Genomic and Metabolomic Analyses of Nocardiopsis maritima YSL2 as the Mycorrhizosphere Bacterium of Suaeda maritima (L.) Dumort.

Nine bacteria were isolated from the episphere of Suaeda maritima (L.) Dumort. Among them, the bacterial strain YSL2 displayed the highest antimicrobial activity on agar plates and exhibited significant novelty compared with other bacteria based on 16S rRNA analysis. Consequently, Nocardiopsis maritima YSL2T was subjected to phenotypic characterization and whole-genome sequencing. Phylogenetic analysis revealed its close association with Nocardiopsis aegyptia SNG49T. Furthermore, genomic analysis of strain YSL2T revealed the presence of various gene clusters, indicating its potential for producing antimicrobial secondary metabolites. Upon cultivation on a large scale, maritiamides A and B (1 and 2) were isolated and characterized as cyclic hexapeptides based on nuclear magnetic resonance, ultraviolet, infrared, and mass spectrometric data. The absolute configurations of the amino acid residues in the maritiamides were determined through chiral derivatization, utilizing FDAA and GITC. Maritiamides 1 and 2 exhibited promising antibacterial activities against Staphylococcus epidermidis and weakly inhibited the growth of Escherichia coli and Pseudomonas fluorescens.

The structure of AcrIE4-F7 reveals a common strategy for dual CRISPR inhibition by targeting PAM recognition sites.

Bacteria and archaea use the CRISPR-Cas system to fend off invasions of bacteriophages and foreign plasmids. In response, bacteriophages encode anti-CRISPR (Acr) proteins that potently inhibit host Cas proteins to suppress CRISPR-mediated immunity. AcrIE4-F7, which was isolated from Pseudomonas citronellolis, is a fused form of AcrIE4 and AcrIF7 that inhibits both type I-E and type I-F CRISPR-Cas systems. Here, we determined the structure of AcrIE4-F7 and identified its Cas target proteins. The N-terminal AcrIE4 domain adopts a novel α-helical fold that targets the PAM interaction site of the type I-E Cas8e subunit. The C-terminal AcrIF7 domain exhibits an αß fold like native AcrIF7, which disables target DNA recognition by the PAM interaction site in the type I-F Cas8f subunit. The two Acr domains are connected by a flexible linker that allows prompt docking onto their cognate Cas8 targets. Conserved negative charges in each Acr domain are required for interaction with their Cas8 targets. Our results illustrate a common mechanism by which AcrIE4-F7 inhibits divergent CRISPR-Cas types.

Determination of optimal positive end-expiratory pressure using electrical impedance tomography in infants under general anesthesia: Comparison between supine and prone positions.

AIMS: This study determined the optimal positive end-expiratory pressure levels in infants in supine and prone positions under general anesthesia using electrical impedance tomography (EIT). METHODS: This prospective observational single-centre study included infants scheduled for surgery in the prone position. An electrical impedance tomography sensor was applied after inducing general anesthesia. The optimal positive end-expiratory pressure in the supine position was determined in a decremental trial based on EIT and compliance. Subsequently, the patient's position was changed to prone. Electrical impedance tomography parameters, including global inhomogeneity index, regional ventilation delay, opening pressure, the centre of ventilation, and pendelluft volume, were continuously obtained up to 1 h after prone positioning. The optimal positive end-expiratory pressure in the prone position was similarly determined. RESULTS: Data from 30 infants were analyzed. The mean value of electrical impedance tomography-based optimal positive end-expiratory pressure in the prone position was significantly higher than that in the supine position [10.9 (1.6) cmH2O and 6.1 (0.9) cmH2O, respectively (p < .001)]. Significant differences were observed between electrical impedance tomography- and compliance-based optimal positive end-expiratory pressure. Peak and mean airway, plateau, and driving pressures increased 1 h after prone positioning compared with those in the supine position. In addition, the centre of ventilation for balance in ventilation between the ventral and dorsal regions improved. CONCLUSION: The prone position required higher positive end-expiratory pressure than the supine position in mechanically ventilated infants under general anesthesia. EIT is a promising tool to find the optimal positive end-expiratory pressure, which needs to be individualized.

Ultrasound-guided selective supraclavicular nerve block for postoperative pain control in children receiving Hickman catheter or chemoport insertion: A randomized controlled trial.

