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.

Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H 2O 2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H 2O 2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

Purpose: The aim of this study was to analyze the age group characteristics and factors associated with the severe trauma in children who visited a regional trauma center. Methods: We reviewed children aged 18 years or younger who visited a regional trauma center, equivalent to level 1 trauma centers in the United States, in Incheon, Korea from July 2014 through December 2019. They were classified by the age groups: preschoolers (0-6 years), schoolers (7-12 years), and adolescents (13-18 years). Across the 3 age groups, event profiles, severity, and outcomes of injury were compared. Multivariable logistic regressions were used to identify factors associated with the severe trauma, defined as the Injury Severity Score of 16 or higher. Results: Among the total of 367 children, 74 (20.2%) were preschoolers, 73 (19.9%) were schoolers, and 220 (59.9%) were adolescents. The most common injury mechanisms in the preschoolers, schoolers, and adolescents were fall (40.5%), pedestrian collision (32.9%), and motorcycle accident (38.6%), respectively. The adolescents had the highest median Injury Severity Score (13 [6-23]; P < 0.001). In the multivariable analyses, the Glasgow Coma Scale of 3-8 (odds ratio [OR], 14.60; 95% confidence interval, 5.40-39.42) had the highest OR for severe trauma, followed by injury in the abdomen or pelvic contents (OR, 11.61; 95% confidence interval, 4.66-28.89). Conclusion In pediatric trauma, the mechanism and severity of injury may differ according to age groups, with the severe trauma associated with injuries to the head and torso. It is advisable to have age group-specific approaches and strategies for injury prevention.

Purpose: The aim of this study was to analyze the age group characteristics and factors associated with the severe trauma in children who visited a regional trauma center. Methods: We reviewed children aged 18 years or younger who visited a regional trauma center, equivalent to level 1 trauma centers in the United States, in Incheon, Korea from July 2014 through December 2019. They were classified by the age groups: preschoolers (0-6 years), schoolers (7-12 years), and adolescents (13-18 years). Across the 3 age groups, event profiles, severity, and outcomes of injury were compared. Multivariable logistic regressions were used to identify factors associated with the severe trauma, defined as the Injury Severity Score of 16 or higher. Results: Among the total of 367 children, 74 (20.2%) were preschoolers, 73 (19.9%) were schoolers, and 220 (59.9%) were adolescents. The most common injury mechanisms in the preschoolers, schoolers, and adolescents were fall (40.5%), pedestrian collision (32.9%), and motorcycle accident (38.6%), respectively. The adolescents had the highest median Injury Severity Score (13 [6-23]; P < 0.001). In the multivariable analyses, the Glasgow Coma Scale of 3-8 (odds ratio [OR], 14.60; 95% confidence interval, 5.40-39.42) had the highest OR for severe trauma, followed by injury in the abdomen or pelvic contents (OR, 11.61; 95% confidence interval, 4.66-28.89). Conclusion In pediatric trauma, the mechanism and severity of injury may differ according to age groups, with the severe trauma associated with injuries to the head and torso. It is advisable to have age group-specific approaches and strategies for injury prevention.

Aldose reductase (AR) protein, a member of the NADPH-dependent aldo-keto reductase family, reduces a wide range of aldehydes and enhances cell survival by inhibition of oxidative stress. Oxidative stress is known as one of the major pathological factor in ischemia. Since the precise function of AR protein in ischemic injury is fully unclear, we examined the function of AR protein in hippocampal neuronal (HT-22) cells and in an animal model of ischemia in this study. Cell permeable Tat-AR protein was produced by fusion of protein transduction domain in Tat for delivery into the cells. Tat-AR protein transduced into HT-22 cells and significantly inhibited cell death and regulated the mitogen-activate protein kinases (MAPKs), Bcl-2, Bax, and Caspase-3 under oxidative stress condition. In an ischemic animal model, Tat-AR protein transduced into the brain tissues through the blood-brain barrier (BBB) and drastically decreased neuronal cell death in hippocampal CA1 region. These results indicate that transduced Tat-AR protein has protective effects against oxidative stress-induced neuronal cell death in vitro and in vivo, suggesting that Tat-AR protein could be used as potential therapeutic agent in ischemic injury.
Aldehyde Reductase ; Aldehydes ; Blood-Brain Barrier ; Brain ; CA1 Region, Hippocampal ; Caspase 3 ; Cell Death ; Cell Survival ; Humans ; In Vitro Techniques ; Ischemia ; Models, Animal ; Neurons ; Oxidative Stress ; Oxidoreductases ; Protein Kinases

