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This paper introduces the design concept of a dual-functional molecular dyad tailored specifically for solution-processable organic light-emitting diodes (OLEDs). Cy-tmCPBN, characterized by an asymmetric molecular dyad structure, integrates a host unit (tmCP) and a multiple-resonance (MR) emitter (CzBN) via a non-conjugated cyclohexane linker. Cy-tmCPBN exhibited efficient intramolecular energy transfers (EnTs) from tmCP to the CzBN unit, as confirmed by time-resolved fluorescence experiments. The fluorescence lifetime of the tmCP unit was approximately three times shorter in a highly diluted solution of Cy-tmCPBN than in a mixed solution of Cy-tmCP and Cy-CzBN. In addition, Cy-tmCPBN exhibited excellent solubility and film-forming ability, making it suitable for solution processing. Notably, OLEDs utilizing Cy-tmCPBN achieved over twice the brightness and improved external quantum efficiency of 12.3% compared to OLEDs using Cy-CzBN with the same concentration of CzBN in the emitting layer. The improved OLED performance can be explained by the increased EnT efficiency from Cy-tmCP to Cy-tmCPBN and the intramolecular EnT within Cy-tmCPBN. In our dual-functional dyad, incorporating both host and emitter units in an asymmetric molecular dyad structure, we induced a positive synergy effect with the host moiety, enhancing OLED performance through intramolecular EnT.
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BACKGROUND: Remimazolam is not only associated with a lower incidence of respiratory depression than propofol but also in itself has the risk of respiratory depression. OBJECTIVE: We investigated respiratory depression following remimazolam infusion, targeting different effect-site concentrations using target-controlled infusion. DESIGN: A prospective, double-blind, randomised controlled study. SETTING: Tertiary hospital, Suwon, South Korea, from April 2022 to November 2022. PARTICIPANTS: One hundred and seven patients scheduled for general anaesthesia were randomised into three groups targeting remimazolam effect-site concentrations of 500 (RMZ-500) (nâ=â36), 1000 (RMZ-1000) (nâ=â35) and 1500ângâml-1 (RMZ-1500) (nâ=â36). INTERVENTIONS: Remimazolam was solely infused for 10âmin according to target effect-site concentrations. According to the degree of SpO2 decrease, oxygen desaturations were managed with the following respiratory supports: jaw-thrust for SpO2 less than 97%, 100% oxygen delivery for SpO2 less than 93% and assisted ventilation for SpO2 less than 90%. MAIN OUTCOME MEASURES: The incidence of each respiratory support, along with respiratory variables (at baseline, 5âmin and 10âmin after remimazolam infusion) and loss of consciousness were observed for 10âmin after remimazolam target-controlled infusion. RESULTS: Both RMZ-1000 and RMZ-1500 required more frequent respiratory support than RMZ-500 (both Pâ<â0.001), with nearly identical frequencies between RMZ-1000 and RMZ-1500. In terms of respiratory support, the incidence of assisted ventilation was significantly lower in RMZ-500 (2.8%) than RMZ-1000 (48.6%) and RMZ-1500 (50%) (Pâ<â0.001). RMZ-1000 and RMZ-1500 achieved loss of consciousness in all patients; RMZ-500 only achieved loss of consciousness in 86.1% of patients (Pâ=â0.010). In patients who maintained spontaneous respiration, tidal volume decreased by 41 to 48% and respiratory rate increased by 118 to 158% at 5 and 10âmin, significantly compared to baseline in all groups (Pâ<â0.001). CONCLUSIONS: Remimazolam infusion, like that of other benzodiazepines, led to respiratory depression, which was more prominent at higher target effect-site concentrations. Therefore, appropriate countermeasures should be developed to prevent oxygen desaturation. TRIAL REGISTRATION: CRIS (https://cris.nih.go.kr), identifier: KCT0006952.