BACKGROUND: Optimal pain management after insertion of a central venous catheter in children remains unclear. AIM: This study aimed to evaluate the effects of a selective supraclavicular nerve block on postoperative analgesia in pediatric patients undergoing hickman catheter or chemoport insertion. METHODS: Fifty patients aged 3-18 years scheduled for elective Hickman or chemoport insertion were randomized into two groups of 25 each: one group received an ultrasound-guided selective supraclavicular nerve block with 0.1 mL/kg of 0.5% ropivacaine (SSCNB group), and the other group did not receive a nerve block (control group). The primary outcome was the postoperative Wong-Baker Faces Pain Rating Scale score measured between 10 and 30 min after surgery. Secondary outcomes included pain scores at 1, 3, and 24 h after the surgery, block-related complications, length of stay in the postanesthesia care unit, postoperative analgesic consumption, and time to first analgesic use 24 h after surgery. RESULTS: The worst pain score within 30 min in the recovery room was significantly lower in the SSCNB group compared to the control group (6 [5-7] vs. 3 [2-4]; median difference, -3; 95% CI, -4 to -1; p < .001). Pain scores at 1, 3, and 24 h after surgery were also significantly lower in the SSCNB group. The need for both opioid and non-opioid analgesics in the postoperative period was significantly lower in the SSCNB group (36.0% vs. 0%; p = .002 and 44.0% vs. 16.0%; mean difference, -28%; 95% CI, -56 to 0.19; p = .033, respectively), while other secondary outcomes were not significantly different between the two groups. CONCLUSIONS: Ultrasound-guided SSCNB is an effective method for managing postoperative pain in children undergoing Hickman catheter or chemoport insertion, reducing the need for analgesics within 24 h after surgery.

Atmospheric particulate matter and hypoxaemia in Korean children receiving general anaesthesia: A retrospective analysis.

BACKGROUND: The association between the concentration of atmospheric particulate matter on the day of surgery and the occurrence of intra-operative hypoxaemia in children receiving general anaesthesia is unclear. OBJECTIVE: To investigate the association between the exposure to of particulate matter on the day of surgery and the occurrence of intra-operative hypoxaemia, defined as a pulse oximetry oxygen saturation of less than 90% for more than 1 min, in children. DESIGN: Retrospective study. SETTING: Single-centre. PARTICIPANTS: Children aged 18 years or younger who received general anaesthesia between January 2019 and October 2020. INTERVENTION: Information on daily levels of particulate matter with a diameter 10 µm or less and 2.5 µm or less measured within a neighbourhood corresponding to the area defined by the hospital's zip code was obtained from publicly available air-quality data. MAIN OUTCOME MEASURES: The primary outcome was intra-operative hypoxaemia, defined as a pulse oximetry oxygen saturation of less than 90% lasting for more than 1 min, manually verified by anaesthesiologists using vital sign registry data extracted at 2 s intervals. RESULTS: Of the patients finally analysed, 3.85% (489/13 175) experienced intra-operative hypoxaemia. Higher levels of particulate matter 10 µm or less in diameter (≥81 µg m-3, 472/12 900, 3.7%) were associated with an increased occurrence of intra-operative hypoxaemia compared with lower particulate matter concentrations [<81 µg m-3, 17/275, 6.2%; adjusted odds ratio, 1.71; 95% confidence interval (CI), 1.04 to 2.83; P = 0.035]. CONCLUSION: The level of particulate matter on the day of surgery pose a risk of intra-operative hypoxaemia in children receiving general anaesthesia. If the concentrations of particulate matter 10 µm or less in diameter on the day of surgery are high, children receiving general anaesthesia should be managed with increased caution.

Effectiveness of head-mounted ultrasound display for radial arterial catheterisation in paediatric patients by anaesthesiology trainees: A randomised clinical trial.

