Cholestatic liver diseases can progress to end-stage liver disease and reduce patients’ quality of life. Although their underlying mechanisms are still incompletely elucidated, oxidative stress is ...considered to be a key contributor to these diseases. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that displays antioxidant action. It has been found that this enzyme plays a protective role against various inflammatory diseases. However, the role of HO-1 in cholestatic liver diseases has not yet been investigated. Here, we examined whether pharmacological induction of HO-1 by cobalt protoporphyrin (CoPP) ameliorates cholestatic liver injury. To this end, a murine model of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet feeding was used. Administration of CoPP ameliorated liver damage and cholestasis with HO-1 upregulation in DDC diet-fed mice. Induction of HO-1 by CoPP suppressed the DDC diet-induced oxidative stress and hepatocyte apoptosis. In addition, CoPP attenuated cytokine production and inflammatory cell infiltration. Furthermore, deposition of the extracellular matrix and expression of fibrosis-related genes after DDC feeding were also decreased by CoPP. HO-1 induction decreased the number of myofibroblasts and inhibited the transforming growth factor-β pathway. Altogether, these data suggest that the pharmacological induction of HO-1 ameliorates cholestatic liver disease by suppressing oxidative stress, hepatocyte apoptosis, and inflammation.
Ginseng (Panax ginseng C.A. Meyer) is one of the most popular medicinal herbs and contains pharmacologically active components, ginsenosides, in its roots. Ginsenosides, a class of tetracyclic ...triterpene saponins, are thought to be synthesized from dammarenediol-II after hydroxylation by the Cyt P450 (CYP) enzyme and then glycosylation by glycosyltransferase (GT). However, no genes encoding the hydroxylation and glycosylation in ginsenoside biosynthesis have been identified. Here, we identify protopanaxadiol synthase, which is a CYP enzyme (CYP716A47), to be involved in the hydroxylation of dammarenediol-II at the C-12 position to yield protopanaxadiol. Nine putative full CYP sequences were isolated from the expressed sequence tags (ESTs) of methyl jasmonate (MeJA)-treated adventitious ginseng roots. The CYP716A47 gene product was selected as the putative protopanaxadiol synthase because this gene was transcriptionally activated not only by MeJA treatment but also in transgenic ginseng that overexpresses squalene synthase and overproduces ginsenosides. In vitro enzymatic activity assays revealed that CYP716A47 catalyzed the oxidation of dammarenediol-II to produce protopanaxadiol. Ectopic expression of CYP716A47 in recombinant WAT21 yeasts that were fed dammarenediol-II yielded protopanaxadiol. Furthermore, co-expression of the dammarenediol synthase gene (PgDDS) and CYP716A47 in yeast yielded protopanaxadiol without adding dammarenediol-II. The chemical structures of the protopanaxadiol products from dammarenediol-II were confirmed using liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (LC/APCIMS). Thus, CYP716A47 is a dammarenediol 12-hydroxylase that produces protopanaxadiol from dammarenediol-II.
Medium cut-off (MCO) dialyzers help remove larger middle molecules associated with symptoms related to the accumulation of uremic retention solutes. We investigated the effect of an MCO dialyzer on ...the improvement of quality of life (QOL) in maintenance hemodialysis (HD) patients. Forty-nine HD patients with high-flux dialysis were randomly assigned to either an MCO (Theranova 400, Baxter) or a high-flux (FX CorDiax 80 or 60, Fresenius Medical Care) dialyzer and completed the study. QOL was assessed at baseline and after 12 weeks of treatment using the Kidney Disease Quality of Life Short Form-36, and pruritus was assessed using a questionnaire and visual analog scale. The reduction ratios of middle molecules were also evaluated. Laboratory markers, including serum albumin, did not differ between the two groups after 12 weeks. Removals of kappa and lambda free light chains were greater for MCO dialyzer than high-flux dialyzer. The MCO group had higher scores than the high-flux group in the domains of physical functioning and physical role (75.2 ± 20.8 vs. 59.8 ± 30.1, P = 0.042; 61.5 ± 37.6 vs. 39.0 ± 39.6, P = 0.047, respectively), and the MCO group had lower mean scores for morning pruritus distribution and the frequency of scratching during sleep (1.29 ± 0.46 vs. 1.64 ± 0.64, P = 0.034; 0.25 ± 0.53 vs. 1.00 ± 1.47, P = 0.023, respectively). MCO dialyzers may improve patient-reported outcomes, particularly the physical components of QOL and uremic pruritus, in patients with high-flux dialyzers.
