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Background: Lactate is a commonly used biomarker for sepsis, although it has limitations in certain cases, suggesting the need for novel biomarkers. We evaluated the diagnostic accuracy of plasma renin concentration and renin activity for mortality and kidney outcomes in patients with sepsis with hypoperfusion or hypotension., Methods: This was a multicenter, prospective, observational study of 117 patients with septic shock treated at three tertiary emergency departments between September 2021 and October 2022. The accuracy of renin activity, renin, and lactate concentrations in predicting 28-day mortality, acute kidney injury (AKI), and renal replacement requirement was assessed using the area under the ROC curve (AUC) analysis., Results: The AUCs of initial renin activity, renin, and lactate concentrations for predicting 28-day mortality were 0.66 (95% confidence interval [CI], 0.55-0.77), 0.63 (95% CI, 0.52-0.75), and 0.65 (95% CI, 0.53-0.77), respectively, and those at 24 hrs were 0.74 (95% CI, 0.62-0.86), 0.70 (95% CI, 0.56-0.83), and 0.67 (95% CI, 0.54-0.79). Renin concentrations and renin activity outperformed initial lactate concentrations in predicting AKI within 14 days. The AUCs of renin and lactate concentrations were 0.71 (95% CI, 0.61-0.80) and 0.57 (95% CI, 0.46-0.67), respectively ( P =0.030). The AUC of renin activity (0.70; 95% CI, 0.60-0.80) was also higher than that of lactate concentration ( P =0.044)., Conclusions: Renin concentration and renin activity show comparable performance to lactate concentration in predicting 28-day mortality in patients with septic shock but superior performance in predicting AKI.

Modern graphics processing units (GPUs) provide an unprecedented level of computing power. In this study, we present a high-performance, multi-GPU implementation of the analytical nuclear gradient for Kohn-Sham time-dependent density functional theory (TDDFT), employing the Tamm-Dancoff approximation (TDA) and Gaussian-type atomic orbitals as basis functions. We discuss GPU-efficient algorithms for the derivatives of electron repulsion integrals and exchange-correlation functionals within the range-separated scheme. As an illustrative example, we calculate the TDA-TDDFT gradient of the S 1 state of a full-scale green fluorescent protein with explicit water solvent molecules, totaling 4353 atoms, at the ωB97X/def2-SVP level of theory. Our algorithm demonstrates favorable parallel efficiencies on a high-speed distributed system equipped with 256 Nvidia A100 GPUs, achieving >70% with up to 64 GPUs and 31% with 256 GPUs, effectively leveraging the capabilities of modern high-performance computing systems.

Aim: We assessed the efficacy of anti-hyperkalemic agents for alleviating hyperkalemia and improving clinical outcomes in patients with out-of-hospital cardiac arrest (OHCA)., Methods: This was a single-center, retrospective observational study of OHCA patients treated at tertiary hospitals between 2010 and 2020. Adult patients aged 18 or older who were in cardiac arrest at the time of arrival and had records of potassium levels measured during cardiac arrest were included. A linear regression model was used to evaluate the relationship between changes in potassium levels and use of anti-hyperkalemic medications. Cox proportional hazards regression analysis was performed to analyze the relationship between the use of anti-hyperkalemic agents and the achievement of return of spontaneous circulation (ROSC)., Results: Among 839 episodes, 465 patients received anti-hyperkalemic medication before ROSC. The rate of ROSC was higher in the no anti-hyperkalemic group than in the anti-hyperkalemic group (55.9 % vs 47.7 %, P = 0.019). The decrease in potassium level in the anti-hyperkalemic group from pre-ROSC to post-ROSC was significantly greater than that in the no anti-hyperkalemic group (coefficient 0.38, 95 % confidence interval [CI], 0.13-0.64, P = 0.003). In Cox proportional hazards regression analysis, the use of anti-hyperkalemic medication was related to a decreased ROSC rate in the overall group (adjusted hazard ratio [aHR] 0.66, 95 % CI, 0.54-0.81, P < 0.001), but there were no differences among subgroups classified according to initial potassium levels., Conclusions: Anti-hyperkalemic agents were associated with substantial decreases in potassium levels in OHCA patients. However, administration of anti-hyperkalemic agents did not affect the achievement of ROSC., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Tae Gun Shin reports financial support was provided by 10.13039/501100003725National Research Foundation of Korea. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

The ever-increasing demand for rechargeable battery systems in the era of electric vehicles has spurred extensive research into developing polymeric components for batteries, such as separators, polymer electrolytes, and binders. However, current battery systems rely on expensive and nonrenewable resources, which potentially have a negative environmental impact. Therefore, polymer materials derived from natural resources have gained significant attention, primarily due to their cost-effective and environmentally sustainable features. Moreover, natural feedstocks often possess highly polar functional groups and high molecular weights, offering desirable electro-chemo-mechanical features when applied as battery materials. More recently, various recycling and upcycling strategies for polymeric battery components have also been proposed given the substantial waste generation from end-of-life batteries. Recycling polymeric materials includes an overall process of recovering the components from spent batteries followed by regeneration into new materials. Polymer upcycling into battery materials involves transforming daily-used plastic waste into high-value-added battery components. This review aims to give a state-of-the-art overview of contemporary methods to develop sustainable polymeric materials and recycling/upcycling strategies for various battery applications., (© 2024 Wiley-VCH GmbH.)

Objectives: To study the impact of a restrictive calcium replacement protocol in comparison with a liberal one in patients with septic shock., Material and Methods: Multicenter retrospective before-after study that estimated the impact of implementing a restrictive calcium replacement protocol in patients with septic shock. Patients admitted to an intensive care unit between May 2019 and April 2021 were assigned to liberal calcium replacement, and those admitted between May 2021 and April 2022 were assigned to a restrictive protocol. The primary outcome measure was 28-day mortality. Patients were matched with propensity scores., Results: A total of 644 patients were included; liberal replacement was used in 453 patients and the restrictive replacement in 191. We paired 553 patients according to propensity scores, 386 in the liberal group and 167 in the restrictive group. Mortality did not differ significantly between the groups at 28 days (35.3% vs 32.3%, respectively; hazard ratio, 0.97; 95% CI, 0.72-1.29) or after resolution of septic shock (81.5% vs 83.8%; hazard ratio, 0.89; 95% CI, 0.73-1.09). Nor did scores on the Sepsis-related Organ Failure Assessment scale differ (2.1 vs 2.6; P = 0.20)., Conclusion: The implementation of a restrictive calcium replacement protocol in patients with septic shock was not associated with a decrease in 28-day mortality in comparison with use of a liberal protocol. However, we were able to reduce calcium replacement without adverse effects.

Accurate postoperative assessment of varying mechanical properties is crucial for customizing patient-specific treatments and optimizing rehabilitation strategies following Achilles tendon (AT) rupture and reconstruction surgery. This study introduces a wireless, chip-less, and immune-tolerant in vivo strain-sensing suture designed to continuously monitor mechanical stiffness variations in the reconstructed AT throughout the healing process. This innovative sensing suture integrates a standard medical suturing thread with a wireless fiber strain-sensing system, which incorporates a fiber strain sensor and a double-layered inductive coil for wireless readout. The winding design of Au nanoparticle-based fiber electrodes and a hollow core contribute to the fiber strain sensor's high sensitivity (factor of 6.2 and 15.1 pF for revised sensitivity), negligible hysteresis, and durability over 10,000 stretching cycles. To ensure biocompatibility and immune tolerance during extended in vivo periods, an antibiofouling lubricant layer was applied to the sensing suture. Using this sensing system, we successfully monitored the strain responses of the reconstructed AT in an in vivo porcine model. This facilitated the postoperative assessment of mechanical stiffness variations through a well-established analytical model during the healing period.