BACKGROUND: The effectiveness of head mounted real-time ultrasound displays (hereafter referred to as 'smart glasses') in improving hand-eye coordination in less experienced individuals, such as trainees in anaesthesia, is unclear. OBJECTIVES: To compare the first-attempt success rate of smart glasses-assisted ultrasound-guided paediatric radial artery catheterisation with conventional ultrasound guided catheterisation performed by anaesthesiology trainees. DESIGN: Prospective randomised controlled trial. SETTINGS: Tertiary university hospital from September 2021 to February 2023. PATIENTS: One hundred and twenty-two paediatric patients (age <7 years, weight ≥3 kg) who required radial artery cannulation during general anaesthesia. INTERVENTIONS: The participants were randomly assigned to either the ultrasound screen group (control) or the smart glasses group prior to radial artery catheterisation. MAIN OUTCOME MEASURES: The primary outcome was the first attempt success rate. Secondary outcomes included the number of attempts, use of transfixion technique, overall complication rate, and clinical anaesthesiology (CA) year of the operators. RESULTS: A total of 119 paediatric patients were included in the analysis. The smart glasses group exhibited higher first-attempt success rate than did the control group (89.8% [53/59] vs. 71.7% [43/60]; P  = 0.023; odds ratio (OR) 3.49; (95% confidence interval (CI) 1.27-9.6). The overall number of attempts [median, 1; interquartile range (IQR), 1-1; range, 1-3 vs. median, 1; IQR, 1-2; range, 1-4; P   =  0.006], use of transfixion technique (12/59 [20.3%] vs. 28/60 [46.7%]; P  = 0.002), and overall complication rate (6.8% [4/59] vs. 30.0% [18/60]; P  = 0.002) were lower in the smart glasses group than in the control group. However, among paediatric anaesthesiology fellows (CA 5 years), the first- (89.3% [25/28] vs. 80.8% [21/26]; P  = 0.619) and second-attempt success rates (96.4% [27/28] vs. 80.8% [21/26]; P  = 0.163) did not differ between the two groups. CONCLUSIONS: Smart glasses-assisted ultrasound guided radial artery catheterisation improved the first attempt success rate among anaesthesiology trainees, reducing the number of attempts and overall complication rates in small paediatric patients. Smart glasses were more effective for anaesthesia residents (CA 2-4 years) but were not effective for paediatric anaesthesiology fellows (CA 5 years). TRIAL REGISTRATION: ClinicalTrials.gov (NCT05030649) ( https://classic.clinicaltrials.gov/ct2/show/NCT05030649 ).

Effects of goal-directed analgesia using the analgesia nociception index in children undergoing surgery for moyamoya disease: A randomised controlled trial.

BACKGROUND: The potential benefits of Analgesia Nociception Index guided intra-operative analgesia on intra-operative opioid consumption remains to be demonstrated in paediatric anaesthesia. OBJECTIVES: This study aimed to explore the effects of Analgesia Nociception Index guided analgesia on sufentanil consumption during anaesthesia and postoperative pain scores in paediatric patients with moyamoya disease. DESIGN: A prospective randomised controlled study. SETTING: Seoul National University Children's Hospital, Seoul, Republic of Korea. PATIENTS: A total of 40 children scheduled for encephaloduroarteriosynangiosis. MAIN OUTCOME MEASURES: The primary outcome was total intra-operative sufentanil consumption, and the secondary outcomes included postoperative pain scores and incidence of opioid-related adverse events. RESULTS: The Analgesia Nociception Index group showed lower intra-operative sufentanil consumption (in µg kg-1 h-1) compared with the Standard group (0.30 ±â€Š0.12 and 0.39 ±â€Š0.17, respectively; mean difference, -0.09; 95% confidence interval, -0.19 to 0.00; P = 0.049). Postoperatively, compared with the Standard group, the Analgesia Nociception Index group reported lower median pain scores at 18 and 24 h and maximum pain within 24 h (1 [0 to 2] vs. 3 [2 to 5]; P = 0.004, 1 [0 to 2] vs. 3 [1 to 4]; P = 0.041, and 4 [3 to 5] vs. 5 [4 to 7]; P = 0.045, respectively), with fewer patients experiencing nausea (3 [15%] vs. 10 [50%], P = 0.043). CONCLUSION: The Analgesia Nociception Index guided analgesic protocol can reduce intra-operative sufentanil consumption and postoperative pain within 24 h with fewer nausea symptoms in paediatric patients with moyamoya disease who undergo encephaloduroarteriosynangiosis. TRIAL REGISTRATION NUMBER: NCT05672212 (registered at clinicaltrials, principal investigator: K.E.H., registration date: 2 January 2023).

Isolation of New Diterpenoids from the Halophyte, Vitex rotundifolia, and their Antioxidant and Anti-inflammatory Activities.

In this study, three diterpenoids (1-3), including one known compound (1), were isolated from the fruits of Vitex rotundifolia and their structures were determined via spectroscopic analysis. In lipopolysaccharide-stimulated RAW264.7 cells, these compounds dose-dependently decreased the intracellular reactive oxygen species levels and nitric oxide production compared to those in the control cells. At 25 µM/mL, these compounds also diminished the protein expression of the pro-inflammatory cytokines, inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-6, with compound 3 exhibiting the most potent inhibitory effect.

Machine Learning-Based Etiologic Subtyping of Ischemic Stroke Using Circulating Exosomal microRNAs.

