RUNX1-deficient human megakaryocytes demonstrate thrombopoietic and platelet half-life and functional defects.

Heterozygous defects in runt-related transcription factor 1 (RUNX1) are causative of a familial platelet disorder with associated myeloid malignancy (FPDMM). Because RUNX1-deficient animal models do not mimic bleeding disorder or leukemic risk associated with FPDMM, development of a proper model system is critical to understanding the underlying mechanisms of the observed phenotype and to identifying therapeutic interventions. We previously reported an in vitro megakaryopoiesis system comprising human CD34+ hematopoietic stem and progenitor cells that recapitulated the FPDMM quantitative megakaryocyte defect through a decrease in RUNX1 expression via a lentiviral short hairpin RNA strategy. We now show that shRX-megakaryocytes have a marked reduction in agonist responsiveness. We then infused shRX-megakaryocytes into immunocompromised NOD scid gamma (NSG) mice and demonstrated that these megakaryocytes released fewer platelets than megakaryocytes transfected with a nontargeting shRNA, and these platelets had a diminished half-life. The platelets were also poorly responsive to agonists, unable to correct thrombus formation in NSG mice homozygous for a R1326H mutation in von Willebrand Factor (VWFR1326H), which switches the species-binding specificity of the VWF from mouse to human glycoprotein Ibα. A small-molecule inhibitor RepSox, which blocks the transforming growth factor ß1 (TGFß1) pathway and rescued defective megakaryopoiesis in vitro, corrected the thrombopoietic defect, defects in thrombus formation and platelet half-life, and agonist response in NSG/VWFR1326H mice. Thus, this model recapitulates the defects in FPDMM megakaryocytes and platelets, identifies previously unrecognized defects in thrombopoiesis and platelet half-life, and demonstrates for the first time, reversal of RUNX1 deficiency-induced hemostatic defects by a drug.

A new G-quadruplex-specific photosensitizer inducing genome instability in cancer cells by triggering oxidative DNA damage and impeding replication fork progression.

Photodynamic therapy (PDT) ideally relies on the administration, selective accumulation and photoactivation of a photosensitizer (PS) into diseased tissues. In this context, we report a new heavy-atom-free fluorescent G-quadruplex (G4) DNA-binding PS, named DBI. We reveal by fluorescence microscopy that DBI preferentially localizes in intraluminal vesicles (ILVs), precursors of exosomes, which are key components of cancer cell proliferation. Moreover, purified exosomal DNA was recognized by a G4-specific antibody, thus highlighting the presence of such G4-forming sequences in the vesicles. Despite the absence of fluorescence signal from DBI in nuclei, light-irradiated DBI-treated cells generated reactive oxygen species (ROS), triggering a 3-fold increase of nuclear G4 foci, slowing fork progression and elevated levels of both DNA base damage, 8-oxoguanine, and double-stranded DNA breaks. Consequently, DBI was found to exert significant phototoxic effects (at nanomolar scale) toward cancer cell lines and tumor organoids. Furthermore, in vivo testing reveals that photoactivation of DBI induces not only G4 formation and DNA damage but also apoptosis in zebrafish, specifically in the area where DBI had accumulated. Collectively, this approach shows significant promise for image-guided PDT.

Local Heating Induced Single-Crystalline Phase Control in Electrochemical Synthesis of Nanomaterials.

Development of synthetic strategies selectively yielding single crystals is desired owing to the facet-dependent chemical reactivities. Recent advances in electrochemical materials synthesis yielded nanomaterials that are surfactant-free, however, typically in polycrystalline forms. In this work, an electrochemical synthetic strategy selectively yielding single-crystalline nanoparticles by implementation of surface-selective heating of the working electrode is developed. Single crystals of copper, silver, gold, and platinum are afforded, and the crystallinity verified by electron diffraction and chemical reactivity studies. Notably, Cu (100) surface prepared by electrochemical synthesis yielded high single product selectivity when applied to electrochemical CO2 reduction catalysis.

Driving Triplet State Population in Benzothioxanthene Imide Dyes: Let's twist!