Low skeletal muscle mass may develop in children with end-stage liver disease, affecting postoperative outcomes. We retrospectively investigated whether preoperative low muscle mass was associated with early postoperative outcomes in pediatric patients undergoing living donor liver transplantation (LDLT). Electronic medical records of children (age below 12 y) who underwent LDLT between February 1, 2007, and January 31, 2018, were reviewed. The cross-sectional areas of psoas, quadratus lumborum, and erector spinae muscles at the level of fourth-fifth lumbar intervertebral disks were measured using abdominal CT images, divided by the square of the height and were added to obtain the total skeletal muscle index (TSMI). The patients were divided into two groups according to the median TSMI in the second quintile (1859.1 mm 2 /m 2 ). Complications in the early postoperative period (within 30 d after surgery) classified as Clavien-Dindo grade 3 or higher were considered major complications. Logistic regression analyses were performed to determine the association between preoperative low muscle mass and early postoperative outcomes. In the study population of 123 patients (median age, 14 mo; range, 8-38 mo) who underwent LDLT, 29% and 71% were classified in the low (mean TSMI, 1642.5 ± 187.0 mm 2 /m 2 ) and high (mean TSMI 2188.1 ± 273.5 mm 2 /m 2 ) muscle mass groups, respectively. The rates of major complications, mechanical ventilation >96 hours, intensive care unit stay >14 days, hospital stay >30 days, and in-hospital mortality were not significantly different between the 2 groups. Additionally, adverse outcomes according to pediatric end-stage liver disease scores and sex were not significantly different between the 2 groups. In conclusion, preoperative low muscle mass defined by TSMI was not associated with early postoperative outcomes in pediatric patients undergoing LDLT., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Obesity has been increasing in many regions of the world, including Europe, USA, and Korea. To manage obesity, we should consider it as a disease and apply therapeutic methods for its treatment. Molecular and therapeutic approaches for obesity management involve regulating biomolecules such as DNA, RNA, and protein in adipose-derived stem cells to prevent to be fat cells. Multiple factors are believed to play a role in fat differentiation, with one of the most effective factor is Ca 2+ . We recently reported that the electromagnetic perceptive gene (EPG) regulated intracellular Ca 2+ levels under various electromagnetic fields. This study aimed to investigate whether EPG could serve as a therapeutic method against obesity. We confirmed that EPG serves as a modulator of Ca 2+ levels in primary adipose cells, thereby regulating several genes such as CasR, PPARγ, GLU4, GAPDH during the adipogenesis. In addition, this study also identified EPG-mediated regulation of myogenesis that myocyte transcription factors (CasR, MyoG, MyoD, Myomaker) were changed in C2C12 cells and satellite cells. In vivo experiments carried out in this study confirmed that total weight/ fat/fat accumulation were decreased and lean mass was increased by EPG with magnetic field depending on age of mice. The EPG could serve as a potent therapeutic agent against obesity., (© 2023. The Author(s).)

We sought to determine whether blade size influences the first-pass success (FPS) rate when performing endotracheal intubation (ETI) with a C-MAC video laryngoscope (VL) in emergency department (ED) patients. This single-center, retrospective, observational study was conducted between August 2016 and July 2022. A total of 1467 patients was divided into two categories based on the blade size used during the first ETI attempt: blade-3 (n = 365) and blade-4 groups (n = 1102). The primary outcome was the FPS rate. The secondary outcomes included the glottic view, multiple attempt rate, and ETI-related complications. We used propensity score matching to reduce the potential confounders between the two groups. Among these, 363 pairs of matched propensity scores were generated. The FPS rate did not differ between the blade-3 (84.8%) and blade-4 groups (87.3%) in the matched cohort ( p = 0.335). The multiple attempt rate did not differ significantly between groups ( p = 0.289) and was 3.9% and 2.5% in the blade-3 and blade-4 groups, respectively. The difficult glottic view (11.3 vs. 6.9%, p = 0.039) and complication rates (15.4% vs. 10.5%, p = 0.047) were significantly higher in the blade-3 group than in the blade-4 group. The FPS rates of ETI with the blade-3 and blade-4 groups in adult patients in the ED did not differ significantly.

Introduction: In this study we aimed to investigate the prognostic accuracy for predicting in-hospital mortality using respiratory Sequential Organ Failure Assessment (SOFA) scores by the conventional method of missing-value imputation with normal partial pressure of oxygen (PaO 2 )- and oxygen saturation (SpO 2 )-based estimation methods., Methods: This was a single-center, retrospective cohort study of patients with suspected infection in the emergency department. The primary outcome was in-hospital mortality. We compared the area under the receiver operating characteristics curve (AUROC) and calibration results of the conventional method (normal value imputation for missing PaO 2 ) and six SpO 2 -based methods: using methods A, B, PaO 2 is estimated by dividing SpO 2 by a scale; with methods C and D, PaO 2 was estimated by a mathematical model from a previous study; with methods E, F, respiratory SOFA scores was estimated by SpO 2 thresholds and respiratory support use; with methods A, C, E are SpO 2 -based estimation for all PaO 2 values, while methods B, D, F use such estimation only for missing PaO 2 values., Results: Among the 15,119 patients included in the study, the in-hospital mortality rate was 4.9%. The missing PaO 2 was 56.0%. The calibration plots were similar among all methods. Each method yielded AUROCs that ranged from 0.735-0.772. The AUROC for the conventional method was 0.755 (95% confidence interval [CI] 0.736-0.773). The AUROC for method C (0.772; 95% CI 0.754-0.790) was higher than that of the conventional method, which was an SpO 2 -based estimation for all PaO 2 values. The AUROC for total SOFA score from method E (0.815; 95% CI 0.800-0.831) was higher than that from the conventional method (0.806; 95% CI 0.790-0.822), in which respiratory SOFA was calculated by the predefined SpO 2 cut-offs and oxygen support., Conclusion: In non-ICU settings, respiratory SOFA scores estimated by SpO 2 might have acceptable prognostic accuracy for predicting in-hospital mortality. Our results suggest that SpO 2 -based respiratory SOFA score calculation might be an alternative for evaluating respiratory organ failure in the ED and clinical research settings., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. No author has professional or financial relationships with any companies that are relevant to this study. There are no conflicts of interest or sources of funding to declare.

A central challenge in practically using high-capacity silicon (Si) as anode materials for lithium-ion batteries is alleviating significant volume change of Si during cycling. One key to resolving the failure issues of Si is exploiting carefully designed polymer binders exhibiting mechanical robustness to retain the structural integrity of Si electrodes, while concurrently displaying elasticity and toughness to effectively dissipate external stresses exerted by the volume changes of Si. Herein, a highly elastic and tough polymer binder is proposed by interweaving polyacrylic acid (PAA) with poly(urea-urethane) (PUU) elastomer for Si anodes. By systematically tuning molecular parameters, including molecular weights of hard/soft segments and structures of hard segment components, it is demonstrated that the mechanical properties of polymer binders, such as elasticity, toughness, and stress relaxation ability, strongly affect the cycling performance of Si electrodes. This study provides new insight into the rational design of polymer binders capable of accommodating the volume changes of Si, primarily by judicious modulation of the mechanical properties of polymer binders., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

We investigated the prognostic performance of scoring systems by the intensive care unit (ICU) type. This was a retrospective observational study using data from the Marketplace for Medical Information in the Intensive Care IV database. The primary outcome was in-hospital mortality. We obtained Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation (APACHE) III, and Simplified Acute Physiology Score (SAPS) II scores in each ICU type. Prognostic performance was evaluated with the area under the receiver operating characteristic curve (AUROC) and was compared among ICU types. A total of 29,618 patients were analyzed, and the in-hospital mortality was 12.4%. The overall prognostic performance of APACHE III was significantly higher than those of SOFA and SAPS II (0.807, [95% confidence interval, 0.799-0.814], 0.785 [0.773-0.797], and 0.795 [0.787-0.811], respectively). The prognostic performance of SOFA, APACHE III, and SAPS II scores was significantly different between ICU types. The AUROC ranges of SOFA, APACHE III, and SAPS II were 0.723-0.826, 0.728-0.860, and 0.759-0.819, respectively. The neurosurgical and surgical ICUs had lower prognostic performance than other ICU types. The prognostic performance of scoring systems in patients with suspected infection is significantly different according to ICU type. APACHE III systems have the highest prediction performance. ICU type may be a significant factor in the prognostication.