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BACKGROUND: This study aimed to determine whether self-regulation acts as a mediating factor in the relationship between obesity-related stress and weight control behavior, targeting Korean female college students. Obesity-related stress and weight control behaviors are important factors affecting an individual's health and well-being, and self-control, a psychological trait, can play a pivotal role in regulating how individuals respond to stress and engage in weight management behaviors. METHODS: This study employed a descriptive correlational design. A total of 109 female college students with overweight and obesity participated in the study. We used a self-report questionnaire to measure obesity-related stress, self-control, and degree of weight control behavior. Data were analyzed using descriptive statistics, Pearson's correlation coefficient analysis, and bootstrapping using Hayes' PROCESS macro for mediation. RESULTS: Significant relationships between obesity-related stress and weight control behavior (r = 0.25, p < 0.001), obesity-related stress and self-control (r = -0.36, p < 0.001), and weight control behavior and self-control (r = 0.26, p < 0.001) were observed. Self-control showed an indirect mediating effect on the relationship between obesity-related stress and weight control behavior (Β = 0.37, p = 0.001). CONCLUSIONS: Through the research results, it was confirmed that self-control is a factor that has a mediating effect in the relationship between obesity-related stress and weight control behavior among female college students with overweight and obesity. These results underscore the importance of addressing self-control strategies in interventions aimed at promoting healthy weight management among female college students with overweight or obesity.
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BACKGROUND: Postoperative delirium after organ transplantation can lead to increased length of hospital stay and mortality. Because pain is an important risk factor for delirium, perioperative analgesia with intrathecal morphine (ITM) may mitigate postoperative delirium development. We evaluated if ITM reduces postoperative delirium incidence in living donor kidney transplant (LDKT) recipients. METHODS: Two hundred ninety-six patients who received LDKT between 2014 and 2018 at our hospital were retrospectively analyzed. Recipients who received preoperative ITM (ITM group) were compared with those who did not (control group). The primary outcome was postoperative delirium based on the Confusion Assessment Method for Intensive Care Unit results during the first 4 postoperative days. RESULTS: Delirium occurred in 2.6% (4/154) and 7.0% (10/142) of the ITM and control groups, respectively. Multivariable analysis showed age (odds ratio [OR]: 1.07, 95% CI: 1.01-1.14; P = .031), recent smoking (OR: 7.87, 95% CI: 1.43-43.31; P = .018), preoperative psychotropics (OR: 23.01, 95% CI: 3.22-164.66; P = .002) were risk factors, whereas ITM was a protective factor (OR: 0.23, 95% CI: 0.06-0.89; P = .033). CONCLUSIONS: Preoperative ITM showed an independent association with reduced post-LDKT delirium. Further studies and the development of regional analgesia for delirium prevention may enhance the postoperative recovery of transplant recipients.
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Analgésicos Opioides , Delírio , Injeções Espinhais , Transplante de Rim , Doadores Vivos , Morfina , Dor Pós-Operatória , Humanos , Transplante de Rim/efeitos adversos , Morfina/administração & dosagem , Masculino , Feminino , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/etiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Delírio/prevenção & controle , Delírio/etiologia , Delírio/epidemiologia , Analgésicos Opioides/administração & dosagem , Adulto , Fatores de Risco , Agitação Psicomotora/prevenção & controle , Agitação Psicomotora/etiologia , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-OperatóriosRESUMO
Distant metastasis is the leading cause of death in breast cancer (BC). The timing of distant metastasis differs according to subtypes of BCs and there is a need for identification of biomarkers for the prediction of early and late metastasis. To identify biomarker candidates whose abundance level can discriminate metastasis types, we performed a high-throughput proteomics assay using tissue samples from BCs with no metastasis, late metastasis, and early metastasis, processed data with machine learning-based feature selection, and found that low VWA5A could be responsible for shorter duration of metastasis-free interval. Low expression of VWA5A gene in METABRIC cohort was associated with poor survival in BCs, especially in hormone receptor (HR)-positive BCs. In-vitro experiments confirmed tumor suppressive effect of VWA5A on BCs in HR+ and triple-negative BC cell lines. We found that expression of VWA5A can be assessed by immunohistochemistry (IHC) on archival tissue samples. Decreasing nuclear expression of VWA5A was significantly associated with advanced T stage and lymphatic invasion in consecutive BCs of all subtypes. We discovered lower expression of VWA5A as the potential biomarker for metastasis-prone BCs, and our results support the clinical utility of VWA5A IHC, as an adjunctive tools for prognostication of BCs.
