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Glutamyl-prolyl-tRNA synthetase 1 (EPRS1) is known to associated with fibrosis through its catalytic activity to produce prolyl-tRNA. Although its catalytic inhibitor halofuginone (HF) has been known to inhibit the TGF-β pathway as well as to reduce prolyl-tRNA production for the control of fibrosis, the underlying mechanism how EPRS1 regulates the TGF-β pathway was not fully understood. Here, we show a noncatalytic function of EPRS1 in controlling the TGF-β pathway and hepatic stellate cell activation via its interaction with TGF-β receptor I (TβRI). Upon stimulation with TGF-β, EPRS1 is phosphorylated by TGF-β-activated kinase 1 (TAK1), leading to its dissociation from the multi-tRNA synthetase complex and subsequent binding with TβRI. This interaction increases the association of TβRI with SMAD2/3 while decreases that of TβRI with SMAD7. Accordingly, EPRS1 stabilizes TβRI by preventing the ubiquitin-mediated degradation of TβRI. HF disrupts the interaction between EPRS1 and TβRI, and reduces TβRI protein levels, leading to inhibition of the TGF-β pathway. In conclusion, this work suggests the novel function of EPRS1 involved in the development of fibrosis by regulating the TGF-β pathway and the antifibrotic effects of HF by controlling both of EPRS1 functions.

Byline: Saeyeon. Kim, Beatrice. Shih, In-Ae. Song, Tak. Oh PURPOSE: This study examined the risk factors of experiencing side effects from using intravenous patient-controlled analgesia (IV PCA) following lung and [...]

Purpose Worsening quality of life (QOL) is an important health issue in acute respiratory distress syndrome (ARDS) survivors. We aimed to investigate the prevalence of worsening QOL among ARDS survivors and their association with mortality. Methods South Korean National Health Insurance database information for all adults admitted to intensive care units for ARDS from January 1, 2010 to December 31, 2018 who survived [greater than or equal to] 365 days were included in this study. Results A total of 4452 ARDS survivors were included in the final analysis. Total QOL had worsened in 1667 (37.4%) of the survivors at the follow-up 1 year after being diagnosed with the syndrome. Specifically, 1298 patients (29.2%) experienced decreased income, 334 (7.5%) lost their jobs, and 327 (7.3%) had newly acquired disabilities. In the multivariable Cox regression analysis, worsening QOL was not associated with 2-year all-cause mortality among survivors (P = 0.140). However, newly acquired disability was associated with 1.74-fold (hazard ratio [HR]: 1.74, 95% confidence interval [CI] 1.31-2.33; P < 0.001) higher 2-year all-cause mortality, while decreased income (P = 0.571) and unemployment (P = 0.952) were not associated with it. In addition, newly acquired respiratory disability was associated with a 6.61-fold higher risk of 2-year respiratory mortality (HR: 6.61, 95% CI 3.14-13.90; P < 0.001). Conclusions At the 1-year follow-up period, one-third of ARDS survivors experienced worsening QOL in South Korea. Specifically, newly acquired disability was associated with a higher risk of 2-year all-cause and respiratory mortality among patients who survived ARDS., Author(s): Hey-ran Choi [sup.1], In-Ae Song [sup.2], Tak Kyu Oh [sup.2] [sup.3] Author Affiliations: (1) grid.411635.4, 0000 0004 0485 4871, Department of Anesthesiology and Pain Medicine, Inje University Seoul Paik [...]

Background: A careful approach is required when providing nutritional support to patients with acute respiratory distress syndrome (ARDS). This study investigated whether implementing a multidisciplinary nutritional support team (NST) is associated with improved survival outcomes in patients with ARDS. Methods: In a nationwide population‐based cohort study, all adult patients admitted to the intensive care unit (ICU) in South Korea with a primary diagnosis of ARDS from January 1, 2017, to December 31, 2021, were included. The NST comprised four professionals (physicians, full‐time nurses, full‐time pharmacists, and full‐time clinical dietitians). Patients admitted to ICUs with and without the NST system were allocated to the NST and non‐NST groups, respectively. Results: The analysis comprised a total of 15,555 patients with ARDS. Among them, 6615 (42.5%) were in the NST group, and 8940 (57.5%) were in the non‐NST group. After adjusting for covariates in the multivariable logistic regression, the NST group showed a 19% lower 30‐day mortality than the non‐NST group (odds ratio: 0.81, 95% confidence interval: 0.75–0.87, p <.001). Furthermore, after adjusting for covariates in multivariable Cox regression, the NST group showed a 12% lower 1‐year all‐cause mortality than the non‐NST group (hazard ratio: 0.88, 95% confidence interval: 0.85–0.92, p <.001). Conclusions: NST implementation was associated with enhanced 30‐day and 1‐year survival rates in patients with ARDS. These findings indicate that nutritional support provided by the NST may influence the survival outcomes of patients with ARDS in the ICU. [ABSTRACT FROM AUTHOR]