Controlling the formation of photoexcited triplet states is critical for many (photo)chemical and physical applications. Here, we demonstrate that a permanent out-of-plane distortion of the benzothioxanthene imide (BTI) dye promotes intersystem crossing by increasing spin-orbit coupling. This manipulation was achieved through a subtle chemical modification, specifically the bay-area methylation. Consequently, this simple yet efficient approach expands the catalog of known molecular engineering strategies for synthesizing heavy atom-free, dual redox-active, yet still emissive and synthetically accessible photosensitizers.

Association of Mechanical Energy and Power with Postoperative Pulmonary Complications in Lung Resection Surgery: A Post Hoc Analysis of Randomized Clinical Trial Data.

BACKGROUND: Mechanical power (MP), the rate of mechanical energy (ME) delivery, is a recently introduced unifying ventilator parameter consisting of tidal volume, airway pressures, and respiratory rates, which predicts pulmonary complications in several clinical contexts. However, ME has not been previously studied in the perioperative context, and neither parameter has been studied in the context of thoracic surgery utilizing one-lung ventilation. METHODS: The relationships between ME variables and postoperative pulmonary complications were evaluated in this post hoc analysis of data from a multicenter randomized clinical trial of lung resection surgery conducted between 2020 and 2021 (n = 1,170). Time-weighted average MP and ME (the area under the MP time curve) were obtained for individual patients. The primary analysis was the association of time-weighted average MP and ME with pulmonary complications within 7 postoperative days. Multivariable logistic regression was performed to examine the relationships between energy variables and the primary outcome. RESULTS: In 1,055 patients analyzed, pulmonary complications occurred in 41% (431 of 1,055). The median (interquartile ranges) ME and time-weighted average MP in patients who developed postoperative pulmonary complications versus those who did not were 1,146 (811 to 1,530) J versus 924 (730 to 1,240) J (P < 0.001), and 6.9 (5.5 to 8.7) J/min versus 6.7 (5.2 to 8.5) J/min (P = 0.091), respectively. ME was independently associated with postoperative pulmonary complications (ORadjusted, 1.44 [95% CI, 1.16 to 1.80]; P = 0.001). However, the association between time-weighted average MP and postoperative pulmonary complications was time-dependent, and time-weighted average MP was significantly associated with postoperative pulmonary complications in cases utilizing longer periods of mechanical ventilation (210 min or greater; ORadjusted, 1.46 [95% CI, 1.11 to 1.93]; P = 0.007). Normalization of ME and time-weighted average MP either to predicted body weight or to respiratory system compliance did not alter these associations. CONCLUSIONS: ME and, in cases requiring longer periods of mechanical ventilation, MP were independently associated with postoperative pulmonary complications in thoracic surgery.

Association between body mass index and results of cryoballoon ablation in Korean patients with atrial fibrillation: an analysis from the Korean Heart Rhythm Society Cryoablation registry.

AIMS: Pulmonary vein isolation using cryoablation is effective and safe in patients with atrial fibrillation (AF). Although both obesity and underweight are associated with a higher risk for incident AF, there is limited data on the efficacy and safety following cryoablation according to body mass index (BMI) especially in Asians. METHODS AND RESULTS: Using the Korean Heart Rhythm Society Cryoablation registry, a multicentre registry of 12 tertiary hospitals, we analysed AF recurrence and procedure-related complications after cryoablation by BMI (kg/m2) groups (BMI < 18.5, underweight, UW; 18.5-23, normal, NW; 23-25, overweight, OW; 25-30, obese Ⅰ, OⅠ; ≥30, obese Ⅱ, OⅡ). A total of 2648 patients were included (median age 62.0 years; 76.7% men; 55.6% non-paroxysmal AF). Patients were categorized by BMI groups: 0.9% UW, 18.7% NW, 24.8% OW, 46.1% OI, and 9.4% OII. Underweight patients were the oldest and had least percentage of non-paroxysmal AF (33.3%). During a median follow-up of 1.7 years, atrial arrhythmia recurred in 874 (33.0%) patients (incidence rate, 18.9 per 100 person-years). After multivariable adjustment, the risk of AF recurrence was higher in UW group compared with NW group (adjusted hazard ratio, 95% confidence interval; 2.55, 1.18-5.50, P = 0.02). Procedure-related complications occurred in 123 (4.7%) patients, and the risk was higher for UW patients (odds ratio, 95% confidence interval; 2.90, 0.94-8.99, P = 0.07), mainly due to transient phrenic nerve palsy. CONCLUSION: Underweight patients showed a higher risk of AF recurrence after cryoablation compared with NW patients. Also, careful attention is needed on the occurrence of phrenic nerve palsy in UW patients.