Ischemic stroke is a major cause of mortality worldwide. Proper etiological subtyping of ischemic stroke is crucial for tailoring treatment strategies. This study explored the utility of circulating microRNAs encapsulated in extracellular vesicles (EV-miRNAs) to distinguish the following ischemic stroke subtypes: large artery atherosclerosis (LAA), cardioembolic stroke (CES), and small artery occlusion (SAO). Using next-generation sequencing (NGS) and machine-learning techniques, we identified differentially expressed miRNAs (DEMs) associated with each subtype. Through patient selection and diagnostic evaluation, a cohort of 70 patients with acute ischemic stroke was classified: 24 in the LAA group, 24 in the SAO group, and 22 in the CES group. Our findings revealed distinct EV-miRNA profiles among the groups, suggesting their potential as diagnostic markers. Machine-learning models, particularly logistic regression models, exhibited a high diagnostic accuracy of 92% for subtype discrimination. The collective influence of multiple miRNAs was more crucial than that of individual miRNAs. Additionally, bioinformatics analyses have elucidated the functional implications of DEMs in stroke pathophysiology, offering insights into the underlying mechanisms. Despite limitations like sample size constraints and retrospective design, our study underscores the promise of EV-miRNAs coupled with machine learning for ischemic stroke subtype classification. Further investigations are warranted to validate the clinical utility of the identified EV-miRNA biomarkers in stroke patients.

LIN28A loss of function is associated with Parkinson's disease pathogenesis.

Parkinson's disease (PD) is neurodegenerative movement disorder characterized by degeneration of midbrain-type dopamine (mDA) neurons in the substantia nigra (SN). The RNA-binding protein Lin28 plays a role in neuronal stem cell development and neuronal differentiation. In this study, we reveal that Lin28 conditional knockout (cKO) mice show degeneration of mDA neurons in the SN, as well as PD-related behavioral deficits. We identify a loss-of-function variant of LIN28A (R192G substitution) in two early-onset PD patients. Using an isogenic human embryonic stem cell (hESC)/human induced pluripotent stem cell (hiPSC)-based disease model, we find that the Lin28 R192G variant leads to developmental defects and PD-related phenotypes in mDA neuronal cells that can be rescued by expression of wild-type Lin28A. Cell transplantation experiments in PD model rats show that correction of the LIN28A variant in the donor patient (pt)-hiPSCs leads to improved behavioral phenotypes. Our data link LIN28A to PD pathogenesis and suggest future personalized medicine targeting this variant in patients.

Effect of Tulobuterol Patch Versus Placebo on the Occurrence of Respiratory Adverse Events in Children Undergoing Tonsillectomies: A Randomized Controlled Trial.

BACKGROUND: Perioperative respiratory adverse events are common in children. We aimed to evaluate the effect of the transdermal ß-2 agonist, tulobuterol, compared with that of placebo on the incidence of perioperative respiratory adverse events in pediatric patients undergoing tonsillectomy. METHODS: In this triple-blinded (patient, anesthesia provider, and outcome assessor) randomized controlled trial, 188 patients were randomly allocated to receive tulobuterol or a placebo. The tulobuterol groups received a tulobuterol patch (1 mg) masked with a bandage, whereas the placebo only received the bandage. The assigned bandage was applied to the patients 8 to 10 hours before the surgery. The primary outcome was the occurrence of any perioperative respiratory adverse events: oxygen desaturation <95%, airway obstruction, laryngospasm, bronchospasm, severe coughing, or stridor. The outcomes were evaluated using the average relative effect test, which estimates the effect of individual components of a composite outcome and then averages effects across components. RESULTS: A total of 88 and 94 patients who received tulobuterol and placebo, respectively, were analyzed. The incidence of any perioperative respiratory adverse event was lower with tulobuterol (n = 13/88; 14.7%) than that with the placebo (n = 40/94; 42.5%), with an estimated average relative risk (95% confidence interval) across components of 0.35 (0.20-0.60; P < .001). The symptoms of airway obstruction were lower with tulobuterol (n = 8/88; 9.0%) than that with the placebo (n = 32/94; 34.0%), with relative risk (95% CI) of 0.31 (0.17-0.56; P < .001). The occurrence of severe coughing was lower with tulobuterol (n = 1/88; 1.1%) than that with the placebo (n = 8/94; 8.5%), with relative risk (95% CI) of 0.15 (0.03-0.68; P = .014). CONCLUSIONS: In preschool children undergoing tonsillectomy, the preoperative application of a tulobuterol patch could decrease the occurrence of perioperative respiratory adverse events. Further studies are needed to elucidate the effect of the tulobuterol patch in a broad spectrum of pediatric anesthesia.

Higher portal venous pulsatility is associated with worse clinical outcomes following congenital heart surgery: a single-centre prospective cohort study.

