Background: Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. Methods: From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation–Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. Results: Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence inter val [CI], 0.55– 0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% 0.56–0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79–1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65–2.17; P = 0.582). Conclusion In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.

Background/Aims: Although a management fee for hospitalist service was established in Korea, the number of hospitalists required for the system to run remains outmatched. Methods: In January 2020 and February 2022, before and after the establishment of the hospitalist fee system respectively, cross-sectional online surveys were conducted among internal medicine board-certified hospitalists. Results: There were 59 and 64 respondents in the 2020 and 2022 surveys, respectively. The percentage of respondents who cited financial benefits as a motive for becoming a hospitalist was higher in the 2022 survey than in the 2020 survey (34.4% vs. 10.2%; p = 0.001). The annual salary of respondents was also higher in the 2022 survey than in the 2020 survey (mean, 182.9 vs. 163.0 million in South Korean Won; p = 0.006). A total of 81.3% of the respondents were willing to continue a hospitalist career in the 2022 survey. In multivariate regression analysis, the possibility of being appointed as a professor was found to be an independent predictive factor of continuing a hospitalist career (odds ratio, 4.00; 95% confidence interval, 1.09–14.75; p = 0.037). Conclusions Since the establishment of the hospitalist fee system, monetary compensation has improved for hospitalists. The possibility of being appointed as a professor could predict long-term work as hospitalists.

BACKGROUND/OBJECTIVES: Abeliophyllum distichum is a plant endemic to Korea, containing several beneficial natural compounds. This study investigated the effect of A. distichum leaf extract (ALE) on adipocyte differentiation.MATERIALS/METHODS: The cytotoxic effect of ALE was analyzed using cell viability assay.3T3-L1 preadipocytes were differentiated using induction media in the presence or absence of ALE. Lipid accumulation was confirmed using Oil Red O staining. The mRNA expression of adipogenic markers was measured using RT-PCR, and the protein expressions of mitogenactivated protein kinase (MAPK) and peroxisome proliferator-activated receptor gamma (PPARγ) were measured using western blot. Cell proliferation was measured by calculating the incorporation of Bromodeoxyuridine (BrdU) into DNA. RESULTS: ALE reduced lipid accumulation in differentiated adipocytes, as indicated by Oil Red O staining and triglyceride assays. Treatment with ALE decreased the gene expression of adipogenic markers such as Pparγ, CCAAT/enhancer binding protein alpha (C/ebpα), lipoprotein lipase, adipocyte protein-2, acetyl-CoA carboxylase, and fatty acid synthase.Also, the protein expression of PPARγ was reduced by ALE. Treating the cells with ALE at different time points revealed that the inhibitory effect of ALE on adipogenesis is higher in the early period treatment than in the terminal period. Furthermore, ALE inhibited adipocyte differentiation by reducing the early phase of adipogenesis and mitotic clonal expansion. This was indicated by the lower number of cells in the Synthesis phase of the cell cycle (labeled using BrdU assay) and a decrease in the expression of early adipogenic transcription factors such as C/ebpβ and C/ebpδ. ALE suppressed the phosphorylation of MAPK, confirming that the effect of ALE was through the suppression of early phase of adipogenesis. CONCLUSIONS Altogether, the results of the present study revealed that ALE inhibits lipid accumulation and may be a potential agent for managing obesity.

BACKGROUND/OBJECTIVES: Abeliophyllum distichum is a plant endemic to Korea, containing several beneficial natural compounds. This study investigated the effect of A. distichum leaf extract (ALE) on adipocyte differentiation.MATERIALS/METHODS: The cytotoxic effect of ALE was analyzed using cell viability assay.3T3-L1 preadipocytes were differentiated using induction media in the presence or absence of ALE. Lipid accumulation was confirmed using Oil Red O staining. The mRNA expression of adipogenic markers was measured using RT-PCR, and the protein expressions of mitogenactivated protein kinase (MAPK) and peroxisome proliferator-activated receptor gamma (PPARγ) were measured using western blot. Cell proliferation was measured by calculating the incorporation of Bromodeoxyuridine (BrdU) into DNA. RESULTS: ALE reduced lipid accumulation in differentiated adipocytes, as indicated by Oil Red O staining and triglyceride assays. Treatment with ALE decreased the gene expression of adipogenic markers such as Pparγ, CCAAT/enhancer binding protein alpha (C/ebpα), lipoprotein lipase, adipocyte protein-2, acetyl-CoA carboxylase, and fatty acid synthase.Also, the protein expression of PPARγ was reduced by ALE. Treating the cells with ALE at different time points revealed that the inhibitory effect of ALE on adipogenesis is higher in the early period treatment than in the terminal period. Furthermore, ALE inhibited adipocyte differentiation by reducing the early phase of adipogenesis and mitotic clonal expansion. This was indicated by the lower number of cells in the Synthesis phase of the cell cycle (labeled using BrdU assay) and a decrease in the expression of early adipogenic transcription factors such as C/ebpβ and C/ebpδ. ALE suppressed the phosphorylation of MAPK, confirming that the effect of ALE was through the suppression of early phase of adipogenesis. CONCLUSIONS Altogether, the results of the present study revealed that ALE inhibits lipid accumulation and may be a potential agent for managing obesity.