Association of Argatroban Dose With Coagulation Laboratory Test in Patients on Extracorporeal Membrane Oxygenation: Activated Clotting Time vs Activated Partial Thromboplastin Time.

BACKGROUND: Only some studies have directly compared and analyzed the roles of activated partial thromboplastin time (aPTT) and activated clotting time (ACT) in coagulation monitoring during argatroban administration. OBJECTIVES: This study aims to assess the correlation of argatroban dose with ACT and aPTT values and to identify the optimal coagulation test for argatroban dose adjustment. METHODS: We evaluated 55 patients on extracorporeal membrane oxygenation (ECMO) who received argatroban for more than 72 hours. The correlation between argatroban dose and aPTT and ACT values was evaluated. To compare argatroban dose and bleeding events according to liver dysfunction, the patients were divided into 2 groups based on alanine aminotransferase and total bilirubin. RESULTS: Among the 55 patients, a total of 459 doses and coagulation tests were evaluated. The aPTT and ACT values showed a weak correlation with argatroban dose, with the Pearson correlation coefficients of 0.261 (P < 0.001) and 0.194 (P = 0.001), respectively. The agreement between the target 150 to 180 seconds for ACT and 55 to 75 seconds for aPTT was observed in 140 patients (46.1%). Twenty-four patients (43.6%) had liver dysfunction when they started argatroban. The median argatroban dose was lower in the liver dysfunction group than in the control group (0.094 mcg/kg/min vs 0.169 mcg/kg/min, P = 0.020). Difference was not observed between the 2 groups in the amount of red blood cell (0.47 vs 0.43 pack, P = 0.909) and platelet (0.60 vs 0.08 pack, P = 0.079) transfusion per day. CONCLUSION AND RELEVANCE: A weak correlation was observed between argatroban dose and the aPTT and ACT values. However, the agreement between aPTT and ACT was only 46.1% regarding the scope of target range. Further research is necessary to determine how to assess the optimal argatroban dose for patients administered argatroban while undergoing ECMO at the intensive care unit.

Effect of Sevoflurane Anesthesia on Diastolic Function: A Prospective Observational Study.

BACKGROUND: The effect of sevoflurane on left ventricular diastolic function is not well understood. We hypothesized that parameters of diastolic function may improve under sevoflurane anesthesia in patients with preexisting diastolic dysfunction compared to patients with normal diastolic function. METHODS: This observational study included 60 patients undergoing breast surgery or laparoscopic cholecystectomy. Patients were assigned to diastolic dysfunction (n = 34) or normal (n = 26) groups of septal e' < 8 or ≥ 8.0 cm/s on the first thoracic echocardiography (TTE) performed before anesthesia. During anesthesia, sevoflurane was maintained at 1 to 2 minimum alveolar concentration (MAC) to maintain the bispectral index at 40 to 50. At the end of surgery, the second TTE was performed under 0.8 to 1 MAC of sevoflurane with the patient breathing spontaneously without ventilator support. Primary end point was the percentage change (Δ) of e' on 2 TTEs (Δe'). Secondary end points were ΔE/e', Δleft atrial volume index (ΔLAVI), and Δtricuspid regurgitation maximum velocity (ΔTR Vmax). These percentage changes (Δ) were compared between diastolic dysfunction and normal groups. RESULTS: e' (Δe': 30 [6, 64] vs 0 [-18, 11]%; P < .001), mitral inflow E wave velocity (E), mitral inflow E/A ratio (E/A), and mitral E velocity deceleration time (DT) improved significantly in diastolic dysfunction group compared to normal group. LAVI decreased in diastolic dysfunction group but did not reach statistical significance between the 2 groups (ΔLAVI:-15 [-31, -3] vs -4 [-20, 10]%, P = .091). ΔE/e' was not different between the 2 groups (11 [-16, 26] vs 12 [-9, 22]%, P = .853) (all: median [interquartile range, IQR]). TR was minimal in both groups. CONCLUSIONS: In this study, echocardiographic parameters of diastolic function, including septal e', E, E/A, and DT, improved with sevoflurane anesthesia in patients with preexisting diastolic dysfunction, but remained unchanged in patients with normal diastolic function.