PURPOSE: Increased portal venous flow pulsatility is associated with major complications after adult cardiac surgery. Nevertheless, no data are available for pediatric patients with congenital heart disease. We hypothesized that Doppler parameters including portal flow pulsatility could be associated with postoperative outcomes in children undergoing various cardiac surgeries. METHODS: We conducted a prospective observational cohort study in children undergoing congenital cardiac surgery. We obtained postoperative portal, splenic, and hepatic venous Doppler data and perioperative clinical data including major postoperative complications. Portal and splenic venous flow pulsatility were calculated. We evaluated the association between venous Doppler parameters and adverse outcomes. The primary objective was to determine whether postoperative portal flow pulsatility could indicate major complications following congenital heart surgery. RESULTS: In this study, we enrolled 389 children, 74 of whom experienced major postoperative complications. The mean (standard deviation) portal pulsatility (44 [30]% vs 25 [14]%; 95% confidence interval [CI] for mean difference, 12 to 26; P < 0.001] and splenic pulsatility indices (41 [30]% vs 26 [16]%; 95% CI, 7 to 23; P < 0.001) were significantly higher in children with postoperative complications than in those without complications. The portal pulsatility index was able to help identify postoperative complications in biventricular patients and univentricular patients receiving bidirectional cavopulmonary shunt whereas it did not in other univentricular patients. An increased postoperative portal pulsatility index was significantly associated with major complications after pediatric cardiac surgery (odds ratio, 1.40; 95% CI, 1.29 to 1.91; P < 0.001). CONCLUSIONS: Higher portal venous pulsatility is associated with major postoperative complications in children undergoing cardiac surgery. Nevertheless, more data are needed to conclude the efficacy of portal venous pulsatility in patients with univentricular physiology. STUDY REGISTRATION: ClinicalTrials.gov (NCT03990779); registered 19 June 2019.

RéSUMé: OBJECTIF: L'augmentation de la pulsatilité du flux de la veine porte est associée à des complications majeures après une chirurgie cardiaque chez l'adulte. Néanmoins, aucune donnée n'est disponible pour la patientèle pédiatrique atteinte de cardiopathie congénitale. Nous avons émis l'hypothèse que les paramètres Doppler, y compris la pulsatilité du flux de la veine porte, pourraient être associés aux devenirs postopératoires des enfants bénéficiant de diverses chirurgies cardiaques. MéTHODE: Nous avons réalisé une étude de cohorte observationnelle prospective portant sur des enfants bénéficiant d'une chirurgie cardiaque congénitale. Nous avons obtenu des données Doppler des veines porte, spléniques et hépatiques postopératoires ainsi que des données cliniques périopératoires, y compris les complications postopératoires majeures. La pulsatilité du flux des veines porte et spléniques a été calculée. Nous avons évalué l'association entre les paramètres Doppler veineux et les issues indésirables. L'objectif principal était de déterminer si la pulsatilité du flux postopératoire de la veine porte pouvait constituer un indicateur des complications majeures après une chirurgie cardiaque congénitale. RéSULTATS: Dans cette étude, nous avons recruté 389 enfants, dont 74 ont présenté des complications postopératoires majeures. La pulsatilité moyenne de la veine porte (écart type) (44 [30] % vs 25 [14] %; intervalle de confiance [IC] à 95 % pour la différence moyenne, 12 à 26; P < 0,001] et les indices de pulsatilité splénique (41 [30] % vs 26 [16] %; IC 95 %, 7 à 23; P < 0,001) étaient significativement plus élevés chez les enfants présentant des complications postopératoires que chez les enfants sans complications. L'indice de pulsatilité de la veine porte a permis d'identifier les complications postopératoires chez les patient·es biventriculaires et les patient·es univentriculaires recevant une anastomose cavo-pulmonaire bidirectionnelle (procédure de Glenn), alors que ce n'était pas le cas chez les autres patient·es univentriculaires. Une augmentation postopératoire de l'indice de pulsatilité de la veine porte était significativement associée à des complications majeures après une chirurgie cardiaque pédiatrique (rapport de cotes, 1,40; IC 95 %, 1,29 à 1,91; P < 0,001). CONCLUSION: Une pulsatilité plus élevée de la veine porte est associée à des complications postopératoires majeures chez les enfants bénéficiant d'une chirurgie cardiaque. Néanmoins, davantage de données sont nécessaires pour conclure à l'efficacité de la pulsatilité de la veine porte chez les patient·es présentant une physiologie univentriculaire. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT03990779); enregistrée le 19 juin 2019.

Evaluation of Portal, Splenic, and Hepatic Vein Flows in Children Undergoing Congenital Heart Surgery.