Objectives: To identify the association between preoperative low muscle mass and early postoperative outcomes in pediatric patients undergoing total correction of tetralogy of Fallot (TOF)., Design: A retrospective cohort study., Setting: A single university hospital in Seoul, South Korea., Participants: Pediatric patients (≤3 years) who underwent total correction of TOF between May 2008 and February 2018., Interventions: None., Measurements and Main Results: Cross-sectional areas of the pectoralis and erector spinae muscles were measured using preoperative chest computed tomography (CT) scans, and adjusted to body surface area to define muscle mass index. The patients were divided into sarcopenia, presarcopenia, and no sarcopenia groups based on cutoff values determined using the mean and SD of the muscle mass index in the third z-weight quintile. Of a total of 330 patients included in the final analysis, 13 were associated with the sarcopenia group, 57 in the presarcopenia group, and 260 in the no sarcopenia group. The sarcopenia group exhibited a higher incidence of major adverse events than the presarcopenia and no sarcopenia groups, respectively (38% v 25% v 18%; p = 0.033). Logistic regression analyses revealed that only younger age at the time of surgery was significantly associated with major adverse events (odds ratio 0.82; 95% CI 0.72-0.94, p = 0.003)., Conclusions: The incidence of sarcopenia, as assessed by preoperative chest CT, was low in pediatric patients undergoing total correction of TOF, and preoperative sarcopenia did not predict early postoperative major adverse events., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: We compared the prognostic accuracy of in-hospital mortality of the initial Sequential Organ Failure Assessment (SOFA ini ) score at the time of sepsis recognition and resuscitation and the maximum SOFA score (SOFA max ) using the worst variables in the 24 h after the initial score measurement in emergency department (ED) patients with septic shock., Methods: This was a retrospective observational study using a multicenter prospective registry of septic shock patients in the ED between October 2015 and December 2019. The primary outcome was in-hospital mortality. The prognostic accuracies of SOFA ini and SOFA max were evaluated using the area under the receiver operating characteristic (AUC) curve., Results: A total of 4860 patients was included, and the in-hospital mortality was 22.1%. In 59.7% of patients, SOFA max increased compared with SOFA ini , and the mean change of total SOFA score was 2.0 (standard deviation, 2.3). There was a significant difference in in-hospital mortality according to total SOFA score and the SOFA component scores, except cardiovascular SOFA score. The AUC of SOFA max (0.71; 95% confidence interval [CI], 0.69-0.72) was significantly higher than that of SOFA ini (AUC, 0.67; 95% CI, 0.66-0.69) in predicting in-hospital mortality. The AUCs of all scores of the six components were higher for the maximum values., Conclusion: The prognostic accuracy of the initial SOFA score at the time of sepsis recognition was lower than the 24-h maximal SOFA score in ED patients with septic shock. Follow-up assessments of organ failure may improve discrimination of the SOFA score for predicting mortality., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background and Objectives : Cerebral ischemia is one of the major preoperative complications. Dexmedetomidine is a well-known sedative-hypnotic agent that has potential organ-protective effects. We examine the miRNAs associated with preconditioning effects of dexmedetomidine in cerebral ischemia. Materials and Methods : Transient infarcts were induced in mice via reperfusion after temporary occlusion of one side of the middle cerebral artery. A subset of these mice was exposed to dexmedetomidine prior to cerebral infarction and miRNA profiling of the whole brain was performed. We administered dexmedetomidine and miRNA-323-5p mimic/inhibitor to oxygen-glucose deprivation/reoxygenation astrocytes. Additionally, we administered miR-323-5p mimic and inhibitor to mice via intracerebroventricular injection 2 h prior to induction of middle cerebral artery occlusion. Results : The infarct volume was significantly lower in the dexmedetomidine-preconditioned mice. Analysis of brain samples revealed an increased expression of five miRNAs and decreased expression of three miRNAs in the dexmedetomidine-pretreated group. The viability of cells significantly increased and expression of miR-323-5p was attenuated in the dexmedetomidine-treated oxygen-glucose deprivation/reoxygenation groups. Transfection with anti-miR-323-5p contributed to increased astrocyte viability. When miRNA-323-5p was injected intraventricularly, infarct volume was significantly reduced when preconditioned with the miR-323-5p inhibitor compared with mimic and negative control. Conclusions : Dexmedetomidine has a protective effect against transient neuronal ischemia-reperfusion injury and eight specific miRNAs were profiled. Also, miRNA-323-5p downregulation has a cell protective effect under ischemic conditions both in vivo and in vitro. Our findings suggest the potential of the miR-323-5p inhibitor as a therapeutic agent against cerebral infarction.

Extracorporeal shockwave therapy (ESWT) can induce wound healing by increasing tissue microcirculation. However, studies on the effect of ESWT on enhancing tissue microcirculation in diabetic foot ulcer (DFU), particularly on when the microcirculation increases after ESWT application, are still lacking. Therefore, we aimed to examine the effectiveness of ESWT in promoting microcirculation in DFU patients in a time-dependent manner. We included 50 feet of 25 patients with type 2 diabetes mellitus and Wagner grade I to II DFU in this study. The affected feet were used as the ESWT group and the unaffected contralateral feet were used as the control group. ESWT was performed in 3 sessions per week for a total of 3 weeks. Transcutaneous partial oxygen pressure (TcPO2) was used to evaluate the tissue microcirculation. The TcPO2 level (>43 mm Hg) in the ESWT group was recovered by the 2nd week of treatment, and statistical significance (P < .05) was demonstrated at the same time. From the 2nd week of ESWT, a significant increase in TcPO2 was observed in Wagner grade I and II DFU. These findings imply that the ESWT may improve microcirculation in patients with Wagner grades I to II DFU. However, this impact requires at least 2 weeks or more than 6 sessions. For better comparison, further studies with larger clinical groups and extended period are needed., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The adolescent social experience is essential for the maturation of the prefrontal cortex in mammalian species. However, it still needs to be determined which cortical circuits mature with such experience and how it shapes adult social behaviors in a sex-specific manner. Here, we examined social-approaching behaviors in male and female mice after postweaning social isolation (PWSI), which deprives social experience during adolescence. We found that the PWSI, particularly isolation during late adolescence, caused an abnormal increase in social approaches (hypersociability) only in female mice. We further found that the PWSI female mice showed reduced parvalbumin (PV) expression in the left orbitofrontal cortex (OFC L ). When we measured neural activity in the female OFC L , a substantial number of neurons showed higher activity when mice sniffed other mice (social sniffing) than when they sniffed an object (object sniffing). Interestingly, the PWSI significantly reduced both the number of activated neurons and the activity level during social sniffing in female mice. Similarly, the CRISPR/Cas9-mediated knockdown of PV in the OFC L during late adolescence enhanced sociability and reduced the social sniffing-induced activity in adult female mice via decreased excitability of PV + neurons and reduced synaptic inhibition in the OFC L Moreover, optogenetic activation of excitatory neurons or optogenetic inhibition of PV + neurons in the OFC L enhanced sociability in female mice. Our data demonstrate that the adolescent social experience is critical for the maturation of PV + inhibitory circuits in the OFC L ; this maturation shapes female social behavior via enhancing social representation in the OFC L SIGNIFICANCE STATEMENT Adolescent social isolation often changes adult social behaviors in mammals. Yet, we do not fully understand the sex-specific effects of social isolation and the brain areas and circuits that mediate such changes. Here, we found that adolescent social isolation causes three abnormal phenotypes in female but not male mice: hypersociability, decreased PV + neurons in the left orbitofrontal cortex (OFC L ), and decreased socially evoked activity in the OFC L Moreover, parvalbumin (PV) deletion in the OFC L in vivo caused the same phenotypes in female mice by increasing excitation compared with inhibition within the OFC L Our data suggest that adolescent social experience is required for PV maturation in the OFC L , which is critical for evoking OFC L activity that shapes social behaviors in female mice., Competing Interests: The authors declare no competing financial interests., (Copyright © 2023 the authors.)