Comparison of tracheal versus esophageal temperatures during laparoscopic surgery.

PURPOSE: Recently, endotracheal tubes with an embedded temperature sensor in the inner surface of the tube cuff (temperature tracheal tubes) have been developed. We sought to assess whether temperature tracheal tubes show a good agreement with esophageal temperature probes during surgery. METHODS: We enrolled 40 patients who underwent laparoscopic surgery in an observational study. The tracheas of all patients were intubated with a temperature tracheal tube, and an esophageal temperature probe was inserted into the esophagus. Tracheal and esophageal temperatures were recorded at 15-min intervals until the end of surgery. Temperatures from both devices were analyzed using Bland-Altman analysis, four-quadrant plots, and polar plots. RESULTS: We analyzed 261 data points from 36 patients. Temperatures ranges were 34.2 °C to 36.6 °C for the tracheal temperature tube and 34.7 °C to 37.2 °C for the esophageal temperature probe. Bland-Altman analysis showed an acceptable agreement between the two devices, with an overall mean bias (95% limit of agreement) of -0.3 °C (-0.8 °C to 0.1 °C) and a percentage error of 3%; the trending ability (temperature changes over time) between the two devices showed a concordance rate of 94% in four-quadrant plot (cut-off ≥ 92%), but this was higher than the acceptable mean angular bias of 177° (cut-off < ± 5°) and radial limits of agreement of 52° (cut-off < ± 30°) in the polar plot. Bronchoscopy during extubation and patient interviews at six hours postoperatively revealed no serious injuries related to the use of the temperature tracheal tube. CONCLUSION: The temperature tracheal tube showed an acceptable overall mean bias of -0.3 °C and a percentage error of 3%, but incompatible trending ability with the esophageal temperature probe. STUDY REGISTRATION: cris.nih.go.kr (KCT0007265); 22 April 2022.

RéSUMé: OBJECTIF: Récemment, des sondes endotrachéales munies d'un capteur de température intégré dans la surface interne du ballonnet de la sonde (sondes thermiques trachéales) ont été mises au point. Nous avons cherché à évaluer si les sondes trachéales de température montraient une bonne concordance avec les sondes thermiques œsophagiennes pendant la chirurgie. MéTHODE: Nous avons recruté 40 patient·es ayant bénéficié d'une chirurgie par laparoscopie dans le cadre d'une étude observationnelle. Les trachées de tou·tes les patient·es ont été intubées à l'aide d'une sonde trachéale de température et une sonde thermique œsophagienne a été insérée dans l'œsophage. Les températures trachéale et œsophagienne ont été enregistrées à des intervalles de 15 minutes jusqu'à la fin de la chirurgie. Les températures des deux appareils ont été analysées à l'aide d'une analyse de Bland-Altman, de diagrammes à quatre quadrants et de diagrammes polaires. RéSULTATS: Nous avons analysé 261 points de données provenant de 36 patient·es. Les plages de température allaient de 34,2 °C à 36,6 °C pour la sonde trachéale de température et de 34,7 °C à 37,2 °C pour la sonde thermique œsophagienne. L'analyse de Bland-Altman a montré une concordance acceptable entre les deux dispositifs, avec un biais moyen global (limite de 95 % de la concordance) de −0,3 °C (−0,8 °C à 0,1 °C) et un pourcentage d'erreur de 3 %; la capacité de tendance (changements de température au fil du temps) entre les deux dispositifs a montré un taux de concordance de 94 % dans un diagramme à quatre quadrants (limite ≥ 92 %), mais cette capacité était plus élevée que le biais angulaire moyen acceptable de 177° (limite < ± 5°) et que les limites radiales de l'accord de 52° (limite < ± 30°) dans le diagramme polaire. La bronchoscopie réalisée lors de l'extubation et les entretiens avec les patient·es six heures après l'opération n'ont révélé aucune blessure grave liée à l'utilisation de la sonde trachéale de température. CONCLUSION: La sonde trachéale de température a montré un biais moyen global acceptable de −0,3 °C et un pourcentage d'erreur de 3 %, mais une capacité de tendance incompatible avec la sonde thermique œsophagienne. ENREGISTREMENT DE L'éTUDE: cris.nih.go.kr (KCT0007265); 22 avril 2022.