A 52-year-old woman with rheumatoid arthritis who had been treated with prednisone and hydroxychloroquine for >12 years presented with chest discomfort and a seizure. She was diagnosed with restrictive cardiomyopathy combined with sick sinus syndrome. A myocardial muscle biopsy was performed to identify the underlying cardiomyopathy, which showed marked muscle fiber hypertrophy, fiber dropout, slightly increased interstitial fibrous connective tissue, and extensive cytoplasmic vacuolization of the myocytes under light microscopy. Electron microscopy of the myocytes demonstrated dense, myeloid, and curvilinear bodies. The diagnosis of hydroxychloroquine-induced cardiomyopathy was made based on the clinical, hemodynamic, and pathologic findings. This is the first case report describing chloroquine-induced cardiomyopathy involving the heart conduction system.
Arthritis, Rheumatoid ; Biopsy ; Cardiomyopathies ; Cardiomyopathy, Restrictive ; Connective Tissue ; Cytoplasm ; Female ; Heart Conduction System ; Hemodynamics ; Humans ; Hydroxychloroquine ; Hypertrophy ; Light ; Microscopy ; Microscopy, Electron ; Middle Aged ; Muscle Cells ; Muscles ; Patient Dropouts ; Prednisone ; Seizures ; Sick Sinus Syndrome ; Thorax

As part of an initial inquiry into the function of the outer membrane proteins (OMPs) of Helicobacter pylori Korean strain 51, we have conducted an extensive proteome analysis via quadrupole time of flight (Q-TOF) mass spectrometry (MS). Fifty one OMPs of H. pylori were purified using sarcosine and resolved via two-dimensional electrophoresis with immobilized pH gradient strips. The most abundant proteins were observed in the alkaline pI regions (6.0~11.0) at molecular masses between 10~100 KDa. Here, 15 spots were identified, representing 9 types of genes (KHP0852, KHP0853, KHP1353, KHP1017, KHP0172, KHP0076, KHP0617, KHP1069, KHP0614) from the sarcosin-insoluble fraction of H. pylori 51. These may be employed in the characterization of the OMPs of H. pylori 51, which will help to identify new potential target proteins for vaccine development and drug therapy.
Electrophoresis ; Helicobacter ; Helicobacter pylori ; Mass Spectrometry ; Membrane Proteins ; Membranes ; Proteins ; Proteome ; Proton-Motive Force ; Sarcosine ; Sprains and Strains

The protein identity of sarcosine-insoluble outer membrane proteins (OMPs) of Helicobacter pylori J99 was determined with the basic study of understanding the function of proteins. A sarcosine-insoluble OMPs was resolved by two-dimensional electrophoresis with immobilized pH gradient strips. The most abundant proteins were shown in the alkaline pI regions (6.0~11.0) with molecular masses of 10 to 100 kDa. We have performed an extensive proteome analysis by quadrupole time of flight (Q-TOF) mass spectrometry (MS). Here, of 50 spots processed, 42 spots were identified, which represented 16 genes and we newly detected 8 kinds of proteins (JHP0119, JHP0388, JHP1046, JHP1405, JHP0073, JHP0551, JHP1382, JHP0552) from the sarcosin-insoluble fraction of H. pylori J99. Those may be used to elucidate the characterization of the OMPs of H. pylori J99, which will help identify new potential target proteins for vaccine development and drug therapy.
Electrophoresis ; Helicobacter ; Helicobacter pylori ; Mass Spectrometry ; Membrane Proteins ; Membranes ; Proteins ; Proteome ; Proton-Motive Force ; Tandem Mass Spectrometry

PURPOSE: The aim of this study was to know whether and how tamsulosin induces apoptosis of normal rat prostate cells, and the relationship between apoptosis and clusterin expression. MATERIALS AND METHODS: We used a prostate cell line, NRP-152 cells which are the basal epithelium cell originated from rat prostate. The NRP-152 cells were treated with various concentrations(50, 100, 200, 400 uM) of tamsulosin for 24 h. To evaluate apoptosis, the cultured NRP-152 cells were stained with Heochst 33258 and Propidium Iodide (PI) without fixation. We also examined DNA fragmentation analysis to confirm apoptosis. In addition, to elucidate the signal transduction pathway by which apoptosis is induced, we examined Bcl-2 family proteins such as Bcl-2, Bax, Bad, Bcl-xL, and Bim by real-time RT-PCR. RESULTS: After tamsulosin treatment, the rate of apoptosis was 25% at 100 micrometer, 50% at 200 micrometer, and 63% at 400 micrometer, whereas the rate of necrosis was 10% at 100 micrometer, 38% at 200 micrometer, and 56% at 400 micrometer. DNA fragmentation was also gradually increased and the highest at 400 micrometer, similar to apoptotic cell rates. As a result of real-time RT-PCR, there was significant difference of Bcl-2 and Bim mRNA expression among the groups. Expression of clusterin protein was significantly increased after treatment of tamsulosin, even as low as 50 micrometer concentration. CONCLUSION: These results demonstrate that tamsulosin causes the cell death of NRP-152 cells, displaying low concentration of tamsulosin induces apoptosis, but high concentration occurs necrosis. Bim, a proapoptotic factor of the Bcl-2 family, expression was increased in the cells treated with tamsulosin, whereas Bcl-2 expression was decreased. The present study suggests that clusterin may play a role in the process of apoptosis induced by tamsulosin and Bim could be involved in the apoptosis.
Animals ; Apoptosis* ; Cell Death ; Cell Line ; Clusterin* ; DNA Fragmentation ; Epithelium ; Humans ; Necrosis ; Propidium ; Prostate ; Rats ; RNA, Messenger ; Signal Transduction