Recent information regarding the characteristics of people living with human immunodeficiency virus (HIV) (PLWH) is lacking. Therefore, we examined the incidence of HIV infection and epidemiologic characteristics of PLWH in South Korea using recent National Health Insurance Service database data. The HIV infection rate was 4.13 per 100,000 in 2017, 4.19 per 100,000 in 2018, 6.61 per 100,000 in 2019, 5.98 per 100,000 in 2020, 8.81 per 100,000 in 2021, and 4.14 per 100,000 in 2022. In 2016, the mean age of PLWH was 45.7 years (SD: 13.8 years), and it gradually increased to 49.0 years (standard deviation: 13.7 years) in 2022 over 7 years in South Korea. The proportion of male individuals among PLWH was 90.7% (19,970/22,026) in 2016, and it gradually increased to 92.3% (22,943/24,857) in 2022 over 7 years in South Korea. The proportion of anti-retroviral therapy (ART) users among PLWH in South Korea was 92.6% (20,388/22,026) in 2016, and it gradually increased to 97.9% (24,328/24,857) in 2022 over 7 years. In this population-based cohort analysis, we presented the HIV infection incidence and epidemiologic features of PLWH in South Korea. This study's results may influence future infection prevention strategies and policies for PLWH. [ABSTRACT FROM AUTHOR]

Background: Rapid response systems (RRSs) are used in hospitals to identify and treat deteriorating patients. However, RRS implementation and outcomes in orthopedic and surgical patients remain controversial. We aimed to investigate whether the RRS affects mortality and complications after orthopedic surgery. Methods: The National Health Insurance Service of South Korea provided the data for this population-based cohort study. Individuals who were admitted to the hospital that implemented RRS were categorized into the RRS group and those admitted to a hospital that did not implement the RRS were categorized into the non-RRS group. In-hospital mortality and postoperative complications were the endpoints. Results: A total of 931,774 adult patients were included. Among them, 93,293 patients underwent orthopedic surgery in a hospital that implemented RRS and were assigned to the RRS group, whereas 838,481 patients were assigned to the non-RRS group. In multivariable logistic regression analysis, the RRS group was not associated with in-hospital mortality after orthopedic surgery compared with the non-RRS group (odds ratio [OR] 0.93, 95% confidence interval [CI] 0.80, 1.08; P = 0.350). However, the RRS group was associated with a 14% lower postoperative complication rate after orthopedic surgery than the non-RRS group (OR 0.86, 95% CI 0.84, 0.86; P < 0.001). Conclusions: The RRS was not associated with in-hospital mortality following orthopedic surgery in South Korea. However, RRS deployment was related to a decreased risk of postoperative complications in patients undergoing orthopedic surgery. [ABSTRACT FROM AUTHOR]

Background: Little is known about differences in patient characteristics before and after implementation of the new definition of sepsis (Sepsis-3) and whether the new definition is affecting clinical practice in intensive care units. Objective: To examine and compare the clinicoepidemiologic characteristics of patients with sepsis or septic shock before and after implementation of Sepsis-3. Methods: In this population-based cohort study, a nationwide registration database in South Korea was used to identify patients with sepsis or septic shock. Patients admitted to hospitals from 2012 to 2015 constituted the Sepsis-2 group, and patients admitted from 2017 to 2020 constituted the Sepsis-3 group. Results: The study involved 443 217 patients, of whom 170 660 (38.5%) were in the Sepsis-2 group and 272 557 (61.5%) were in the Sepsis-3 group. The mean (SD) age was 73.3 (14.5) years in the Sepsis-2 group and 75.5 (14.5) years in the Sepsis-3 group. The intensive care unit admission rate was higher in the Sepsis-2 group (34.6%, 59 081 of 170 660) than in the Sepsis-3 group (21.3%, 57 997 of 272 557). Multivariable Cox regression analysis showed that 1-year all-cause mortality was 21% lower in the Sepsis-3 group than in the Sepsis-2 group (hazard ratio, 0.79; 95% CI, 0.78–0.79; P <.001). Conclusions: Implementation of the Sepsis-3 definition was associated with an increased number of patients with sepsis. Other findings suggested that patients in the Sepsis-2 group had more severe illness, with increased 1-year all-cause mortality, compared with those in the Sepsis-3 group. [ABSTRACT FROM AUTHOR]