Comparison of high-flow nasal cannula and conventional nasal cannula during deep sedation for endoscopic submucosal dissection: a randomized controlled trial.

PURPOSE: Adequate oxygenation and airway management during deep sedation can be challenging. We investigated the effect of high-flow nasal cannula (group HF) and conventional nasal cannula (group CO) during sedation for endoscopic submucosal dissection (ESD). METHODS: Patients undergoing ESD with deep sedation were enrolled. The primary outcome was difference in lowest oxygen saturation (SpO2) between the groups. Incidence of hypoxia (SpO2 < 90%), patients with SpO2 < 95%, hypercapnia, and airway interventions; operator satisfaction; and adverse events were recorded. RESULTS: Thirty-two patients in each group completed the study. The mean of minimum SpO2 values was significantly higher in group HF than in group CO (96.8% ± 4.2% vs. 93.3% ± 5.3%, p = 0.005). The incidence of hypoxia was comparable between the groups (4 [12.5%] vs. 6 [18.8%], p = 0.491); however, patients with SpO2 < 95% were significantly less in group HF (5 [15.6%] vs. 18 [56.3%], p = 0.003). Incidence of hypercapnia was higher in group HF than in group CO (14 [46.7%] vs. 5 [16.7%], p = 0.013). Airway rescue interventions were significantly less common in group HF. Satisfaction of operators and post-procedural complications were comparable between the two groups. In multivariable analysis, group CO and higher body mass index were risk factors for airway managements (odds ratio [95% confidence interval]: 6.204 [1.784-21.575], p = 0.004; 1.337 [1.043-1.715], p = 0.022, respectively). CONCLUSIONS: Compared to conventional nasal cannula, high-flow nasal cannula maintained higher minimum SpO2 value during deep sedation with propofol-remifentanil for ESD. TRIAL REGISTRATION: Clinical Trial Registry of the Republic of Korea (KCT0006618, https://cris.nih.go.kr ; registered September 29, 2021; principal investigator: Ji Won Choi).

Analysing the impact of body position shift on sleep architecture and stage transition: A comprehensive multidimensional study using event-synchronised polysomnography data.

Although understanding the physiological mechanisms of obstructive sleep apnea (OSA) is important for treating OSA, limited studies have examined OSA patients' sleep architecture at the epoch-by-epoch level and analysed the impact of sleep position and stage on OSA pathogenesis. The epoch-labelled polysomnogram was analysed multidimensionally to investigate the effect of sleep position on the sleep architecture and risk factors of apnea in patients with OSA. This retrospective multicentric case-control study reviewed full-night diagnostic polysomnography of 6983 participants. The difference in the proportion of time spent supine during non-rapid eye movement (NREM) and REM stages, and the mean duration of respiratory events per body position were evaluated. The frequency of sleep stage transition per body position shift type was computed. Further subgroup analysis was performed based on OSA severity and positional dependency. Supine time in patients with OSA varied across sleep stages, with lower proportions in N3 and REM, and shorter durations with severity. Patients with OSA spent less time in supine positions during N3 and REM, and experienced longer apnea events in both positions compared to the control group. The frequency of all sleep stage transitions increased with OSA severity and was higher among non-positional OSA than positional OSA and the control group, regardless of body position shift type. The sleep stage transition from N3 and REM to wakefulness was notably heightened during position shift. Understanding the sleep architecture of patients with OSA requires analysing various sleep characteristics including sleep position simultaneously, with future studies focusing on position detection to predict sleep stages and respiratory events.

Improvement in current drivability and stability in nanoscale vertical channel thin-film transistors via band-gap engineering in In-Ga-Zn-O bilayer channel configuration.

