Optimal dose of normal saline for confirming correct peripheral venous access with precordial Doppler ultrasonography in children.

Precordial Doppler ultrasound technology can be utilized to confirm correct peripheral intravenous vascular (PIV) access in children during surgery. This study aimed to determine the minimally required dose of normal saline (NS) for confirming correct PIV access. Healthy children were randomly allocated to receive a 0.1 mL/kg, 0.3 mL/kg, or 0.5 mL/kg dose of NS injected via PIV access. Two independent raters judged the change in the recorded precordial Doppler sound test (S-test) before and after NS injection. Typically, rapid injection of NS increased the pitch of the heartbeat as the injection volume increased. Changes in blood flow velocity test (V-test) results were evaluated using a cut-off value of 1 cm/s. Both in the S- and V-tests, the detection rate of correct PIV access was lower with 0.1 mL/kg NS than with 0.3 mL/kg or 0.5 mL/kg. Logistic regression analysis showed that the positive results in both the S- and V-tests were significantly decreased with a 0.1 mL/kg NS; no significant difference was observed with a 0.3 mL/kg NS (reference dose: 0.5 mL/kg). These results suggest 0.3 mL/kg is the minimally required dose of NS for confirming correct PIV access. This study is registered with the University Hospital Medical Information Network (UMIN000041330).

Optimal probe position for precordial Doppler ultrasound in children.

BACKGROUND: Precordial Doppler ultrasound technology can be used to confirm correct peripheral intravenous access in children. Changes in precordial Doppler sound from the baseline after injecting normal saline are detected using a correct peripheral intravenous access. However, the location of the precordial Doppler probe has been inconsistent in previous studies. Our study aimed to determine whether the right or left parasternal border is the optimal location for precordial Doppler probe placement. METHODS: This single-center, prospective interventional study was conducted between July 2021 and January 2022 and included children aged 1-6 years. The Doppler probe was placed under general anesthesia at the most audible site on the right and left parasternal borders of patients. Baseline heartbeat was recorded by the Doppler for 10 s on the right and left parasternal borders. After randomizing the order of the recorded data, two blinded raters separately listened to the data and decided the audibility of the sounds. RESULTS: A total of 77 patients were enrolled in the study. The proportion of the audible baseline heartbeat was significantly higher on the left parasternal borders than on the right by both rater 1 (96.1%, 22.1%, p < 0.001) and rater 2 (96.1%, 27.3%, p < 0.001). Regarding inter-rater reproducibility, Cohen's kappa statistics for the left and right parasternal borders were significant (0.65 and 0.79, both p < 0.001). CONCLUSIONS: The baseline heartbeat was more audible on the left parasternal border than on the right parasternal border with acceptably high interrater reproducibility. This is inconsistent with the interpretations of previous reports.

Sedation with dexmedetomidine and propofol in children with Fontan circulation undergoing cardiac catheterization: A descriptive study.

Background: A combination of dexmedetomidine and propofol is considered advantageous for maintaining spontaneous breathing with a satisfactory depth of anesthesia. However, the incidence of upper airway obstruction under sedation with dexmedetomidine and propofol in patients with Fontan circulation remains unanswered. This study aimed to evaluate upper airway patency and oxygen desaturation during sedation with dexmedetomidine and propofol for cardiac catheterization in pediatric patients with Fontan circulation. Methods: In this descriptive study, we reviewed medical records of patients with Fontan circulation who underwent cardiac catheterization between December 2018 and August 2020 at a single-center 200-bed academic children's hospital in Japan. Results: A total of 35 patients with Fontan circulation sedated with a departmental protocol of dexmedetomidine and propofol infusion for cardiac catheterization were reviewed. Overall, the incidence of airway interventions and oxygen desaturation were 31.4% and 28.6%, respectively. In children with a history of snoring and additional use of intravenous midazolam, the rates of airway interventions were 50% and 100%, respectively. In patients ≤2 years old with recent upper respiratory infection (URI) symptoms, oxygen desaturation rate was 75%. Conclusions: In children with Fontan circulation, the incidence rate of upper airway obstruction was high under sedation with dexmedetomidine and propofol during cardiac catheterization, which is commonly considered safe in children without Fontan circulation. A history of snoring, an additional bolus of IV midazolam, and the presence of recent URI symptoms in patients ≤2 years old are potential risks for upper airway obstruction.

Selective translation of epigenetic modifiers affects the temporal pattern and differentiation of neural stem cells.

