence. These problems and LSA scores were significantly different by age groups. A multiple regression analysis showed that polypharmacy (β = −10.567, P < 0.001), dysphagia (β = −9.610, P = 0.021), and pain (β = −7.369, P = 0.004) were significantly associated with life-space mobility after controlling for age.CONCLUSION: The 48/6 Model of Care is applicable to community-dwelling older adults, who show high prevalence of dysfunction in the 6 care areas. This study supports the role of the model in screening for the health status of older adults living in the community, and in estimating mobility.
Adult ; Cognition Disorders ; Cross-Sectional Studies ; Deglutition Disorders ; Female ; Humans ; Mass Screening ; Pain Management ; Polypharmacy ; Prevalence ; Urinary Bladder ; Urinary Incontinence

BACKGROUND: The 48/6 Model of Care is an integrative care initiative for improving the health outcomes of hospitalized older patients; however, its applicability in community-dwelling older adults as a health screening tool has not been investigated. The present study aimed to examine the applicability of this model, prevalence of dysfunction in 6 care areas, and its relationship with self-reported mobility in community-dwelling older adults. METHODS: This was a cross-sectional survey study of community-dwelling adults aged 65 or older. Participants were screened for problems using 9 items corresponding to the 6 care areas of the 48/6 Model of Care (cognitive functioning, functional mobility, pain management, nutrition and hydration, bladder and bowel management, and medication management). Mobility was assessed via the Life-Space Assessment (LSA). We examined the correlation between each screening item and the LSA. RESULTS: A total of 444 older adults (260 women, 58.6%) participated. The mean number of health problems was 2.3 ± 2.1, with the most common being pain, cognitive impairment, and urinary incontinence. These problems and LSA scores were significantly different by age groups. A multiple regression analysis showed that polypharmacy (β = −10.567, P < 0.001), dysphagia (β = −9.610, P = 0.021), and pain (β = −7.369, P = 0.004) were significantly associated with life-space mobility after controlling for age. CONCLUSION The 48/6 Model of Care is applicable to community-dwelling older adults, who show high prevalence of dysfunction in the 6 care areas. This study supports the role of the model in screening for the health status of older adults living in the community, and in estimating mobility.

PURPOSE: This study aimed to investigate the current statistics of professional medical support staffs(PMSSs) working in general hospitals with less than 500 beds. METHODS: This study was conducted on 35 general hospitals with less than 500 beds from September 11th to October 27th, 2017. RESULTS: Four hundred fifty one PMSSs were currently providing medical support. The number of clinical nurse experts was the highest among the roles, followed by Physician Assistants(PA) and Advanced Practice Nurses. The mean job satisfaction score was 3.07 out of 5. In the case of PA group, most of the delegated prescriptions were performed, however the delegated roles were not much documented in written format. The paucity of documentation requires a development of a committee for PMSSs, including a development of selection criteria and a scope of practice in each institution. CONCLUSION: The results of this study suggested the composition of a committee for PMSSs in the medical institutions and renaming the specified titles of PMSSs.
Hospitals, General ; Humans ; Job Satisfaction ; Nurse Clinicians ; Nurse Practitioners ; Nursing ; Patient Selection ; Physician Assistants ; Prescriptions