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Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Feminino , Humanos , Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Prognóstico , Neoplasias de Mama Triplo Negativas/patologia , Proteínas Supressoras de TumorRESUMO
BACKGROUND: Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multipotent protein that plays essential roles in cellular responses to oxidative stress. METHODS: To examine the role of APE1/Ref-1 in ischemia-reperfusion (I/R) injuries and hydrogen peroxide (H2O2)-induced renal tubular apoptosis, we studied male C57BL6 mice and human proximal tubular epithelial (HK-2) cells treated with H2O2 at different concentrations. The colocalization of APE1/Ref-1 in the proximal tubule, distal tubule, thick ascending limb, and collecting duct was observed with confocal microscopy. The overexpression of APE1/Ref-1 with knockdown cell lines using an APE1/Ref-1-specific DNA or small interfering RNA (siRNA) was used for the apoptosis assay. The promotor activity of nuclear factor kappa B (NF-κB) was assessed and electrophoretic mobility shift assay was conducted. RESULTS: APE1/Ref-1 was predominantly localized to the renal tubule nucleus. In renal I/R injuries, the levels of APE1/Ref-1 protein were increased compared with those in kidneys subjected to sham operations. The overexpression of APE1/Ref-1 in HK-2 cells enhanced the Bax/Bcl-2 ratio as a marker of apoptosis. Conversely, the suppression of APE1/Ref-1 expression by siRNA in 1-mM H2O2-treated HK-2 cells decreased the Bax/Bcl-2 ratio, the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38, c-Jun N-terminal kinase (JNK) 1/2, and NF-κB. In HK-2 cells, the promoter activity of NF-κB increased following H2O2 exposure, and this effect was further enhanced by APE1/Ref-1 transfection. CONCLUSION: The inhibition of APE1/Ref-1 with siRNA attenuated H2O2-induced apoptosis through the modulation of mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 and the nuclear activation of NF-κB and proapoptotic factors.
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The Shaan virus is a new paramyxovirus species recently isolated from an insectivorous bat. Therefore, its replication characteristics remain unclear. We used transcriptome analysis and molecular experiments to examine host cell responses in human A549, HEK293, and monkey MARC-145 cell lines infected with the Shaan virus (ShaV/B16-40). Transcriptome data showed that Shaan virus infection induced innate immune responses associated with defense mechanisms against viral infection in all infected host cells. In real-time RT-PCR, IFN-α, -ß and -λ1 were significantly upregulated in response to infection with Shaan virus in A549 and HEK-293 cells. However, the expression of IFN-α and -λ1 did not change in MARC-145 infected cells, while IFN-ß significantly increased compared to the control in all the infected cell lines. In DEG analysis, the viperin expression pattern by Shaan virus infection varied depending on the host cell types or their origins. Viperin was highly induced at the RNA level by Shaan virus infection, and viperin protein expression was detected by western blotting. Although viperin, an ISG, has broad inhibitory effects on a range of viral pathogens, viperin knockdown or knock-in in the infected cells indicated that this protein did not markedly affect Shaan virus replication. Interestingly, these effects were independent of CMPK2 expression, which is beneficial for the antiviral effects of viperin. Therefore, the present results suggest that Shaan virus might have a strategy to evade the antiviral effect of viperin or not be significantly affected by viperin.