The cerebral cortex is formed by diverse neurons generated sequentially from neural stem cells (NSCs). A clock mechanism has been suggested to underlie the temporal progression of NSCs, which is mainly defined by the transcriptome and the epigenetic state. However, what drives such a developmental clock remains elusive. We show that translational control of histone H3 trimethylation in Lys27 (H3K27me3) modifiers is part of this clock. We find that depletion of Fbl, an rRNA methyltransferase, reduces translation of both Ezh2 methyltransferase and Kdm6b demethylase of H3K27me3 and delays the progression of the NSC state. These defects are partially phenocopied by simultaneous inhibition of H3K27me3 methyltransferase and demethylase, indicating the role of Fbl in the genome-wide H3K27me3 pattern. Therefore, we propose that Fbl drives the intrinsic clock through the translational enhancement of the H3K27me3 modifiers that predominantly define the NSC state.

Model difference in the effect of cilostazol on the development of experimental pulmonary hypertension in rats.

BACKGROUND: Preventing pulmonary vascular remodeling is a key strategy for pulmonary hypertension (PH). Causes of PH include pulmonary vasoconstriction and inflammation. This study aimed to determine whether cilostazol (CLZ), a phosphodiesterase-3 inhibitor, prevents monocrotaline (MCT)- and chronic hypoxia (CH)-induced PH development in rats. METHODS: Fifty-one male Sprague-Dawley rats were fed rat chow with (0.3% CLZ) or without CLZ for 21 days after a single injection of MCT (60 mg/kg) or saline. Forty-eight rats were fed rat chow with and without CLZ for 14 days under ambient or hypobaric (air at 380 mmHg) CH exposure. The mean pulmonary artery pressure (mPAP), the right ventricle weight-to-left ventricle + septum weight ratio (RV/LV + S), percentages of muscularized peripheral pulmonary arteries (%Muscularization) and medial wall thickness of small muscular arteries (%MWT) were assessed. Levels of the endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (peNOS), AKT, pAKT and IκB proteins in lung tissue were measured using Western blotting. Monocyte chemotactic protein (MCP)-1 mRNA in lung tissue was also assessed. RESULTS: mPAP [35.1 ± 1.7 mmHg (MCT) (n = 9) vs. 16.6 ± 0.7 (control) (n = 9) (P < 0.05); 29.1 ± 1.5 mmHg (CH) (n = 10) vs. 17.5 ± 0.5 (control) (n = 10) (P < 0.05)], RV/LV + S [0.40 ± 0.01 (MCT) (n = 18) vs. 0.24 ± 0.01 (control) (n = 10) (P < 0.05); 0.41 ± 0.03 (CH) (n = 13) vs. 0.27 ± 0.06 (control) (n = 10) (P < 0.05)], and %Muscularization and %MWT were increased by MCT injection and CH exposure. CLZ significantly attenuated these changes in the MCT model [mPAP 25.1 ± 1.1 mmHg (n = 11) (P < 0.05), RV/LV + S 0.30 ± 0.01 (n = 14) (P < 0.05)]. In contrast, these CLZ effects were not observed in the CH model. Lung eNOS protein expression was unchanged in the MCT model and increased in the CH model. Lung protein expression of AKT, phosphorylated AKT, and IκB was downregulated by MCT, which was attenuated by CLZ; the CH model did not change these proteins. Lung MCP-1 mRNA levels were increased in MCT rats but not CH rats. CONCLUSIONS: We found model differences in the effect of CLZ on PH development. CLZ might exert a preventive effect on PH development in an inflammatory PH model but not in a vascular structural change model of PH preceded by vasoconstriction. Thus, the preventive effect of CLZ on PH development might depend on the PH etiology.

Endfoot regeneration restricts radial glial state and prevents translocation into the outer subventricular zone in early mammalian brain development.

Neural stem cells, called radial glia, maintain epithelial structure during the early neocortical development. The prevailing view claims that when radial glia first proliferate, their symmetric divisions require strict spindle orientation; its perturbation causes precocious neurogenesis and apoptosis. Here, we show that despite this conventional view, radial glia at the proliferative stage undergo normal symmetric divisions by regenerating an apical endfoot even if it is lost by oblique divisions. We found that the Notch-R-Ras-integrin ß1 pathway promotes the regeneration of endfeet, whose leading edge bears ectopic adherens junctions and the Par-polarity complex. However, this regeneration ability gradually declines during the subsequent neurogenic stage and hence oblique divisions induce basal translocation of radial glia to form the outer subventricular zone, a hallmark of the development of the convoluted brain. Our study reveals that endfoot regeneration is a temporally changing cryptic property, which controls the radial glial state and its shift is essential for mammalian brain size expansion.