OBJECTIVE: Little is known about changes in portal, splenic, and hepatic vein flow patterns in children undergoing congenital heart surgery. This study aimed to determine the characteristics of portal, splenic, and hepatic vein flow patterns using ultrasonography in children undergoing cardiac surgery. DESIGN: Single-center, prospective observational study. SETTING: Tertiary children's hospital, operating room. PARTICIPANTS: Children undergoing cardiac surgery. MEASUREMENT AND MAIN RESULTS: The authors obtained ultrasound data from the heart, inferior vena cava, portal, splenic, and hepatic veins before and after surgeries. In the biventricular group, which included children with atrial and ventricular septal defects and pulmonary stenosis (n = 246), the portal pulsatility index decreased from 38.7% to 25.6% (p < 0.001) after surgery. The preoperative portal pulsatility index was significantly higher in patients with pulmonary hypertension (43.3% v 27.4%; p < 0.001). In the single-ventricle group (n = 77), maximum portal vein flow velocities of Fontan patients were significantly lower (13.5 cm/s) compared with that of patients with modified Blalock-Taussig shunt (19.7 cm/s; p = 0.035) or bidirectional cavopulmonary shunt (23.1 cm/s; p < 0.001). The cardiac index was inversely correlated with the portal pulsatility index in the bidirectional cavopulmonary shunt and Fontan circulation. (ß = -5.693, r2 = 0.473; p = 0.001) The portal pulsatility index was correlated with splenic venous pulsatility and hepatic venous atrial reverse flow velocity in biventricular and single-ventricle groups. CONCLUSIONS: The characteristics of venous Doppler patterns in the portal, splenic, and hepatic veins differed according to congenital heart disease. Further studies are required to determine the association between splanchnic venous Doppler findings and clinical outcomes in this population.

Comparison of effects of volatile and intravenous anesthetics on pupillary function during general anesthesia in children: A prospective observational study.

BACKGROUND: The light reflex, which reflects central nervous system dysfunction, can also be affected by anesthetic agents. AIMS: We evaluated whether these effects differed according to the anesthetic agent in pediatric patients. METHODS: Twenty children aged 3-12 years who were scheduled to undergo elective surgery under general anesthesia were randomly allocated to propofol and sevoflurane groups and underwent pupillometric assessments at five points during anesthesia: T1, after confirming loss of consciousness; T2, after endotracheal intubation; T3, at the time of skin incision; T4, 1 h after skin incision; and T5, before endotracheal extubation. The primary outcome was the Neurological Pupil index at T4, and the secondary outcomes were other pupillometric parameters, including pupil diameter, percentage of change in pupil diameter, dilation velocity, and constriction velocity. RESULTS: At T4, the Neurological Pupil index was significantly lower in the sevoflurane group (median difference, 0.30; 95% CI, 0.00 to 0.70; p = .036). Furthermore, the Neurological Pupil index at all time points was lower in the sevoflurane group. The time-and-group interaction effects on constriction velocity and dilation velocity were significantly different [F(1, 4) = 16.68, p = .002; F(1, 4) = 14.78, p = .008, respectively] but were not different on the Neurological Pupil index, pupil diameter, and percentage of change in pupil diameter. No intergroup differences were observed in the baseline characteristics, the flow rate of remifentanil at each time point, and total infused remifentanil. CONCLUSION: The Neurological Pupil index value in pediatric patients under general anesthesia is affected by the anesthetic agent used; this factor requires consideration in evaluations of the Neurological Pupil index during general anesthesia.

Pharmacokinetics of dexmedetomidine in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass can affect the pharmacokinetics of anesthetic agents. AIMS: We aimed to evaluate the pharmacokinetics of dexmedetomidine for infants and small children undergoing cardiac surgery with cardiopulmonary bypass based on population pharmacokinetics. METHODS: We enrolled 30 pediatric cardiac surgical patients in this study. After anesthetic induction with atropine (0.02 mg/kg), thiopental sodium (5 mg/kg), and fentanyl (2-3 µg/kg), we administered 1 µg/kg of dexmedetomidine for 10 min, followed by administration of 0.5 µg/kg of dexmedetomidine per hour during surgery. At the initiation of cardiopulmonary bypass, 1 µg/kg of dexmedetomidine was infused over 5 min. Arterial blood was obtained at predefined time points. A pharmacokinetic model was developed using NONMEM. Theory-based allometric scaling with fixed exponents was applied. Weight, age, post-menstrual age, fat-free mass, whether to implement cardiopulmonary bypass and temperature were explored as covariates. RESULTS: A total of 376 blood samples were obtained from 29 children (age: 20.3 ± 19.3 months, weight: 9.7 ± 4.1 kg). A two-compartment mammillary model with third compartment associated cardiopulmonary bypass procedure best explained the pharmacokinetics of dexmedetomidine. The pharmacokinetic parameter estimates (95% CI) standardized to a 70-kg person were as follows: V1 (L) = 31.6 (17.9-39.5), V2 (L) = 90.1 (44.0-330), Cl (L/min) = 1.08 (0.70-1.25), Q (L/min) = 2.0 (1.05-3.46). Volume for third compartment associated cardiopulmonary bypass procedure (L) = 39.4 (19.3-50.9). Clearance was not influenced by the presence of cardiopulmonary bypass in this model. CONCLUSION: When cardiopulmonary bypass is applied, the plasma concentration of dexmedetomidine decreases due to an increase in the volume of distribution, so a loading dose is required to maintain the previous concentration.