An aberrant late sodium current (I Na,Late ) caused by a mutation in the cardiac sodium channel (Na v 1.5) has emerged as a contributor to electrical remodeling that causes susceptibility to atrial fibrillation (AF). Although downregulation of phosphoinositide 3-kinase (PI3K)/Akt signaling is associated with AF, the molecular mechanisms underlying the negative regulation of I Na,Late in AF remain unclear, and potential therapeutic approaches are needed. In this work, we constructed a tachypacing-induced cellular model of AF by exposing HL-1 myocytes to rapid electrical stimulation (1.5 V/cm, 4 ms, 10 Hz) for 6 h. Then, we gathered data using confocal Ca 2+ imaging, immunofluorescence, patch-clamp recordings, and immunoblots. The tachypacing cells displayed irregular Ca 2+ release, delayed afterdepolarization, prolonged action potential duration, and reduced PI3K/Akt signaling compared with controls. Those detrimental effects were related to increased I Na,Late and were significantly mediated by treatment with the I Na,Late blocker ranolazine. Furthermore, decreased PI3K/Akt signaling via PI3K inhibition increased I Na,Late and subsequent aberrant myocyte excitability, which were abolished by I Na,Late inhibition, suggesting that PI3K/Akt signaling is responsible for regulating pathogenic I Na,Late . These results indicate that PI3K/Akt signaling is critical for regulating I Na,Late and electrical remodeling, supporting the use of PI3K/Akt-mediated I Na,Late as a therapeutic target for AF., (© 2022. The Author(s).)

This study aimed to determine the impact of modifications in emergency department (ED) practices caused by the coronavirus disease 2019 (COVID-19) pandemic on the clinical outcomes and management of patients with septic shock. We performed a retrospective study. Patients with septic shock who presented to the ED between 1 January 2018 and 19 January 2020 were allocated to the pre-COVID-19 group, whereas those who presented between 20 January 2020 and 31 December 2020 were assigned to the post-COVID-19 group. We used propensity score matching to compare the sepsis-related interventions and clinical outcomes. The primary outcome measure was in-hospital mortality. Of the 3697 patients included, 2254 were classified as pre-COVID-19 and 1143 as post-COVID-19. A total of 1140 propensity score-matched pairings were created. Overall, the in-hospital mortality rate was 25.5%, with no statistical difference between the pre- and post-COVID-19 groups (p = 0.92). In a matched cohort, the post-COVID-19 group had delayed lactate measurement, blood culture test, and infection source control (all p < 0.05). There was no significant difference in time to antibiotics (p = 0.19) or vasopressor administration (p = 0.09) between the groups. Although sepsis-related interventions were delayed during the COVID-19 pandemic, there was no significant difference in the in-hospital mortality between the pre- and post-COVID-19 groups.

Sodium metal batteries have been emerging as promising candidates for post-Li battery systems owing to the natural abundance, low costs, and high energy density of Na metal. However, exploiting an Na metal anode is accompanied by uncontrolled Na electrodeposition, particularly concerning dendrite growth, hampering practical Na metal battery applications. Herein, we propose sodiophilic gel polymer electrolytes with a porosity-gradient Janus structure to alleviate Na dendrite growth. Tethering only 1.1 mol % sodiophilic poly(ethylene glycol) to poly(vinylidene fluoride- co -hexafluoropropylene) suppresses Na dendrites by regulating homogeneous Na + distribution, which relies on molecular-level coordination between Na + and the sodiophilic functional groups. By exploiting the porosity-gradient Janus structure, we have demonstrated that regular porosity and well-defined morphology of polymer electrolytes, particularly at the Na/electrolyte interface, significantly impact dendrite growth. This study provides new insights into the rational design of Na dendrite-suppressing polymer electrolytes, primarily focusing on the ion-regulating ability achieved by surface engineering.

This study sought to determine whether the C-MAC video laryngoscope (VL) performed better than a direct laryngoscope (DL) when attempting endotracheal intubation (ETI) in the emergency department (ED) while wearing personal protective equipment (PPE). This was a retrospective single-center observational study conducted in an academic ED between February 2020 and March 2022. All emergency medical personnel who participated in any ETI procedure were required to wear PPE. The patients were divided into the C-MAC VL group and the DL group based on the device used during the first ETI attempt. The primary outcome measure was the first-pass success (FPS) rate. A multiple logistic regression was used to determine the factors associated with FPS. Of the 756 eligible patients, 650 were assigned to the C-MAC group and 106 to the DL group. The overall FPS rate was 83.5% (n = 631/756). The C-MAC group had a significantly higher FPS rate than the DL group (85.7% vs. 69.8%, p < 0.001). In the multivariable logistic regression analysis, C-MAC use was significantly associated with an increased FPS rate (adjusted odds ratio, 2.86; 95% confidence interval, 1.69−4.08; p < 0.001). In this study, we found that the FPS rate of ETI was significantly higher when the C-MAC VL was used than when a DL was used by emergency physicians constrained by cumbersome PPE.

Functional recovery following traumatic brain injury (TBI) is limited due to progressive neuronal damage resulting from secondary injury-associated neuroinflammation. Steroidal anti-inflammatory drugs, such as dexamethasone (DX), can reduce neuroinflammation by activated microglia and infiltrated macrophages. In our previous work, we developed hydrolytically degradable poly(ethylene) glycol-bis-(acryloyloxy acetate) (PEG-bis-AA) hydrogels with dexamethasone (DX)-conjugated hyaluronic acid (HA-DXM) and demonstrated that dexamethasone-loaded hydrogels (PEG-bis-AA/HA-DXM) can reduce neuroinflammation, apoptosis, and lesion volume and improve neuronal cell survival and motor function recovery at seven days post-injury (DPI) in a rat mild-TBI model. In this study, we investigate the effects of the local application of PEG-bis-AA/HA-DXM hydrogels on motor function recovery at 7 DPI and cognitive functional recovery as well as secondary injury at 14 DPI in a rat mild-CCI TBI model. We observed that PEG-bis-AA/HA-DXM-treated animals exhibit significantly improved motor functions by the rotarod test and cognitive functions by the Morris water maze test compared to untreated TBI animals. We also observed that PEG-bis-AA/HA-DXM hydrogels reduce the inflammatory response, apoptosis, and lesion volume compared to untreated animals at 14 DPI. Therefore, PEG-bis-AA/HA-DXM hydrogels can be promising a therapeutic intervention for TBI treatment.