PURPOSE: This study examined the immunological activity and optimized the mixture conditions of Sargassum horneri (S. horneri) extracts in vitro and in vivo models.METHODS: S. horneri was extracted using three different methods: hot water extraction (HWE), 50% ethanol extraction (EE), and supercritical fluid extraction (SFE). Splenocyte proliferation and cytokine production (Interleukin-2 and Interferon-γ) were measured using a WST-1 assay and enzyme-linked immunosorbent assay, respectively. The levels of nitric oxide and T cell activation production were measured using a Griess assay and flow cytometry, respectively. The natural killer (NK) cell activity was determined using an EZ-LDH kit.RESULTS: Among the three different types of extracts, HWE showed the highest levels of splenocyte proliferation and cytokine production in vitro. In the animal model, three different types of extracts were administrated for 14 days (once/day) at 50 and 100 mg/kg body weight. HWE and SFE showed a high level of splenocyte proliferation and cytokine production in the with and without mitogen-treated groups, whereas EE administration did not induce the splenocyte activation. When RAW264.7 macrophage cells were treated with different mixtures (HWE with 5, 10, 15, 20% of SFE) to determine the optimal mixture ratio of HWE and SFE, the levels of nitric oxide and cytokine production increased strongly in the HWE with 5% and 10% of SFE containing group. In the animal model, HWE with 5% and 10% of SFE mixture administration increased the levels of splenocyte proliferation, cytokine production, and activated CD4⁺ cell population significantly, with the highest level observed in the HWE with 5% of SFE group. Moreover, the NK cell activity was increased significantly in the HWE with 5% of SFE mixture-treated group compared to the control group.CONCLUSION: The optimal mixture condition of S. horneri with immune-enhancing activity is the HWE with 5% of SFE mixture. These results confirmed that the extracts of S. horneri and its mixtures are potential candidate materials for immune enhancement.
Body Weight ; Chromatography, Supercritical Fluid ; Enzyme-Linked Immunosorbent Assay ; Ethanol ; Flow Cytometry ; In Vitro Techniques ; Killer Cells, Natural ; Macrophages ; Models, Animal ; Nitric Oxide ; Sargassum ; Water

PURPOSE: Sargassum horneri (S. horneri) is a species of brown macroalgae that is common along the coast of Japan and Korea. The present study investigated the immuno-modulatory effects of different types of S. horneri extracts in RAW264.7 macrophages. METHODS: S. horneri was extracted by three different methods, hot water extraction, 50% ethanol extraction, and supercritical fluid extraction. Cell viability was then measured by MTT assay, while the production levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO) were measured by enzyme-linked immunosorbent assay and Griess assay, respectively. The expression and activation levels of inducible NO synthase (iNOS), mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) were examined by western blot analysis. RESULTS: The three different S. horneri extracts were nontoxic against RAW 264.7 cells up to 50 µg/mL, among which treatment with hot water extract (HWE) of S. horneri significantly enhanced the production of TNF-α, IL-6, and NO in a dose-dependent manner. Hot water extract of S. horneri also increased the expression level of iNOS, suggesting that up-regulation of iNOS expression by HWE of S. horneri was responsible for the induction of NO production. In addition, treatment of RAW 264.7 macrophages with HWE of S. horneri increased the phosphorylation levels of ERK, p38 and JNK. Furthermore, the activation and subsequent nuclear translocation of NF-κB was enhanced upon treatment with HWE of S. horneri, indicating that HWE of S. horneri activates macrophages to secrete TNF-α, IL-6 and NO and induces iNOS expression via activation of the NF-κB and MAPKs signaling pathways. CONCLUSION: Taken together, these findings suggest that HWE of S. horneri possesses potential as a functional food with immunomodulatory activity.
Blotting, Western ; Cell Survival ; Chromatography, Supercritical Fluid ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Ethanol ; Functional Food ; Interleukin-6 ; Japan ; Korea ; Macrophages* ; Necrosis ; Nitric Oxide ; Nitric Oxide Synthase ; Phosphorylation ; Protein Kinases ; RAW 264.7 Cells ; Sargassum* ; Seaweed ; Up-Regulation ; Water