The effect of Ag decoration on the gas sensing characteristics of SnO2 nanowire (NW) networks was investigated. The Ag layers with thicknesses of 5–50 nm were uniformly coated on the surface of SnO2 ...NWs via e-beam evaporation, which were converted into isolated or continuous configurations of Ag islands by heat treatment at 450 °C for 2 h. The SnO2 NWs decorated by isolated Ag nano-islands displayed a 3.7-fold enhancement in gas response to 100 ppm C2H5OH at 450 °C compared to pristine SnO2 NWs. In contrast, as the Ag decoration layers became continuous, the response to C2H5OH decreased significantly. The enhancement and deterioration of the C2H5OH sensing characteristics by the introduction of the Ag decoration layer were strongly governed by the morphological configurations of the Ag catalysts on SnO2 NWs and their sensitization mechanism.
This study aimed to classify distinct subgroups of people who use both smartphone and the internet based on addiction severity levels. Additionally, how the classified groups differed in terms of sex ...and psychosocial traits was examined.
A total of 448 university students (178 males and 270 females) in Korea participated. The participants were given a set of questionnaires examining the severity of their internet and smartphone addictions, their mood, their anxiety, and their personality. Latent class analysis and ANOVA (analysis of variance) were the statistical methods used.
Significant differences between males and females were found for most of the variables (all <0.05). Specifically, in terms of internet usage, males were more addicted than females (P<0.05); however, regarding smartphone, this pattern was reversed (P<0.001). Due to these observed differences, classifications of the subjects into subgroups based on internet and smartphone addiction were performed separately for each sex. Each sex showed clear patterns with the three-class model based on likelihood level of internet and smartphone addiction (P<0.001). A common trend for psychosocial trait factors was found for both sexes: anxiety levels and neurotic personality traits increased with addiction severity levels (all P<0.001). However, Lie dimension was inversely related to the addiction severity levels (all P<0.01).
Through the latent classification process, this study identified three distinct internet and smartphone user groups in each sex. Moreover, psychosocial traits that differed in terms of addiction severity levels were also examined. It is expected that these results should aid the understanding of traits of internet and smartphone addiction and facilitate further study in this field.
We analyzed the Korean National Health and Nutrition Examination Survey (KNHANES) database to determine the trends of hypertension treatment and control rate in Korea over the past 10 years. In ...addition, we tried to investigate the effect of chronic medical conditions on hypertension management. We investigated the hypertension prevalence, awareness, treatment, and control rate from 2008 to 2017. KNHANES, which uses a stratified multistage sampling design, is a cross-sectional, nationally representative survey conducted by the Korean government. A total of 59,282 adults (≥ 20 years) were included, which was representative of the total population of around 40 million Koreans per year. The mean age was 50.7 ± 16.4 years and 42.6% were male. The prevalence of hypertension, hypercholesterolemia, diabetes mellitus, and obesity significantly increased over the 10 years. During this period, the hypertension treatment and control rate significantly improved. Hypertension treatment rate was significantly lower in the younger age group compared to the older age group, but the control rate among the treated patients was not significantly different between age groups. The treatment and control rates of hypertension were higher in patients with multimorbidity, which implies that it has a favorable effect on the treatment and control of hypertension. Hypertension treatment and control rate have improved over the past 10 years. The higher treatment and control rate in patients with multimorbidity suggest that the more aggressive surveillance might be associated with the improvement of hypertension treatment and control rate in Korea.
Deep learning has been recently applied to various areas of artificial intelligence, where it has displayed excellent performance. However, many deep‐learning models are a black box, which makes it ...difficult to interpret the models and understand the predictions. Explainability is crucial for critical real‐world systems (in the fields such as defense, aerospace, and security). To solve this problem, the concept of explainable artificial intelligence has emerged. For image classification, various approaches have been proposed to visually explain the model's prediction. A typical approach is layer‐wise relevance propagation, which generates a heatmap, where each pixel value represents the contributions to the model's predictions. However, even advanced versions of layer‐wise relevance propagation (such as contrastive layer‐wise relevance propagation and softmax‐gradient layer‐wise relevance propagation) have some limitations. Here, selective layer‐wise relevance propagation, which generates a clearer heatmap than the existing methods by combining relevance‐based methods and gradient‐based methods is proposed. To evaluate the proposed method and verify its effectiveness, we conduct comparative experiments. Qualitative and quantitative results show that selective layer‐wise relevance propagation produces less noisy, class‐discriminative, and object‐preserving results. The proposed method can be used to improve the explainability of deep‐learning models in image classification.
•CGA based multidisciplinary intervention was reviewed for past 10 years and summarized.•Consensus of domains derived from articles was effective in older hospitalized people.•Subdomain performance ...improves general strategy knowledge for multidisciplinary teams.•Consensus among the articles is the cornerstone for further CGA based intervention.•Findings warrant in geriatric health sector, to ensure policies improve outcomes.•Emerging trend of CGA and intervention would be an extension of current research.