Effect of tidal volume change on pressure-based prediction of fluid responsiveness in children.

INTRODUCTION: It is known that pulse pressure variation and systolic pressure variation cannot predict fluid responsiveness in children. In adults, the ability of these dynamic parameters to predict fluid responsiveness is improved by increasing tidal volume. We planned to investigate whether pulse pressure variation or systolic pressure variation can predict fluid responsiveness in children when augmented by increasing tidal volume by conducting a prospective study. METHODS: We enrolled children younger than 7 years who underwent cardiac surgery for atrial septal defect or ventricular septal defect. After sternum closure, pulse pressure variation and systolic pressure variation were continuously recorded while changing the tidal volume to 6, 10, and 14 mL/kg. Fluid loading was done with 10 mL/kg of crystalloids for 10 min, and stroke volume index was measured via transesophageal echocardiography. Children whose stroke volume index increased by more than 15% after the fluid loading were defined as responders to fluid therapy. We set primary outcome as the predictability of pulse pressure variation and systolic pressure variation for fluid responsiveness and measured the area under the curve of receiver operating characteristics curve. RESULTS: Twenty-six children were included, of which 15 were responders. At the tidal volume of 14 mL/kg, the area under the curves of receiver operating characteristics curves of pulse pressure variation and systolic pressure variation were 0.576 (p = .517) and 0.548 (p = .678), respectively. The differences in dynamic parameters between responders and nonresponders were not significant. DISCUSSION: Failure of pulse pressure variation or systolic pressure variation at augmented tidal volume in children may be due to difference in their arterial compliance from those of adults. Large compliance of thoracic wall may be another reason. CONCLUSIONS: Augmented pulse pressure variation or systolic pressure variation due to increased tidal volume cannot predict fluid responsiveness in children after simple cardiac surgery.

Perioperative Respiratory-Adverse Events Following General Anesthesia Among Pediatric Patients After COVID-19.

BACKGROUND: The perianesthetic morbidity, mortality risk and anesthesia-associated risk after preoperative coronavirus disease 2019 (COVID-19) omicron variant in pediatric patients have not been fully demonstrated. We examined the association between preoperative COVID-19 omicron diagnosis and the incidence of overall perioperative adverse events in pediatric patients who received general anesthesia. METHODS: This retrospective study included patients aged < 18 years who received general anesthesia between February 1 and June 10, 2022, in a single tertiary pediatric hospital. They were divided into two groups; patients in a COVID-19 group were matched to patients in a non-COVID-19 group during the omicron-predominant period in Korea. Data on patient characteristics, anesthesia records, post-anesthesia records, COVID-19-related history, symptoms, and mortality were collected. The primary outcomes were the overall perioperative adverse events, including perioperative respiratory adverse events (PRAEs), escalation of care, and mortality. RESULTS: In total, 992 patients were included in the data analysis (n = 496, COVID-19; n = 496, non-COVID-19) after matching. The overall incidence of perioperative adverse events was significantly higher in the COVID-19 group than in the non-COVID-19 group (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.89-1.94). The difference was significant for PRAEs (OR, 2.00; 95% CI, 1.96-2.02) but not in escalation of care or mortality. The most pronounced difference between the two groups was observed in instances of high peak inspiratory pressure ≥ 25 cmH2O during the intraoperative period (OR, 11.0; 95% CI, 10.5-11.4). Compared with the non-COVID-19 group, the risk of overall perioperative adverse events was higher in the COVID-19 group diagnosed 0-2 weeks before anesthesia (OR, 6.5; 95% CI, 2.1-20.4) or symptomatic on the anesthesia day (OR, 6.4; 95% CI, 3.30-12.4). CONCLUSION: Pediatric patients with the preoperative COVID-19 omicron variant had increased risk of PRAEs. Patients within 2 weeks after COVID-19 or those with symptoms had a higher risk of PRAEs.

Clinical-Scale Mesenchymal Stem Cell-Derived Extracellular Vesicle Therapy for Wound Healing.