Mucin1 (MUC1), a heterodimeric oncoprotein, containing tandem repeat structures with a high proportion of threonine, is aberrantly overexpressed in many human cancers including pancreatic cancer. Since the overall survival rate of pancreatic cancer patients has remained low for several decades, novel therapeutic approaches are highly needed. Intestinal mucin has been known to be affected by dietary threonine supply since de novo synthesis of mucin proteins is sensitive to luminal threonine concentration. However, it is unknown whether biosynthesis of MUC1 is regulated by threonine in human cancers. In this study, data provided suggests that threonine starvation reduces the level of MUC1 and inhibits the migration of MUC1-expressing pancreatic cancer cells. Interestingly, knockdown of threonyl-tRNA synthetase (TRS), an enzyme that catalyzes the ligation of threonine to its cognate tRNA, also suppresses MUC1 levels but not mRNA levels. The inhibitors of TRS decrease the level of MUC1 protein and prohibit the migration of MUC1-expressing pancreatic cancer cells. In addition, a positive correlation between TRS and MUC1 levels is observed in human pancreatic cancer cells. Concurrent with these results, the bioinformatics data indicate that co-expression of both TRS and MUC1 is correlated with the poor survival of pancreatic cancer patients. Taken together, these findings suggest a role for TRS in controlling MUC1-mediated cancer cell migration and provide insight into targeting TRS as a novel therapeutic approach to pancreatic cancer treatment.

The 2014 Surgeon General's Report on smoking and health concluded that changing cigarette designs have caused an increase in lung adenocarcinomas, implicating cigarette filter ventilation that lowers smoking machine tar yields. The Food and Drug Administration (FDA) now has the authority to regulate cigarette design if doing so would improve public health. To support a potential regulatory action, two weight-of-evidence reviews were applied for causally relating filter ventilation to lung adenocarcinoma. Published scientific literature (3284 citations) and internal tobacco company documents contributed to causation analysis evidence blocks and the identification of research gaps. Filter ventilation was adopted in the mid-1960s and was initially equated with making a cigarette safer. Since then, lung adenocarcinoma rates paradoxically increased relative to other lung cancer subtypes. Filter ventilation 1) alters tobacco combustion, increasing smoke toxicants; 2) allows for elasticity of use so that smokers inhale more smoke to maintain their nicotine intake; and 3) causes a false perception of lower health risk from "lighter" smoke. Seemingly not supportive of a causal relationship is that human exposure biomarker studies indicate no reduction in exposure, but these do not measure exposure in the lung or utilize known biomarkers of harm. Altered puffing and inhalation may make smoke available to lung cells prone to adenocarcinomas. The analysis strongly suggests that filter ventilation has contributed to the rise in lung adenocarcinomas among smokers. Thus, the FDA should consider regulating its use, up to and including a ban. Herein, we propose a research agenda to support such an effort.

Procollagen type I carboxy-terminal propeptide (PICP), derived from type I procollagen, has been identified as an indicator of type I collagen synthesis in bone matrix formation and skin recovery. PICP is a heterotrimeric glycoprotein consisting of two α1 chains (PICPα1) and one α2 chain (PICPα2). Here, we report the recombinant expression of human PICP using a mammalian expression system. Co-expression of PICPα1 and PICPα2 in HEK293F cells resulted in the production of functional PICP in the correctly assembled heterotrimeric form. Using the recombinant PICP as an antigen, we isolated PICP-specific human monoclonal antibodies from phage-displayed antibody libraries and raised rabbit polyclonal antibodies. Using those antibodies, we then developed a sandwich ELISA for PICP with a limit of detection of 1 ng/mL and a measurable range of 1-640 ng/mL. Both intra- and inter-assay imprecision values were