To determine the minimum number of endotracheal intubation (ETI) attempts necessary for a novice emergency medicine (EM) trainee to become proficient with this procedure. This single-center study retrospectively analyzed data obtained from the institutional airway registry during the period from April 2014 to March 2021. All ETI attempts made by EM trainees starting their residency programs between 2014 and 2018 were evaluated. We used a first attempt success (FAS) rate of 85% as a proxy for ETI proficiency. Generalized linear mixed models were used to evaluate the association between FAS and cumulative ETI experience. The number of ETI attempts required to achieve an FAS rate of ≥ 85% was estimated using the regression coefficients obtained from the model. The study period yielded 2077 ETI cases from a total of 1979 patients. The FAS rate was 78.6% (n = 1632/2077). After adjusting for confounding factors, the cumulative number of ETI cases was associated with increased FAS (adjusted odds ratio, 1.010 per additional ETI case; 95% confidence interval 1.006-1.013; p &lt; 0.001). A minimum of 119 ETI cases were required to establish a ≥ 85% likelihood of FAS. At least 119 ETI cases were required for EM trainees to achieve an FAS rate of ≥ 85% in the emergency department., (© 2022. The Author(s).)

Objective: We evaluated the performance of diastolic shock index (DSI) and lactate in predicting vasopressor requirement among hypotensive patients with suspected infection in an emergency department., Methods: This was a single-center, retrospective observational study for adult patients with suspected infection and hypotension in the emergency department from 2018 to 2019. The study population was split into derivation and validation cohorts (70/30). We derived a simple risk score to predict vasopressor requirement using DSI and lactate cutoff values determined by Youden index. We tested the score by the area under the receiver operating characteristic curve (AUC). We performed a multivariable regression analysis to evaluate the association between the timing of vasopressor treatment and 28-day mortality., Results: A total of 1,917 patients were included. We developed a score, assigning 1 point each for the high DSI (≥2.0) and high lactate (≥2.5 mmol/L) criteria. The AUCs of the score were 0.741 (95% confidence interval [CI], 0.715-0.768) at hypotension and 0.736 (95% CI, 0.708-0.763) after initial fluid challenge in the derivation cohort and 0.676 (95% CI, 0.631-0.719) at hypotension and 0.688 (95% CI, 0.642-0.733) after initial fluid challenge in the validation cohort, respectively. In patients with scores of 2 points, early vasopressor therapy initiation was significantly associated with decreased 28-day mortality (adjusted odds ratio, 0.37; 95% CI, 0.14-0.94)., Conclusion: A prediction model with DSI and lactate levels might be useful to identify patients who are more likely to need vasopressor administration among hypotensive patients with suspected infection.

The prognostic value of low vitamin C levels has not been well investigated in patients with septic shock. We aimed to evaluate the association of vitamin C deficiency with mortality in patients with septic shock. We conducted a retrospective analysis of 165 patients with septic shock from a prospective multicenter trial and institutional sepsis registry between April 2018 and January 2020. The primary outcome was 28-day mortality. The patients were categorized into vitamin C deficiency and normal groups based on a vitamin C cutoff level of 11.4 mmol/L. Multivariable Cox regression analysis was performed to examine the association between vitamin C levels and 28-day mortality. A total of 165 patients was included for analysis and 77 (46.7%) had vitamin C deficiency. There was no significant difference in the 28-day mortality rate between the vitamin C deficiency group and the normal group (23.4% ( n = 18/77) vs. 13.6% ( n = 12/88), p = 0.083). Multivariable Cox proportional hazard analysis showed vitamin C deficiency to be associated with increased risk of 28-day mortality (adjusted hazard ratio, 2.65, 95% confidence interval (CI), 1.08-6.45; p = 0.032). Initial vitamin C deficiency was associated with a higher risk of 28-day mortality in patients with septic shock after adjusting for intravenous administration of vitamin C and thiamine, baseline characteristics, laboratory findings, and severity of illness., Competing Interests: The authors declare no conflict of interest.

An effective wound management strategy needs accurate assessment of wound status throughout the whole healing process. This can be achieved by examining molecular biomarkers including proteins, DNAs, and RNAs. However, existing methods for quantifying these biomarkers such as immunohistochemistry and quantitative polymerase chain reaction are usually laborious, resource-intensive, and disruptive. This article reports the development and utilization of mRNA nanosensors (i.e., NanoFlare) that are topically applied on cutaneous wounds to reveal the healing status through targeted and semi-quantitative examination of the mRNA biomarkers in skin cells. In 2D and 3D in vitro models, the efficacy and efficiency of these nanosensors are demonstrated in revealing the dynamic changes of mRNA biomarkers for different stages of wound development. In mouse models, this platform permits the tracking and identification of wound healing stages and a normal and diabetic wound healing process by wound healing index in real time., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Aim: This study investigated whether prehospital advanced airway management (AAM) is associated with improved survival of out-of-hospital cardiac arrest (OHCA) compared with conventional bag-valve-mask (BVM) ventilation., Methods: We investigated the neurologically favorable survival of adult patients with OHCA who underwent BVM or AAM using the Korean Cardiac Arrest Research Consortium (KoCARC), a multicenter OHCA registry of Korea. The differences in clinical characteristics were adjusted by matching or weighting the clinical propensity for use of AAM or by least absolute shrinkage and selection operator (LASSO). The primary outcome was 30-day survival with neurologically favorable status defined by cerebral performance category 1 or 2., Results: Of the 9,616 patients enrolled (median age = 71 years; 65% male), there were 6,243 AAM and 3,354 BVM patients. In unadjusted analysis, the 30-day neurologically favorable survival was lower in the AAM group compared with the BVM group (5.5% vs. 10.0%; hazard ratio [HR] = 1.21, 95% confidence interval [CI] = 1.16 to 1.27; all p < 0.001). In propensity score matching-adjusted analysis, these differences were not found (9.6% vs. 10.0%; HR = 0.98, 95% CI = 0.93 to 1.03, p > 0.05). Inverse probability of treatment weighting- and LASSO-adjusted analyses replicated these results., Conclusions: In this nationwide real-world data analysis of OHCA, the 30-day neurologically favorable survival did not differ between prehospital AAM and BVM after adjustment for clinical characteristics., (© 2022 Society for Academic Emergency Medicine.)

Background: Despite potential clinical roles of extracorporeal life support (ECLS) for out-of-hospital cardiac arrest (OHCA) compared to that of conventional cardiopulmonary resuscitation (CCPR), use of ECLS for OHCA is not strongly endorsed by current clinical guidelines., Objective: The purpose of this study is to investigate the clinical roles of extracorporeal life support (ECLS) compared with that of conventional cardiopulmonary resuscitation (CCPR) for out-of-hospital cardiac arrest (OHCA) patients., Methods: The outcomes of OHCA between 2015 and 2020, enrolled in the Korean Cardiac Arrest Research Consortium (KoCARC), a multicenter OHCA patient registry including 65 participating hospitals throughout the Republic of Korea (ClinicalTrials.gov, number NCT03222999). Differences in clinical features were adjusted by matching the propensity for ECLS. The primary outcome was 30-day neurologically favorable survival with cerebral performance category of 1 or 2. Restricted mean survival time (RMST) was used to compare outcomes between groups., Results: Of 12,006 patients included, ECLS was applied to 272 patients (2.2%). The frequency of neurologically favorable survival was higher in the ECLS group than the CCPR group (RMST difference, 5.5 days [95% CI, 4.1-7.0 days], P < 0.001). In propensity score-matched 271 pairs, the clinical outcome of ECLS and CCPR did not differ to a statistically significant extent (RMST difference, 0.4 days [95% CI -1.6 to 2.5 days], P = 0.67). Subgroup analyses revealed that the clinical roles of ECLS was evident in patients with nonshockable rhythm or CPR time ≥20 min (RMST difference, 2.7 days [95% CI 0.5-4.8 days], P = 0.015), but not in patients without these features (RMST difference, -3.7 days [95% CI -7.6 to 0.2 days], P = 0.07)., Conclusions: In this real-world data analysis, ECLS compared to CCPR did not result in better overall clinical outcomes of OHCA. The clinical efficacy of ECLS may be limited to a subgroup of high-risk patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by the Shock Society.)