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Genotype 4 (G4) Eurasian avian-like lineage swine H1N1 influenza A viruses, which are reassortants containing sequences from the pandemic 2009 H1N1 virus lineage, triple-reassortant-lineage internal genes, and EA-lineage external genes, have been reported in China since 2013. These have been predominant in pig populations since 2016 and have exhibited pandemic potential. In this study, we developed a one-step multiplex RT-qPCR assay targeting the M, HA1, and PB2 genes to detect G4 and related EA H1N1 viruses, with detection limits of 1.5 × 101 copies/µL and 1.15 × 10-2 ng/µL for the purified PCR products and RNA templates, respectively. The specificity of the detection method was confirmed using various influenza virus subtypes. When the one-step multiplex RT-qPCR assay was applied to swine respiratory samples collected between 2020 and 2022 in Korea, a virus related to G4 EA H1N1 strains was detected. Phylogenetic analysis based on portions of all eight genome segments showed that the positive sample contained HA, NA, PB2, NS, and NP genes closely related to those of G4 EA H1N1 viruses, confirming the ability of our assay to accurately detect G4 EA H1N1 viruses in the field.
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Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Infecções por Orthomyxoviridae , Doenças dos Suínos , Suínos , Animais , Vírus da Influenza A Subtipo H1N1/genética , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/veterinária , Filogenia , Fazendas , Vírus Reordenados/genética , Aves , Genótipo , República da Coreia/epidemiologia , Doenças dos Suínos/epidemiologiaRESUMO
OBJECTIVE: Famotidine, an H2 receptor antagonist (H2RA), is mainly prescribed to alleviate the early symptoms of gastritis. Our aim was to explore the possibilities of low-dose esomeprazole as a treatment of gastritis as well as the pharmacodynamic (PD) properties of esomeprazole and famotidine. MATERIALS AND METHODS: A randomized, multiple-dose, 6-sequence, 3-period crossover study was conducted with a 7-day washout between periods. For each period, the subjects were administered one dose of esomeprazole 10 mg or famotidine 20 mg or esomeprazole 20 mg each day. To evaluate the PDs, the 24-hour gastric pH was recorded after single and multiple doses. The mean percentage of time during which the gastric pH was above 4 was evaluated for PD assessment. To confirm the pharmacokinetic (PK) characteristics of esomeprazole, blood was collected for up to 24 hours after multiple doses. RESULTS: 26 subjects completed the study. Following the multiple doses of esomeprazole 10 mg, esomeprazole 20 mg, and famotidine 20 mg, the mean percentages of time during which the gastric pH was above 4 over the course of 24 hour were 35.77 ± 19.56%, 53.75 ± 20.55%, and 24.48 ± 17.36%, respectively. After multiple doses, the time of peak plasma concentration at steady state (tmax,ss) was 1.00 and 1.25 hours for 10 and 20 mg of esomeprazole, respectively. The geometric mean ratio and its 90% confidence interval of area under the plasma drug concentration-time curve in steady state (AUCT,ss) and maximum concentration of drug in plasma in steady state (Cmax,ss) for esomeprazole 10 mg compared to 20 mg were 0.3654 (0.3381 - 0.3948) and 0.5066 (0.4601 - 0.5579), respectively. CONCLUSION: The PD parameters of esomeprazole 10 mg were comparable to those of famotidine after multiple doses. These findings provide support for further evaluating the use of 10 mg of esomeprazole as a treatment option for gastritis.