Vertical channel thin film transistors (VTFTs) have been expected to be exploited as one of the promising three-dimensional devices demanding a higher integration density owing to their structural advantages such as small device footprints. However, the VTFTs have suffered from the back-channel effects induced by the pattering process of vertical sidewalls, which critically deteriorate the device reliability. Therefore, to reduce the detrimental back-channel effects has been one of the most urgent issues for enhancing the device performance of VTFTs. Here we show a novel strategy to introduce an In-Ga-Zn-O (IGZO) bilayer channel configuration, which was prepared by atomic-layer deposition (ALD), in terms of structural and electrical passivation against the back-channel effects. Two-dimensional electron gas was effectively employed for improving the operational reliability of the VTFTs by inducing strong confinement of conduction electrons at heterojunction interfaces. The IGZO bilayer channel structure was composed of 3 nm-thick In-rich prompt (In/Ga = 4.1) and 12 nm-thick prime (In/Ga = 0.7) layers. The VTFTs using bilayer IGZO channel showed high on/off ratio (4.8 × 109), low SS value (180 mV dec-1), and high current drivability (13.6µAµm-1). Interestingly, the strategic employment of bilayer channel configurations has secured excellent device operational stability representing the immunity against the bias-dependent hysteretic drain current and the threshold voltage instability of the fabricated VTFTs. Moreover, the threshold voltage shifts of the VTFTs could be suppressed from +5.3 to +2.6 V under a gate bias stress of +3 MV cm-1for 104s at 60 °C, when the single layer channel was replaced with the bilayer channel. As a result, ALD IGZO bilayer configuration could be suggested as a useful strategy to improve the device characteristics and operational reliability of VTFTs.

Driving pressure-guided ventilation and postoperative pulmonary complications in thoracic surgery: a multicentre randomised clinical trial.

BACKGROUND: Airway driving pressure, easily measured as plateau pressure minus PEEP, is a surrogate for alveolar stress and strain. However, the effect of its targeted reduction remains unclear. METHODS: In this multicentre trial, patients undergoing lung resection surgery were randomised to either a driving pressure group (n=650) receiving an alveolar recruitment/individualised PEEP to deliver the lowest driving pressure or to a conventional protective ventilation group (n=650) with fixed PEEP of 5 cm H2O. The primary outcome was a composite of pulmonary complications within 7 days postoperatively. RESULTS: The modified intention-to-treat analysis included 1170 patients (mean [standard deviation, sd]; age, 63 [10] yr; 47% female). The mean driving pressure was 7.1 cm H2O in the driving pressure group vs 9.2 cm H2O in the protective ventilation group (mean difference [95% confidence interval, CI]; -2.1 [-2.4 to -1.9] cm H2O; P<0.001). The incidence of pulmonary complications was not different between the two groups: driving pressure group (233/576, 40.5%) vs protective ventilation group (254/594, 42.8%) (risk difference -2.3%; 95% CI, -8.0% to 3.3%; P=0.42). Intraoperatively, lung compliance (mean [sd], 42.7 [12.4] vs 33.5 [11.1] ml cm H2O-1; P<0.001) and Pao2 (median [inter-quartile range], 21.5 [14.5 to 30.4] vs 19.5 [13.5 to 29.1] kPa; P=0.03) were higher and the need for rescue ventilation was less frequent (6.8% vs 10.8%; P=0.02) in the driving pressure group. CONCLUSIONS: In lung resection surgery, a driving pressure-guided ventilation improved pulmonary mechanics intraoperatively, but did not reduce the incidence of postoperative pulmonary complications compared with a conventional protective ventilation. CLINICAL TRIAL REGISTRATION: NCT04260451.

Enhanced Recovery After Surgery Program and Opioid Consumption in Pulmonary Resection Surgery: A Retrospective Observational Study.