Aim: To develop poly(lactide- co -glycolide)-graft-polyethylenimine (PgP) as a nanocarrier for the delivery of rolipram (Rm) and evaluate the therapeutic efficacy of Rm-loaded PgP (Rm-PgP) on secondary injury and motor function in a rat traumatic brain injury (TBI) model. Materials & methods: Rm-PgP was injected in the injured brain lesion immediately after TBI using a microinjection pump. Secondary injury pathologies such as inflammatory response, apoptosis and astrogliosis were assessed by histological analysis and functional recovery was assessed by assorted motor function tests. Results: Rm-PgP restored cyclic adenosine monophosphate level in the injured brain close to the sham level and Rm-PgP treatment reduced lesion volume, neuroinflammation and apoptosis and improved motor function at 7 days post-TBI. Conclusion: One single injection of Rm-PgP can be effective for acute mild TBI treatment.

To utilize thermally activated delayed fluorescence (TADF) technology for future displays, it is necessary to develop host materials which harness the full potential of blue TADF emitters. However, no publication has reported such hosts yet. Although the most popular host for blue TADF, bis[2-(diphenylphosphino)phenyl]ether oxide (DPEPO) guarantees high-maximum external quantum efficiency (EQE max ) TADF devices, they exhibit very short operational lifetimes. In contrast, long-lifespan blue TADF devices employing stable hosts such as 3',5-di(9H-carbazol-9-yl)-[1,1'-biphenyl]-3-carbonitrile (mCBP-CN) exhibit much lower EQE max than the DPEPO-employed devices. Here, an elaborative approach for designing host molecules is suggested to achieve simultaneously stable and efficient blue TADF devices. The approach is based on engineering the molecular geometry, ground- and excited-state dipole moments of host molecules. The engineered hosts significantly enhance delayed fluorescence quantum yields of TADF emitters, as stabilizing the charge-transfer excited states of the TADF emitters and suppressing exciton quenching, and improve the charge balance. Moreover, they exhibit both photochemical and electrochemical stabilities. The best device employing one of the engineered hosts exhibits 79% increase in EQE max compared to the mCBP-CN-employed device, together with 140% and 92-fold increases in operational lifetime compared to the respective mCBP-CN- and the DPEPO-based devices., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: Ventricular-arterial coupling is the ratio of arterial elastance to ventricular end-systolic elastance., Aims: The objective of this study was to determine the clinical implication of intraoperative ventricular-arterial coupling derived from the pressure-area relationship using transesophageal echocardiography., Methods: This retrospective study reviewed the medical records of 72 pediatric patients with ventricular septal defects who underwent corrective surgery with cardiopulmonary bypass. The single-beat modified method was used to assess ventricular-arterial coupling. Logistic regression analyses were performed to determine the correlation between ventricular-arterial coupling and early postoperative outcomes, including the maximum vasoactive-inotropic score, length of mechanical ventilation, and length of hospital stay., Results: Ventricular-arterial coupling after cardiopulmonary bypass significantly increased (from 1.0 ± 0.4 to 1.4 ± 0.8, p < .001), indicating a disproportionate increase in the arterial elastance index (from 11.5 ± 5.1 to 19.8 ± 7.5 mmHg/cm 2 /m 2 , p < .001) compared with the ventricular end-systolic elastance index (from 13.0 ± 6.9 to 16.9 ± 9.0 mmHg/cm 2 /m 2 , p < .001). Logistic regression analyses revealed that high postoperative ventricular-arterial coupling was independently associated with higher postoperative maximum vasoactive-inotropic score (>10; odds ratio [OR], 8.04; 95% confidence interval [CI], 1.38-46.85, p = .020), longer postoperative mechanical ventilation (>15 h; OR: 11.00; 95% CI: 1.26-96.45, p = .030), and longer postoperative hospital stay (>7 days; OR: 2.98; 95% CI: 1.04-8.58, p = .043)., Conclusions: Ventricular-arterial coupling can be easily obtained from the intraoperative transesophageal echocardiography in pediatric patients undergoing ventricular septal defects repair. High postoperative ventricular-arterial coupling is strongly associated with worse early postoperative outcomes. Ventricular-arterial coupling shows promise as an intraoperative analysis tool that can provide insight into the impact of interventions on cardiovascular performance and identify potential targets for treatment in this population., (© 2021 John Wiley & Sons Ltd.)

Although the organic light-emitting diode (OLED) has been successfully commercialized, the development of deep-blue OLEDs with high efficiency and long lifetime remains a challenge. Here, a novel hyperfluorescent OLED that incorporates the Pt(II) complex (PtON7-dtb) as a phosphorescent sensitizer and a hydrocarbon-based and multiple resonance-based fluorophore as an emitter (TBPDP and ν-DABNA) in the device emissive layer (EML), is proposed. Such an EML system can promote efficient energy transfer from the triplet excited states of the sensitizer to the singlet excited states of the fluorophore, thus significantly improving the efficiency and lifetime of the device. As a result, a deep-blue hyperfluorescent OLED using a multiple resonance-based fluorophore (ν-DABNA) with Commission Internationale de L'Eclairage chromaticity coordinate y below 0.1 is demonstrated, which attains a narrow full width at half maximum of ≈17 nm, fourfold increased maximum current efficiency of 48.9 cd A -1 , and 19-fold improved half-lifetime of 253.8 h at 1000 cd m -2 compared to a conventional phosphorescent OLED. The findings can lead to better understanding of the hyperfluorescent OLEDs with high performance., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

A cathode-coating material composed of cationic polymer-grafted graphene oxide (CPGO) and carbon nanotube (CNT) was prepared, where the CPGO was synthesized by grafting quaternized 2-(dimethylamino)ethyl methacrylate (QDMAEMA) onto graphene oxide (GO) via atom transfer radical polymerization (ATRP). GO has good compatibility with carbon black, the main component of the cathode in lithium-sulfur (Li-S) batteries. Here, the cationic polymer having the QDMAEMA unit was intentionally grafted onto GO to decrease the shuttle effect by increasing the chemical adsorption of polysulfide (PS). In addition, when CNT was mixed with CPGO, the compatibility with carbon black was found to be further increased. The lithium-sulfur (Li-S) battery with a sulfur-deposited Super P® carbon black (S/C) cathode coated with a mixture of CPGO and CNT was found to have much improved cell performance compared to those coated without any coating material, with only CPGO, with the mixture of GO and CNT, and with the mixture of PQDMAEMA and CNT. For example, the Li-S battery with the cathode coated using the mixture of CPGO and CNT retained a discharge capacity of 744 mA h g -1 after 50 cycles at 0.2C-rate, while those of the Li-S batteries with bare S/C and CPGO-S/C cathodes were found to be much smaller, i.e. , 488 mA h g -1 and 641 mA h g -1 , respectively, under the same conditions. Therefore, the mixture of CPGO with CNT as the cathode-coating material showed a synergetic effect to enhance the cell performance of the Li-S battery system., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We present trace gas vertical profiles observed by instruments on the NASA DC-8 and at a ground site during the Korea-US air quality study (KORUS) field campaign in May to June 2016. We focus on the region near the Seoul metropolitan area and its surroundings where both anthropogenic and natural emission sources play an important role in local photochemistry. Integrating ground and airborne observations is the major research goal of many atmospheric chemistry field campaigns. Although airborne platforms typically aim to sample from near surface to the free troposphere, it is difficult to fly very close to the surface especially in environments with complex terrain or a populated area. A detailed analysis integrating ground and airborne observations associated with specific concentration footprints indicates that reactive trace gases are quickly oxidized below an altitude of 700 m. The total OH reactivity profile has a rapid decay in the lower part of troposphere from surface to the lowest altitude (700 m) sampled by the NASA DC-8. The decay rate is close to that of very reactive biogenic volatile organic compounds such as monoterpenes. Therefore, we argue that photochemical processes in the bottom of the boundary layer, below the typical altitude of aircraft sampling, should be thoroughly investigated to properly assess ozone and secondary aerosol formation.