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Esomeprazol , Gastrite , Humanos , Esomeprazol/farmacocinética , Famotidina/farmacologia , Voluntários Saudáveis , Estudos Cross-Over , Gastrite/diagnóstico , Gastrite/tratamento farmacológicoRESUMO
Supraglottic airway (SGA) may have advantages over endotracheal tube (ETT) regarding laryngospasm, coughing, sore throat, and hemodynamic changes; however, studies on the use of SGA in laparoscopic donor nephrectomy (LDN) are lacking. Here, we aimed to confirm the safety and feasibility of second-generation SGA in LDN and compare them with those of ETT. Enrolled adult donors (aged > 18 years) who underwent LDN between August 2018 and November 2021 were divided into two groups-ETT vs. SGA. Airway pressure, lung compliance, desaturation, and hypercapnia were recorded during surgery. After propensity score matching for baseline characteristics and surgical duration, 82 and 152 donors were included in the ETT and SGA groups, respectively, and their outcomes were compared. The peak airway pressure was lower in the SGA group than in the ETT group 5 min after pneumoperitoneum. Dynamic lung compliance was higher in the SGA group than in the ETT group during surgery. There were no cases of intraoperative desaturation, hypercapnia, or postoperative aspiration pneumonitis. The use of second-generation SGA, a safe alternative to ETT for LDN, resulted in reduced airway resistance and increased lung compliance, which suggests its benefits for airway management in kidney donors.
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Hipercapnia , Laparoscopia , Adulto , Humanos , Doadores de Tecidos , Laparoscopia/efeitos adversos , Manuseio das Vias Aéreas , Nefrectomia/efeitos adversosRESUMO
BACKGROUND: Postoperative delirium is a common complication that is distressing. This study aimed to demonstrate a prediction model for delirium. METHODS: Among 203,374undergoing non-cardiac surgery between January 2011 and June 2019 at Samsung Medical Center, 2,865 (1.4%) were diagnosed with postoperative delirium. After comparing performances of machine learning algorithms, we chose variables for a prediction model based on an extreme gradient boosting algorithm. Using the top five variables, we generated a prediction model for delirium and conducted an external validation. The Kaplan-Meier and Cox survival analyses were used to analyse the difference of delirium occurrence in patients classified as a prediction model. RESULTS: The top five variables selected for the postoperative delirium prediction model were age, operation duration, physical status classification, male sex, and surgical risk. An optimal probability threshold in this model was estimated to be 0.02. The area under the receiver operating characteristic (AUROC) curve was 0.870 with a 95% confidence interval of 0.855-0.885, and the sensitivity and specificity of the model were 0.76 and 0.84, respectively. In an external validation, the AUROC was 0.867 (0.845-0.877). In the survival analysis, delirium occurred more frequently in the group of patients predicted as delirium using an internal validation dataset (p < 0.001). CONCLUSION: Based on machine learning techniques, we analyzed a prediction model of delirium in patients who underwent non-cardiac surgery. Screening for delirium based on the prediction model could improve postoperative care. The working model is provided online and is available for further verification among other populations. TRIAL REGISTRATION: KCT 0006363.
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Delírio do Despertar , Humanos , Masculino , Algoritmos , Área Sob a Curva , Hospitais , Aprendizado de MáquinaRESUMO
Compared to pelubiprofen, a cyclooxygenase-2-selective inhibitor, pelubiprofen tromethamine has been reported to exhibit improved solubility and absorption. Pelubiprofen tromethamine combines the anti-inflammatory effect of pelubiprofen with the gastric protective function of tromethamine salt, making it a relatively safe class of non-steroidal anti-inflammatory drugs with low levels of gastrointestinal side effects in addition to its original analgesic, anti-inflammatory, and antipyretic effects. This study assessed the pharmacokinetic and pharmacodynamic characteristics of pelubiprofen and pelubiprofen tromethamine in healthy subjects. Two independent clinical trials were performed in healthy subjects using a randomized, open-label, oral, single-dose, two-sequence, four-period, crossover design. In Study I and Study II, subjects received 25 mg of pelubiprofen tromethamine and 30 mg of pelubiprofen tromethamine, respectively, with 30 mg of pelubiprofen being the reference. Study I fell within the bioequivalence study criteria. A trend of increased absorption and exposure for 30 mg of pelubiprofen tromethamine vs. the reference in Study II was observed. The maximum cyclooxygenase-2 inhibitory effect of 25 mg of pelubiprofen tromethamine was approximately 98% compared to the reference, showing no significant pharmacodynamic variation. It is thus predicted that 25 mg of pelubiprofen tromethamine would show no clinically significant discrepancies in clinical analgesic and antipyretic effects from 30 mg of pelubiprofen.