Comprehensive geriatric assessment (CGA) is a multidisciplinary diagnostic and treatment process to evaluate medical, psychosocial, and functional capability. It is useful to develop a coordinated and integrated plan for frail older patients. This study aimed to examine the current scope of CGA based multidisciplinary team interventions in acute care setting to improve the health outcomes for older adults.
We searched electronic databases: PubMed, Ovid, PsychINFO, Scopus, RISS and KoreaMed from 2011 to 2021. The selected articles were extracted by three reviewers and cross checked by the fourth reviewer to resolve any conflicts. Data were synthesized and analyzed descriptively and thematically. Articles are nested three themes: inpatient (IN), emergency room (ER) and oncology patient (ONCO).
Of the 1830 articles that were screened, 710 were potentially eligible. Finally, 26 articles were selected and categorized as IN (n=8), ER (n=7) and ONCO (n=11). Geriatricians and nurses participated in most of the multidisciplinary teams followed by other health professionals. The most effective primary outcomes were focused and retrieved across five domains, screening, prevention, treatment, quality of care, and rehabilitation. The subdomains are problem lists which is common and problematic among hospitalized older patients and retrieved from the most commonly used multidisciplinary interventions according to each domain.
CGA based multidimensional intervention (MDI) are likely to be an effective in care of older adults. There is remarkable paradigm shift required to improve better health outcomes for hospitalized older adults. It also suggests that there is a need to design the CGA based MDI to build a standardized protocol for older adults to maintain functional capacity and increase likelihood of living in their own home.
Display omitted
Background Allergic rhinitis (AR) and asthma are 2 entities of allergic airway diseases that frequently occur together, which is referred to as united airways . In contrast to this general concept, ...we hypothesized that innate immunity of the upper and lower airways is respectively distinctive, because the immunologic conditions of the nasal and lung mucosa as well as the functions of the immune cells within their epithelia are different. Objective We wanted to identify distinctive mechanisms of innate immunity in the nose and lung mucosa, which are responsible for house dust mite (HDM)–induced AR and allergic asthma (AA), respectively. Methods We constructed a mouse model of AR or AA induced by sensitization and consequent provocation with HDM extracts. Results HDM-derived β-glucans, rather than LPS, were proven to be essential to activating innate immunity in the nasal mucosa and triggering AR, which depended on Toll-like receptor 2 (TLR2), but not on TLR4; however, the LPS/TLR4 signaling axis, rather than β-glucans/TLR2, was critical to HDM-induced AA. These differences were attributed to the specific role of β-glucans and LPS in inducing the surface expression of TLR2 and TLR4 and their translocation to lipid rafts in nasal and bronchial epithelial cells, respectively. We also showed that dual oxidase 2–generated reactive oxygen species mediate both β-glucan–induced TLR2 activation and LPS-induced TLR4 activation. Conclusions We describe a novel finding of distinctive innate immunity of the nose and lungs, respectively, which trigger AR and AA, by showing the critical role of HDM-induced TLR activation via dual oxidase 2–mediated reactive oxygen species.
The fatigue, resistance, ambulation, illnesses, and loss of weight (FRAIL) scale is a screening tool for frailty status using a simple 5-item questionnaire. The aim of this study was to evaluate the ...clinical feasibility and validity of the Korean version of the FRAIL (K-FRAIL) scale.
Questionnaire items were translated and administered to 103 patients aged ≥ 65 years who underwent a comprehensive geriatric assessment at the Seoul National University Bundang Hospital. In this cross-sectional study, the K-FRAIL scale was compared with the domains and the multidimensional frailty index of the comprehensive geriatric assessment. We also assessed the time required to complete the scale.
The participants' mean age was 76.8 years (standard deviation SD, 6.1), and 55 (53.4%) were males. The mean overall frailty index was 0.19 (SD, 0.17). For K-FRAIL-robust, prefrail, and frail patients, the mean frailty indices were 0.09, 0.18, and 0.34, respectively (p for trend < 0.001). A higher degree of impairment in the K-FRAIL scale was associated with worse nutritional status, poor physical performance, functional dependence, and polypharmacy. The number of items with impairment in the K-FRAIL scale was positively associated with the frailty index (B = 3.73, p < 0.001). The K-FRAIL scale could differentiate vulnerability from robustness with a sensitivity of 0.90 and a specificity of 0.33. Of all patients, 75 (72.8%) completed the K-FRAIL scale within < 3 minutes.
The K-FRAIL scale is correlated with the frailty index and is a simple tool to screen for frailty in a clinical setting.
PDF