We developed an extracellular vesicle (EV) bioprocessing platform for the scalable production of human Wharton's jelly mesenchymal stem cell (MSC)-derived EVs. The effects of clinical-scale MSC-EV products on wound healing were tested in two different wound models: subcutaneous injection of EVs in a conventional full-thickness rat model and topical application of EVs using a sterile re-absorbable gelatin sponge in the chamber mouse model that was developed to prevent the contraction of wound areas. In vivo efficacy tests showed that treatment with MSC-EVs improved the recovery following wound injury, regardless of the type of wound model or mode of treatment. In vitro mechanistic studies using multiple cell lines involved in wound healing showed that EV therapy contributed to all stages of wound healing, such as anti-inflammation and proliferation/migration of keratinocytes, fibroblasts, and endothelial cells, to enhance wound re-epithelialization, extracellular matrix remodeling, and angiogenesis.

Circulating Extracellular Vesicles in Stroke Patients Treated With Mesenchymal Stem Cells: A Biomarker Analysis of a Randomized Trial.

BACKGROUND: Mesenchymal stem cells (MSCs) secrete trophic factors and extracellular vesicles (EVs). However, the level and role of EVs after MSC therapy in patients with stroke are unknown. We investigated whether circulating EVs and trophic factors are increased after MSCs and are related to the therapeutic benefits in the STARTING-2 trial (Stem Cell Application Researches and Trials in Neurology-2) participants. METHODS: In this prospective randomized controlled trial, patients with chronic major stroke were assigned, in a 2:1 ratio, to receive autologous MSC intravenous injection (MSC group, n=39) or standard treatment (control group, n=15) and followed for 3 months. Detailed clinical assessment and neuroplasticity on diffusion tensor image and resting-state functional magnetic resonance imaging were evaluated. Serial samples were collected, before/after MSCs therapy. The primary outcome measure was circulating factors that are associated with the clinical improvement in the Fugl-Meyer Assessment (secondary end point of the trial) and neuroplasticity on diffusion tensor image and resting-state functional magnetic resonance imaging. Additional outcome measures were microRNAs and trophic factors enriched in the plasma EVs, obtained using quantitative polymerase chain reaction and ELISA, respectively. RESULTS: Circulating EV levels were increased ≈5-fold (mean±SD, from 2.7×109±2.2×109 to 1.3×1010±1.7×1010 EVs/mL) within 24 hours after injection of MSCs (P=0.001). After adjustment of age, sex, baseline stroke severity, and the time interval from stroke onset to treatment, only the EV number was independently associated with improvement in motor function (odds ratio, 5.718 for EV numberLog [95% CI, 1.144-28.589]; P=0.034). Diffusion tensor image and resting-state functional magnetic resonance imaging showed that integrity of the ipsilesional corticospinal tract and intrahemispheric motor network were significantly correlated with circulating EV levels, respectively (P<0.05). MicroRNAs related to neurogenesis/neuroplasticity (eg, microRNA-18a-5p) were significantly increased in circulating EVs after MSC therapy (P=0.0479). In contrast, trophic factor levels were not changed after MSC therapy. CONCLUSIONS: This trial is the first to show that treatment of ischemic stroke patients with MSCs significantly increases circulating EVs, which were significantly correlated with improvement in motor function and magnetic resonance imaging indices of plasticity. REGISTRATION: URL: https://www. CLINICAL TRIALS: gov; Unique identifier: NCT01716481.

Association between type 2 diabetes and skeletal muscle quality assessed by abdominal computed tomography scan.

AIM: To examine the association between type 2 diabetes and the amount and quality of trunk muscle as assessed by computed tomography (CT) scan. MATERIALS AND METHODS: A total of 20,986 subjects (13,007 men and 7979 women) who underwent abdominal CT scan as part of a routine health check-up were included. The total abdominal muscle area (TAMA) measured at the third lumbar vertebrae was classified into skeletal muscle area (SMA), and intermuscular adipose tissue area. SMA was divided into good quality muscles (normal attenuation muscle area [NAMA]) and poor quality muscles (low attenuation muscle area). NAMA/TAMA index was calculated. RESULTS: Subjects with type 2 diabetes had higher values of TAMA and SMA but significantly lower values of NAMA and NAMA/TAMA index. Compared with those in the lowest quartile of NAMA/TAMA index, subjects in the highest quartile had metabolically favourable laboratory findings, a lower prevalence of type 2 diabetes (Q1 vs. Q4: 19.3% vs. 9.5% in men, 12.3% vs. 3.0% in women) and inverse association with type 2 diabetes (odds ratio for Q2, Q3, and Q4: 0.87, 0.78, and 0.75 in men; 0.82, 0.70, and 0.68 in women) after multivariable adjustment. CONCLUSIONS: The amount of good quality muscle on CT scan was associated with a lower prevalence of type 2 diabetes.