The INO80 chromatin remodeling complex has roles in many essential cellular processes, including DNA replication. However, the mechanisms that regulate INO80 in these processes remain largely unknown. We previously reported that the stability of Ino80, the catalytic ATPase subunit of INO80, is regulated by the ubiquitin proteasome system and that BRCA1-associated protein-1 (BAP1), a nuclear deubiquitinase with tumor suppressor activity, stabilizes Ino80 via deubiquitination and promotes replication fork progression. However, the E3 ubiquitin ligase that targets Ino80 for proteasomal degradation was unknown. Here, we identified the C-terminus of Hsp70-interacting protein (CHIP), the E3 ubiquitin ligase that functions in cooperation with Hsp70, as an Ino80-interacting protein. CHIP polyubiquitinates Ino80 in a manner dependent on Hsp70. Contrary to our expectation that CHIP degrades Ino80, CHIP instead stabilizes Ino80 by extending its halflife. The data suggest that CHIP stabilizes Ino80 by inhibiting degradative ubiquitination. We also show that CHIP works together with BAP1 to enhance the stabilization of Ino80, leading to its chromatin binding. Interestingly, both depletion and overexpression of CHIP compromise replication fork progression with little effect on fork stalling, as similarly observed for BAP1 and Ino80, indicating that an optimal cellular level of Ino80 is important for replication fork speed but not for replication stress suppression. This work therefore idenitifes CHIP as an E3 ubiquitin ligase that stabilizes Ino80 via nondegradative ubiquitination and suggests that CHIP and BAP1 act in concert to regulate Ino80 ubiquitination to fine-tune its stability for efficient DNA replication.

Traumatic brain injury (TBI) is a leading cause of death and disability with complex pathophysiology including prolonged neuroinflammation, apoptosis, and glial scar formation. The upregulation of RhoA is a key factor in the pathological development of secondary injury following TBI. Previously, we developed a novel cationic, amphiphilic copolymer, poly (lactide-co-glycolide)-graft-polyethylenimine (PgP), as a nanocarrier for delivery of therapeutic nucleic acids. In a rat compression spinal cord injury model, delivery of siRNA targeting RhoA (siRhoA) by PgP resulted in RhoA knockdown; reduced astrogliosis and inflammation; and promoted axonal regeneration/sparing. Here, we evaluated the effect of RhoA knockdown by PgP/siRhoA nanoplexes in a rat controlled cortical impact TBI model. A single intraparenchymal injection of PgP/siRhoA nanoplexes significantly reduced RhoA expression, lesion volume, neuroinflammation, and apoptosis, and increased neuronal survival in the ipsilateral cortex. These results suggest that PgP/siRhoA nanoplexes can efficiently knockdown RhoA expression in the injured brain and reduce secondary injury., (Copyright © 2020. Published by Elsevier Inc.)

Recent breakthroughs in neuroanatomical tracing methods have helped unravel complicated neural connectivity in whole-brain tissue at single-cell resolution. However, in most cases, analysis of brain images remains dependent on highly subjective and sample-specific manual processing, preventing precise comparison across sample animals. In the present study, we introduce AMaSiNe, software for automated mapping of single neurons in the standard mouse brain atlas with annotated regions. AMaSiNe automatically calibrates misaligned and deformed slice samples to locate labeled neuronal positions from multiple brain samples into the standardized 3D Allen Mouse Brain Reference Atlas. We exploit the high fidelity and reliability of AMaSiNe to investigate the topographic structures of feedforward projections from the lateral geniculate nucleus to the primary visual area by reconstructing rabies-virus-injected brain slices in 3D space. Our results demonstrate that distinct organization of neural projections can be precisely mapped using AMaSiNe., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

This study concerns the development of a well-defined synthetic route to obtain lignin-derived multifunctional graft polymers by simple chemical modification and atom-transfer radical polymerization. By grafting ion-conducting and cross-linkable moieties onto the lignin, star-shaped functional polymers are prepared. Upon cross-linking under ultraviolet light irradiation, the resulting polymer network exhibits mechanical stability even at high temperature, whereas the chain mobility is maintained despite the cross-linked structure. Their use as solid polymer electrolytes (SPEs) and binders for all-solid-state lithium metal batteries (LMBs) is also evaluated. The lignin-derived graft polymers provide a facile ion conduction pathway and also efficiently suppress lithium dendrite growth during cycling, thereby attaining excellent cycling performance for the LMB cell compared to that with a conventional liquid electrolyte-Celgard system., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Central visual field (CVF) loss is important in maintaining vision-related quality of life in eyes with open-angle glaucoma (OAG). The present study investigated whether nasalized location of central retinal vessel trunk (CRVT) at baseline is associated with rapid rate of CVF loss in early-stage OAG eyes. This study included 76 OAG eyes with high nasalization CRVT [HNL] group and 75 OAG eyes with low nasalization CRVT [LNL] group matched for glaucoma severity at baseline that showed progressive visual field (VF) loss. The rates of mean threshold changes at various regions were compared in the two groups using a linear mixed model. Clinical variables associated with rapid rate of CVF progression were also identified using a linear mixed model. The rate of CVF loss in the central 10° was significantly higher in the HNL group than that in the LNL group (-0.452 dB/year vs. -0.291 dB/year, P < 0.001). The average and inferior hemi-macular ganglion cell inner plexiform layer (GCIPL) progression rates were significantly faster in the HNL group than in the LNL group (P < 0.05). Nasalized location of CRVT was an independent predictor of a more rapid VF loss in the central 10° region (P < 0.05).

The dark dissolution behavior of plattnerite (ß-PbO 2 ) was investigated in frozen solutions containing halide ions and compared with those in aqueous solution. The amount of dissolved lead in the frozen solutions varied depending on the solution pH and the kind and concentration of halide ions. The presence of bromide and iodide ions enhanced the dissolution of lead in the aqueous phase, whereas the effect of chloride was insignificant. Compared with the aqueous phase dissolution, ß-PbO 2 dissolution in the frozen solution was slightly enhanced in the presence of bromide but suppressed in the presence of iodide. Iodide ions seemed to be relatively more trapped in the bulk ice (ice-crystal lattice) than bromide ions, which might be related to the suppressed dissolution of lead oxide in the presence of iodide. The co-existence of bromide (or iodide) and chloride ions in the frozen solution enhanced the dissolution of lead, which seems to be enabled by an additional reaction pathway involving the formation of mixed halide radicals, whereas such kind of synergistic enhancements were not observed in aqueous solution. The halide-induced lead oxide dissolution in frozen solutions can be related to the behavior of lead ions found in various media of frozen environments., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: To investigate the hypothesis that macular structure, function, and vessel density (VD) measurements can predict foveal threshold (FT) outcomes in glaucomatous eyes., Materials and Methods: One hundred ninety-five eyes from 195 subjects (134 subjects with early-to-moderate stage open-angle glaucoma and 61 healthy controls) who underwent optical coherence tomography angiography imaging and 24-2 visual field (VF) testing with FT measurements on the same day were retrospectively enrolled in this study. The association of FT with macular structural/functional/VD measurements was evaluated using partial correlation analyses with adjustment for age and linear regression analyses., Results: FT showed significant correlations between the thickness of the macular ganglion cell-inner plexiform layer (mGCIPL) (r=0.330, P<0.001) and the mean sensitivity (MS) of the central 5 and 10 degrees VF points (r=0.448, P<0.001 and r=0.361, P<0.001). Significant correlations were also found between FT and VD measurements at the inferior and superior parafoveal sectors (r=0.455, P<0.001 and r=0.438, P<0.001). In multivariate linear regression analyses controlling the covariates, the thickness of the mGCIPL, central 5 degrees VF MS, and parafoveal VD were significantly associated with FT (all P<0.001). There was also a significant association between FT and logMAR best-corrected visual acuity (β=-5.647, P<0.001)., Conclusions: Macular VD along with mGCIPL thickness and central 5 degrees VF MS independently predict FT outcomes even in the eyes of patients with early-to-moderate stage open-angle glaucoma.