It has been found that 4-isopropyl-2,6-bis(1-phenylethyl)phenol (KTH-13), a novel compound isolated from Cordyceps bassiana, is able to suppress tumor cell proliferation by inducing apoptosis. To mass-produce this compound, we established a total synthesis method. Using those conditions, we further synthesized various analogs with structural similarity to KTH-13. In this study, we aimed to test their anti-cancer activity by measuring anti-proliferative and pro-apoptotic activities. Of 8 compounds tested, 4-methyl-2,6-bis(1-phenylethyl)phenol (KTH-13-Me) exhibited the strongest anti-proliferative activity toward MDA-MB 231 cells. KTH-13-Me also similarly suppressed the survival of various cancer cell lines, including C6 glioma, HCT-15, and LoVo cells. Treatment of KTH-13-Me induced several apoptotic signs in C6 glioma cells, such as morphological changes, induction of apoptotic bodies, and nuclear fragmentation and chromatin condensation. Concordantly, early-apoptotic cells were also identified by staining with FITC-Annexin V/PI. Moreover, KTH-13-Me highly enhanced the activation of caspase-3 and caspase-9, and decreased the protein level of Bcl-2. In addition, the phosphorylation levels of Src and STAT3 were diminished in KTH-13-Me-treated C6 cells. Therefore, these results suggest that KTH-13-Me can be developed as a novel anti-cancer drug capable of blocking proliferation, inducing apoptosis, and blocking cell survival signaling in cancer cells.
Apoptosis ; Caspase 3 ; Caspase 9 ; Cell Line ; Cell Proliferation ; Cell Survival ; Chromatin ; Cordyceps ; Extracellular Vesicles ; Glioma ; Methods ; Phosphorylation

The aim of this study was to verify subacute oral dose toxicity of positively charged 100 nm zinc oxide (ZnO(AE100[+])) nanoparticles (NPs) in Sprague-Dawley rats. ZnO(AE100[+]) NPs were administered to rats of each sex by gavage at 0, 500, 1,000, and 2,000 mg/kg/day for 14 days. During the study period, clinical signs, mortality, body weight, food consumption, hematology, serum biochemistry, gross pathology, organ weight, and histopathology were examined. Increased mortality and clinical signs, decreased body weight, feed consumption, hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet (PT), and lymphocyte (LYM) and increased white blood cells (WBCs), neutrophils (NEUs), alkaline phosphatase (ALP), and histopathological alterations in the spleen, stomach, and pancreas were observed at 2,000 mg/kg/day. Increased clinical signs, decreased body weight, feed consumption, HB, HCT, MCV, MCH, MCHC, and LYM and increased WBCs, NEUs, ALP, and histopathological alterations in the spleen, stomach, and pancreas were seen at 1,000 mg/kg/day. Increased clinical signs, decreased MCV and MCH and increased histopathological alterations in the stomach and pancreas were found at 500 mg/kg/day. These results suggest that the target organs were the spleen, stomach, and pancreas in rats. The no-observed-adverse-effect level was <500 mg/kg for both sexes.
Alkaline Phosphatase ; Animals ; Biochemistry ; Blood Platelets ; Body Weight ; Erythrocyte Indices ; Hematocrit ; Hematology ; Leukocytes ; Lymphocytes ; Mortality ; Nanoparticles* ; Neutrophils ; No-Observed-Adverse-Effect Level ; Organ Size ; Pancreas ; Pathology ; Rats* ; Rats, Sprague-Dawley ; Spleen ; Stomach ; Zinc Oxide* ; Zinc*

Behcet's disease (BD) is a multi-systemic inflammatory disease of unknown origin that affects nearly all organs including the nervous system. Although the neurological involvement is less frequent than other major presentations, it is important because it can produce severe disabilities. Peripheral nervous system manifestations are relatively rare in BD. Although few cases of peripheral neuropathy or myopathy have been reported in BD, they are cases of multiple neuropathies, sensorimotor peripheral neuropathy, or neuropathy autonomic dysfunction. Guillain-Barre syndrome (GBS), also known as an acute inflammatory demyelinating polyneuropathy, is an acute demyelinating polyradiculopathy of uncertain etiology. No case of GBS associated with BD in Korea has been reported. Herein we report on a patient of BD who suffered from weakness of extremities and was diagnosed as GBS.
Extremities ; Guillain-Barre Syndrome* ; Humans ; Korea ; Muscular Diseases ; Nervous System ; Peripheral Nervous System ; Peripheral Nervous System Diseases ; Polyradiculopathy

Nephrotic syndrome is characterized by hypercoagulability and thrombosis of the renal and deep veins. We describe a case of unusual thrombosis in the portal and superior mesenteric veins of a 41-year-old female, admitted for treatment of abdominal pain, who simultaneously presented with nephrotic syndrome and acute pancreatitis. Laboratory analysis revealed hypoalbuminemia, hyperlipidemia, and proteinuria. Abdominal computed tomography revealed acute pancreatitis, thrombosis at the portal and superior mesenteric veins, and ischemic changes in the colon and small intestines. Anticoagulation therapy was started immediately. Abdominal pain was subsequently reduced and the ischemic lesion disappeared. Warfarin use could not be terminated immediately. Empirical steroid therapy commenced without a kidney biopsy. Complete remission occurred after 4 weeks. Following warfarin cessation, a kidney biopsy was performed, confirming the diagnosis of minimal change disease.
Abdominal Pain ; Adult ; Biopsy ; Colon ; Diagnosis ; Female ; Humans ; Hyperlipidemias ; Hypoalbuminemia ; Intestine, Small ; Kidney ; Mesenteric Veins ; Nephrosis, Lipoid ; Nephrotic Syndrome ; Pancreatitis* ; Portal Vein* ; Proteinuria ; Thrombophilia ; Thrombosis* ; Veins ; Warfarin