BACKGROUND: Pulmonary resection surgery causes severe postoperative pain and usually requires opioid-based analgesia, particularly in the early postoperative period. However, the administration of large amounts of opioids is associated with various adverse events. We hypothesized that patients who underwent pulmonary resection under an enhanced recovery after surgery (ERAS) program consumed fewer opioids than patients who received conventional treatment. METHODS: A total of 2147 patients underwent pulmonary resection surgery between August 2019 and December 2020. Two surgeons (25%) at our institution implemented the ERAS program for their patients. After screening, the patients were divided into the ERAS and conventional groups based on the treatment they received. The 2 groups were then compared after the stabilized inverse probability of treatment weighting. The primary end point was the total amount of opioid consumption from surgery to discharge. The secondary end points included daily average and highest pain intensity scores during exertion, opioid-related adverse events, and clinical outcomes, such as length of intensive care unit (ICU) stay, hospital stay, and postoperative complication grade defined by the Clavien-Dindo classification. Additionally, the number of patients discharged without opioids prescription was assessed. RESULTS: Finally, 2120 patients were included in the analysis. The total amount of opioid consumption (median [interquartile range]) after surgery until discharge was lower in the ERAS group (n = 260) than that in the conventional group (n = 1860; morphine milligram equivalents, 44 [16-122] mg vs 208 [146-294] mg; median difference, -143 mg; 95% CI, -154 to -132; P < .001). The number of patients discharged without opioids prescription was higher in the ERAS group (156/260 [60%] vs 329/1860 [18%]; odds ratio, 7.0; 95% CI, 5.3-9.3; P < .001). On operation day, both average pain intensity score during exertion (3.0 ± 1.7 vs 3.5 ± 1.8; mean difference, -0.5; 95% CI, -0.8 to -0.3; P < .001) and the highest pain intensity score during exertion (5.5 ± 2.1 vs 6.4 ± 1.7; mean difference, -0.8; 95% CI, -1.0 to -0.5; P < .001) were lower in the ERAS group than in the conventional group. There were no significant differences in the length of ICU stay, hospital stay, or Clavien-Dindo classification grade. CONCLUSIONS: Patients who underwent pulmonary resection under the ERAS program consumed fewer opioids than those who received conventional management while maintaining no significant differences in clinical outcomes.

Euscaphic acid relieves fatigue by enhancing anti-oxidative and anti-inflammatory effects.

BACKGROUND: Oxidative stress and inflammation are involved in chronic fatigue. Euscaphic acid (EA) is an active compound of Eriobotrya japonica (Loquat) and has anti-oxidative effect. METHODS: The goal of present study is to prove whether EA could relieve fatigue through enhancing anti-oxidant and anti-inflammatory effects in in vitro/in vivo models. RESULTS: EA notably improved activity of superoxide dismutase (SOD) and catalase (CAT), while EA reduced levels of malondiadehyde (MDA) and inflammatory cytokines without cytotoxicity in H2O2-stimulated in myoblast cell line, C2C12 cells. EA significantly reduced levels of fatigue-causing factors such as lactate dehydrogenase (LDH) and creatin kinase (CK), while EA significantly incresed levels of anti-fatigue-related factor, glycogen compared to the H2O2-stimulated C2C12 cells. In treadmill stress test (TST), EA significantly enhanced activities of SOD and CAT as well as exhaustive time and decreased levels of MDA and inflammatory cytokines. After TST, levels of free fatty acid, citrate synthase, and muscle glycogen were notably enhanced by oral administration of EA, but EA decreased levels of lactate, LDH, cortisol, aspartate aminotransferase, alanine transaminase, CK, glucose, and blood urea nitrogen compared to the control group. Furthermore, in forced swimming test, EA significantly increased levels of anti-fatigue-related factors and decreased excessive accumulations of fatigue-causing factors. CONCLUSIONS: Therefore, the results indicate that potent anti-fatigue effect of EA can be achieved via the improvement of anti-oxidative and anti-inflammatory properties, and this study will provide scientific data for EA to be developed as a novel and efficient component in anti-fatigue health functional food.

Dual-Dewetting Process for Self-Assembled Nanoparticle Clusters in Wafer Scale.

Plasmonic molecules, which are geometrically well-defined plasmonic metal nanoparticle clusters, have attracted significant attention due to their enhancement of light-matter interactions owing to a stronger electric field enhancement than that by single particles. High-resolution lithography techniques provide precise positioning of plasmonic nanoparticles, but their fabrication costs are excessively high. In this study, we propose a lithography-free, self-assembly fabrication method, termed the dual-dewetting process, which allows the control of the size and density of gold nanoparticles. This process involves depositing a gold thin film on a substrate and inducing dewetting through thermal annealing, followed by a second deposition and annealing. The method achieves a uniform distribution of particle size and density, along with increased particle density, across a 6-inch wafer. The superiority of the method is confirmed by a 30-fold increase in the signal intensity of surface-enhanced Raman scattering following the additional dewetting with an 8 nm film, compared to single dewetting alone. Our findings indicate that the dual-dewetting method provides a simple and efficient approach to enable a variety of plasmonic applications through efficient plasmonic molecule large-area fabrication.