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Cardiopulmonary function is exceptionally critical during the early stages of rehabilitation after neurological disorders such as stroke, spinal cord injury and Parkinson's disease. This study aimed to demonstrate how robot-assisted and tilt table exercises affect cardiopulmonary function. In this study, ten healthy young adults performed six combinations of conditions according to robot-assisted mode (on/off), angle of tilt table (20°/60°), and functional electrical stimulation (FES) mode (on/off). Four conditions had FES mode off with combinations of robot-assisted mode (on/off) and tilt angle (20°/60°) and two conditions had robot-assisted mode and FES on with tilt angle (20°/60°). Cardiopulmonary effects (oxygen uptake [VO2], peak oxygen uptake [VO2peak], metabolic energy cost [MET], rate pressure product [RPP], heart rate [HR], maximum heart rate [%HRmax], and minute ventilation [VE]) were compared in each condition. As a result, in the angle and FES mode effect, VO2, VO2peak, MET, RPP, HR, and %HRmax, unlike that for VE, showed major effects in angle. In addition, in the robot-assisted mode and angle effect, when the FES was switched off, VO2, METs, and VE values showed major effects in the robot-assisted mode, whereas all other values showed major effects in angle. Compared to earlier reported findings, we can expect that robot-assisted tilt table training can lead to changes in the cardiopulmonary function.
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The rate of textile waste generation worldwide has increased dramatically due to a rise in clothing consumption and production. Here, conversion of cotton-based, colored cotton-based, and blended cotton-polyethylene terephthalate (PET) textile waste materials into value-added chemicals (bioethanol, sorbitol, lactic acid, terephthalic acid (TPA), and ethylene glycol (EG)) via enzymatic hydrolysis and fermentation was investigated. In order to enhance the efficiency of enzymatic saccharification, effective pretreatment methods for each type of textile waste were developed, respectively. A high glucose yield of 99.1% was obtained from white cotton-based textile waste after NaOH pretreatment. Furthermore, the digestibility of the cellulose in colored cotton-based textile wastes was increased 1.38-1.75 times because of the removal of dye materials by HPAC-NaOH pretreatment. The blended cotton-PET samples showed good hydrolysis efficiency following PET removal via NaOH-ethanol pretreatment, with a glucose yield of 92.49%. The sugar content produced via enzymatic hydrolysis was then converted into key platform chemicals (bioethanol, sorbitol, and lactic acid) via fermentation or hydrogenation. The maximum ethanol yield was achieved with the white T-shirt sample (537 mL/kg substrate), which was 3.2, 2.1, and 2.6 times higher than those obtained with rice straw, pine wood, and oak wood, respectively. Glucose was selectively converted into sorbitol and LA at a yield of 70% and 83.67%, respectively. TPA and EG were produced from blended cotton-PET via NaOH-ethanol pretreatment. The integrated biorefinery process proposed here demonstrates significant potential for valorization of textile waste.
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OBJECTIVE: To investigate the predictors of remission by 4 treatment steps in depressive outpatients receiving 12-week psychopharmacotherapy. METHODS: Patients were consecutively recruited at a university hospital in South Korea from March 2012 to April 2017. At baseline, 1,262 patients were evaluated for sociodemographic and clinical data including assessments scales, and were received antidepressant monotherapy. For patients with an insufficient response or uncomfortable side effects, next treatment steps (1, 2, 3, and 4) with alternative strategies (switching, augmentation, combination, and mixtures of these approaches) were administered considering measurements and patient preference at every 3 weeks in the acute treatment phase (3, 6, 9, and 12 weeks). Remission was defined as a Hamilton Depression Rating Scale score of ≤7. RESULTS: In the multi-variate logistic regression analyses, remission was predicted by higher functional levels in patients received Step 1 and 2 treatment; by lower life stressors in Step 1; by higher social support in Step 3 and 4; and by lower suicidality in Step 1-3. CONCLUSION: Differential associations were found between symptoms or functions and treatment steps, which suggested that multi-faceted evaluations at baseline could predict remission by treatment steps.