Purpose: To investigate the effect of refractive error on the physiologic thinning rate of the retinal nerve fiber layer (RNFL) in healthy eyes. Materials and Methods . This study analyzed 223 eyes of 141 healthy subjects followed for more than 5 years and underwent at least five serial spectral domain optical coherence tomography (SD-OCT) examinations. Longitudinal RNFL measurements were analyzed by linear mixed models incorporating follow-up duration, baseline RNFL thickness, spherical equivalent (SE), age, intraocular pressure, and visual field mean deviation. Thinning rates were classified according to SE into three groups: nonmyopic (NM; >0 D), mild-to-moderately myopic (MM; >-6 D and ≤0 D), and highly myopic (HM; ≤-6 D)., Results: The overall slopes of change in RNFL thickness over time in the NM, MM, and HM groups were -0.305 ± 0.128, -0.294 ± 0.068, and -0.208 ± 0.097  μ m/yr, respectively. Slopes of RNFL thickness changes in these groups were -0.514 ± 0.248, -0.520 ± 0.133, and -0.528 ± 0.188  μ m/yr, respectively. Slopes of RNFL thickness changes in these groups were -0.514 ± 0.248, -0.520 ± 0.133, and -0.528 ± 0.188  μ m/yr, respectively. Slopes of RNFL thickness changes in these groups were -0.514 ± 0.248, -0.520 ± 0.133, and -0.528 ± 0.188  μ m/yr, respectively. Slopes of RNFL thickness changes in these groups were -0.514 ± 0.248, -0.520 ± 0.133, and -0.528 ± 0.188  μ m/yr, respectively. Slopes of RNFL thickness changes in these groups were -0.514 ± 0.248, -0.520 ± 0.133, and -0.528 ± 0.188 ., Conclusions: Refractive error did not affect the physiologic thinning rate of RNFL when assessed by SD OCT., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Daun Jeong et al.)

Computationally predicting reverse intersystem crossing (RISC) rates is important for designing new thermally activated delayed fluorescence (TADF) materials. We report a method that can quantitatively predict RISC rates by explicitly considering the spin-vibronic coupling mechanism. The coupling element of the spin-vibronic Hamiltonian is obtained by expanding the spin-orbit and the non-Born-Oppenheimer terms to second order and is then brought into the Golden Rule rate under the Condon approximation. The rate equation is solved directly in the time domain using a correlation function approach. The contributions of the first-order direct spin-orbit coupling and the second-order spin-vibronic coupling to an RISC rate can be quantitatively analyzed in a separate manner. We demonstrate the utility of the method by applying it to a representative TADF system, where we observe that the spin-vibronic portion is substantial but not dominant especially with a relatively small triplet-singlet energy gap. Likewise, our method may elucidate the physical background of efficient nonradiative transitions from the lowest triplet to a higher lying singlet in other purely organic TADF systems, and it will be of great utility toward designing new such molecules.

Aims: To evaluate the relationship between macular vessel density (mVD) and central visual field sensitivity (cVFS) at different stages of glaucoma and to compare this relationship with that between the thickness of the macular ganglion cell-inner plexiform layer (mGCIPLT) and cVFS., Methods: The mVD and mGCIPLT were measured by optical coherence tomography angiography in 139 patients with glaucoma. The cVFS was defined as the average of 12 central points on 24-2 visual field (VF) testing. Vasculature-function and structure-function relationships were analysed by comparing mVD and mGCIPLT with cVFS in eyes with early and moderate-to-advanced glaucoma., Results: Global and regional mVD-cVFS associations were statistically significant in eyes with moderate-to-advanced (all p<0.05), but not early stage (all p>0.05) glaucoma. The global association between average mVD and cVFS was significantly stronger than that between average mGCIPLT and cVFS in eyes with moderate-to-advanced glaucoma (p=0.049). Reduced mVD was independently associated with cVFS loss after adjusting for age and mGCIPLT in eyes with moderate-to-advanced glaucoma., Conclusions: The macular vasculature-function relationship using mVD was stronger than the structure-function relationship using mGCIPLT in eyes with moderate-to-advanced glaucoma. The mVD may be useful in monitoring cVFS in advanced glaucoma., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

The impact of low muscle mass on pediatric cardiac patients remains unclear. We investigated the impact of low muscle mass on early postoperative outcomes in patients undergoing the Fontan operation. The electronic medical records of 74 patients (aged <18 years) who underwent the Fontan operation were retrospectively reviewed. The cross-sectional areas of the erector spinae and pectoralis muscles were measured using preoperative chest computed tomography (CT), normalized to the body surface area, and combined to obtain the total skeletal muscle index (TSMI). Low muscle mass was defined as a TSMI value lower than the median TSMI for the second quintile. The incidence of major postoperative complications was higher in patients with low muscle mass than in those with high muscle mass (48% (15/31) versus 14% (6/43); P = 0.003). Multivariable analyses revealed that a higher TSMI was associated with a lower likelihood of an increased duration of intensive care unit (>5 days) and hospital stay (>14 days) (odds ratio (OR) 0.86; 95% confidence interval (CI) 0.77-0.96; P = 0.006 and OR 0.92; 95% CI 0.85-0.99; P = 0.035 per 1 cm 2 /m 2 increase in TSMI) and incidence of major postoperative complications (OR 0.90; 95% CI 0.82-0.99; P = 0.039 per 1 cm 2 /m 2 increase in TSMI). Preoperative low muscle mass was associated with poor early postoperative outcomes in pediatric patients undergoing the Fontan operation.

The bioavailable iron is essential for all living organisms, and the dissolution of iron oxide contained in dust and soil is one of the major sources of bioavailable iron in nature. Iodine in the polar atmosphere is related to ozone depletion, mercury oxidation, and cloud condensation nuclei formation. Here we show that the chemical reaction between iron oxides and iodide (I - ) is markedly accelerated to produce bioavailable iron (Fe(II) aq ) and tri-iodide (I 3 - : evaporable in the form of I 2 ) in frozen solution (both with and without light irradiation), while it is negligible in aqueous phase. The freeze-enhanced production of Fe(II) aq and tri-iodide is ascribed to the freeze concentration of iron oxides, iodides, and protons in the ice grain boundaries. The outdoor experiments carried out in midlatitude during a winter day (Pohang, Korea: 36°0' N, 129°19' E) and in an Antarctic environment (King George Island: 62°13' S 58°47' W) also showed the enhanced generation of Fe(II) aq and tri-iodide in ice. This study proposes a previously unknown abiotic mechanism and source of bioavailable iron and active iodine species in the polar environment. The pulse input of bioavailable iron and reactive iodine when ice melts may influence the oceanic primary production and CCN formation.