Time from Exposure to Diagnosis among Quarantined Close Contacts of SARS-CoV-2 Omicron Variant Index Case-Patients, South Korea.

To determine optimal quarantine duration, we evaluated time from exposure to diagnosis for 107 close contacts of severe acute respiratory syndrome coronavirus 2 Omicron variant case-patients. Average time from exposure to diagnosis was 3.7 days; 70% of diagnoses were made on day 5 and 99.1% by day 10, suggesting 10-day quarantine.

Community Transmission of SARS-CoV-2 Omicron Variant, South Korea, 2021.

In South Korea, a November 2021 outbreak caused by severe acute respiratory syndrome coronavirus 2 Omicron variant originated from 1 person with an imported case and spread to households, kindergartens, workplaces, restaurants, and hospitals, resulting in 11 clusters within 3 weeks. An epidemiologic curve indicated rapid community transmission of the Omicron variant.

Membraneless Ionic Liquid Droplet Nanoprobe for Oxygen Sensing and Gas Phase Scanning Electrochemical Microscopy.

A novel membraneless oxygen sensing nanoprobe was developed based on a hanging drop ionic liquid electrochemical cell. An ultrasmall (<500 nm) working electrode and small volume electrochemical cell allowed for an impressively low detection limit of ∼13 ppm and a response time less than 100 ms, which is unusually fast for an electrochemical gas sensor. The oxygen sensor was stable for hours of operation and, owing to the membraneless design, was easily regenerable when fouled. The pulled capillary form factor of the nanoprobe was found compatible with scanning probe techniques, the demonstration of which was made by application as a tip electrode in gas phase scanning electrochemical microscopy (SECM). In the SECM experiments, the oxygen nanoprobe exhibited micrometer scale spatial resolution with ease. This unique probe design developed here may potentially be engineered into versatile sensors for various volatile molecules other than oxygen, such as those pertinent to hazard analysis and biomedical diagnosis.

Measuring glomerular blood transfer rate in kidney using diffusion-weighted arterial spin labeling.

PURPOSE: To propose a two-compartment renal perfusion model for calculating glomerular blood transfer rate ( k G $$ {k}_G $$ ) as a new measure of renal function. THEORY: The renal perfusion signal was divided into preglomerular and postglomerular flows according to flow velocity. By analyzing perfusion signals acquired with and without diffusion gradients, we estimated k G $$ {k}_G $$ , the blood transfer rate from the afferent arterioles into the glomerulus. METHODS: A multislice multidelay diffusion-weighted arterial spin labeling sequence was applied to subjects with no history of renal dysfunctions. In the multiple b-value experiment, images were acquired with seven b-values to validate the bi-exponential decays of the renal perfusion signal and to determine the appropriate b-value for suppressing preglomerular flow. In the caffeine challenge, six subjects were scanned twice on the caffeine day and the control day. The k G $$ {k}_G $$ values of the two dates were compared. RESULTS: The perfusion signal showed a bi-exponential decay with b-values. There was no significant difference in renal blood flow and arterial transit time between caffeine and control days. In contrast, cortical k G $$ {k}_G $$ was significantly higher on the caffeine day (caffeine day: 106 . 0 ± 20 . 3 $$ 106.0\pm 20.3 $$ min - 1 $$ {}^{-1} $$ control day: 78 . 8 ± 22 . 9 $$ 78.8\pm 22.9 $$ min - 1 $$ {}^{-1} $$ ). These results were consistent with those from the literature. CONCLUSION: We showed that the perfusion signal consists of two compartments of preglomerular flow and postglomerular flow. The proposed diffusion-weighted arterial spin labeling could measure the glomerular blood transfer rate ( k G $$ {k}_G $$ ), which was sensitive enough to noninvasively monitor the caffeine-induced vasodilation of afferent arterioles.