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BACKGROUND: Machine-learning techniques are useful for creating prediction models in clinical practice. This study aimed to construct a prediction model of postoperative 30-day mortality based on an automatically extracted electronic preoperative evaluation sheet. METHODS: We used data from 276,341 consecutive adult patients who underwent non-cardiac surgery between January 2011 and December 2020 at a tertiary center for model development and internal validation, and another dataset from 63,384 patients between January 2011 and October 2021 at another center for external validation. Postoperative 30-day mortality was 0.16%. We developed an extreme gradient boosting (XGB) prediction model using only variables from preoperative evaluation sheets. RESULTS: The model yielded an area under the curve of 0.960 and an area under the precision and recall curve of 0.216, which were 0.932 and 0.122, respectively, in the external validation set. The optimal threshold calculated by Youden's J statistic had a sensitivity of 0.885 and specificity of 0.914. In an additional analysis with balanced distribution, the model showed a similar predictive value. CONCLUSION: We presented a machine-learning prediction model for 30-day mortality after non-cardiac surgery using preoperative variables automatically extracted from electronic medical records and validated the model in a multi-center setting. Our model may help clinicians predict postoperative outcomes.
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As the CNS-resident macrophages and member of the myeloid lineage, microglia fulfill manifold functions important for brain development and homeostasis. In the context of neurodegenerative diseases, they have been implicated in degenerative and regenerative processes. The discovery of distinct activation patterns, including increased phagocytosis, indicated a damaging role of myeloid cells in multiple system atrophy (MSA), a devastating, rapidly progressing atypical parkinsonian disorder. Here, we analyzed the gene expression profile of microglia in a mouse model of MSA (MBP29-hα-syn) and identified a disease-associated expression profile and upregulation of the colony-stimulating factor 1 (Csf1). Thus, we hypothesized that CSF1 receptor-mediated depletion of myeloid cells using PLX5622 modifies the disease progression and neuropathological phenotype in this mouse model. Intriguingly, sex-balanced analysis of myeloid cell depletion in MBP29-hα-syn mice revealed a two-faced outcome comprising an improved survival rate accompanied by a delayed onset of neurological symptoms in contrast to severely impaired motor functions. Furthermore, PLX5622 reversed gene expression profiles related to myeloid cell activation but reduced gene expression associated with transsynaptic signaling and signal release. While transcriptional changes were accompanied by a reduction of dopaminergic neurons in the SNpc, striatal neuritic density was increased upon myeloid cell depletion in MBP29-hα-syn mice. Together, our findings provide insight into the complex, two-faced role of myeloid cells in the context of MSA emphasizing the importance to carefully balance the beneficial and adverse effects of CSF1R inhibition in different models of neurodegenerative disorders before its clinical translation.SIGNIFICANCE STATEMENT Myeloid cells have been implicated as detrimental in the disease pathogenesis of multiple system atrophy. However, long-term CSF1R-dependent depletion of these cells in a mouse model of multiple system atrophy demonstrates a two-faced effect involving an improved survival associated with a delayed onset of disease and reduced inflammation which was contrasted by severely impaired motor functions, synaptic signaling, and neuronal circuitries. Thus, this study unraveled a complex role of myeloid cells in multiple system atrophy, which indicates important functions beyond the previously described disease-associated, destructive phenotype and emphasized the need of further investigation to carefully and individually fine-tune immunologic processes in different neurodegenerative diseases.
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Atrofia de Múltiplos Sistemas , Animais , Camundongos , Atrofia de Múltiplos Sistemas/genética , Longevidade , Compostos Orgânicos/farmacologia , Microglia/metabolismo , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/metabolismo , Modelos Animais de Doenças , Células Mieloides/metabolismo , Receptores de Fator Estimulador de ColôniasRESUMO
There are no studies evaluating the effect of left paratracheal pressure (PP) on difficulty of intubation using Pentax Airway Scope (Pentax), so we conducted this study to show that PP was not inferior to cricoid pressure (CP) in intubation time using the Pentax. Patients aged 19-70 years, with an American Society of Anesthesiologists physical status 1 or 2, and undergoing otorhinolaryngological, gynecological surgery, and cholecystectomy at a single university hospital were enrolled. Intubation was performed using the Pentax under PP or CP of 30 N. The primary outcome was intubation time, and the secondary outcomes were tube advancement difficulty and glottis view. The mean difference in intubation time (PP group - CP group) was - 4.19 s (95% CI - 8.24 to - 0.15), which was within the non-inferiority margin of 6.5 s, thus proving non-inferiority of the PP compared with the CP group. However, the score for tube advancement difficulty was significantly lower in the PP group than in the CP group (p = 0.02). PP did not prolong the intubation time and showed comparable intubation conditions to CP in intubation using the Pentax. Therefore, PP may be a good alternative maneuver to prevent gastric regurgitation during intubation using the Pentax.
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Laringoscópios , Glote , Humanos , Intubação Intratraqueal , Laringoscopia , Sistema RespiratórioRESUMO
The pulse CO-Oximetry allows continuous, noninvasive monitoring of hemoglobin (SpHb). We assessed the impact of increased end-tidal carbon dioxide (EtCO2) on the accuracy and trending ability of SpHb in laparoscopic surgery. Participants (n = 64) were randomly allocated to the low carbon dioxide (CO2) group (EtCO2: 30-35 mmHg) or the high CO2 group (EtCO2: 40-45 mmHg). The SpHb and laboratory hemoglobin (tHb) were obtained during surgery. The correlation coefficient (r) between SpHb and tHb showed greater tendency in the low CO2 group (r = 0.68) than in the high CO2 group (r = 0.43). The bias (precision) was -1.18 (1.09) with a limit of agreement (LOA) of -3.31 to 0.95 in low CO2 group and -1.02 (1.24) with a LOA of -3.45 to 1.42 in high CO2 group; they did not differ significantly between the groups (p = 0.246). The low CO2 group showed a high concordance rate of 95.9% and a moderate correlation between ΔSpHb and ΔtHb (r = 0.53). However, the high CO2 group showed a concordance rate of 77.8% and no correlation between ΔSpHb and ΔtHb (r = 0.11). In conclusion, increased EtCO2 significantly reduced the trending ability of SpHb during laparoscopic surgery. Caution should be executed when interpreting SpHb values during laparoscopic surgery in patients with hypercapnia.
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BACKGROUND: Postreperfusion syndrome (PRS) is a serious complication that can occur during liver transplantation (LT) and is known to affect morbidity and mortality after surgery. However, PRS definition does not include which artery is used to measure blood pressure. Until now, various studies have reported on the incidence, prognosis, and prevention strategies of PRS, but the arterial pressure used in these studies shows heterogeneity. Moreover, femoral arterial pressure and radial arterial pressure show a significant difference especially immediately after reperfusion. To the best of our knowledge there was no study about the comparison of the incidence of PRS according to artery. Therefore, in this study, we would like to investigate if there is a difference in the incidence of PRS between the radial and femoral artery. METHODS: With approval of IRB, we retrospectively reviewed medical records of adult LT patients from April 2017 to April 2019. We reviewed each patient's anesthesia record and confirmed if PRS has occurred. RESULTS: A total of 251 patients were enrolled. The PRS was measured in radial artery from 84 patients (33.5%) and femoral artery from 71 patients (28.3%). McNemar's test was performed and there was a significant difference (P value .007). CONCLUSIONS: This study confirmed that radial artery had higher incidence of PRS than femoral artery. However, it was not confirmed if PRS measurement at any artery is appropriate for predicting morbidity and mortality after surgery. Therefore, in the future, it is better to conduct research based on arteries that predict the prognosis better.