Differential effects of remimazolam and propofol on heart rate variability during anesthesia induction.

PURPOSE: The effects of remimazolam on autonomic nervous activity have not been elucidated. We investigated the differential effects of remimazolam and propofol on autonomic nervous activity during anesthesia induction. METHODS: Thirty patients were randomly divided into a remimazolam group or a propofol group for anesthesia induction. Hemodynamics and indices of heart rate variability were recorded before and after anesthesia. Low frequency power (LF; 0.04-0.15 Hz, ms2) and high frequency power (HF; 0.15-0.4 Hz, ms2) were calculated from power spectral density of heart rate variability. LF reflects both sympathetic and parasympathetic activities and HF reflects parasympathetic activity. To investigate the balance between sympathetic and parasympathetic activities, the normalized unit (%) of LF (LF nu) and that of HF (HF nu) were calculated. Changes in LF nu (ΔLF nu) before and after anesthesia (ΔLF nu = LF nu at awake-LF nu after anesthesia) were compared between the groups. RESULTS: Remimazolam and propofol decreased blood pressure and power spectral density of heart rate variability. Remimazolam did not change LF nu and HF nu, while propofol increased LF nu and decreased HF nu (P = 0.020). ΔLF nu in the remimazolam group (1.4 ± 23.6%) were less than that in the propofol group (19.3 ± 22.4%, P = 0.0415). CONCLUSION: Remimazolam and propofol decreased autonomic nervous activity during anesthesia induction. Remimazolam preserved the balance of sympathetic and parasympathetic activities, while propofol modulated it to sympathetic dominance.

Aerosol boxes decrease aerosol exposure only in depressurized rooms during aerosol-generating procedures in a simulation study.

PURPOSE: The aim of this study was to compare aerosol exposure with or without an aerosol box in a pressurized/depressurized room during aerosol-generating procedures using an experimental model. METHODS: Cake flour (aerosol model) was expelled from an advanced life support training mannequin. The primary outcome measure was the number of 0.3-10 µm-sized particles at three locations corresponding to the physician, medical staff, and environmental aerosol exposure levels. The aerosol dispersion was visualized using a high-resolution video. The number of expelled particles was measured after artificial coughing during simulated tracheal intubation and extubation in four situations, with or without an aerosol box in a pressurized or depressurized room (≤ 2.5 Pa). RESULTS: The particles arising from tracheal intubation at the three positions in the four groups differed significantly in size (p < 0.05). The sizes of particles arising from extubation at the physicians' and medical staff's faces in the four groups differed significantly in size (p < 0.05). Post hoc analysis showed that the counts of all particles at the three positions were significantly lower in the depressurized room with an aerosol box than in the pressurized room without an aerosol box during tracheal intubation (p < 0.05 at three positions) and extubation (p < 0.05) at the physician's and medical staff's positions). Visual assessments supported these results. CONCLUSION: The aerosol box decreased the exposure of the aerosol to the physician, medical staff, and environment during aerosol-generating procedures in the depressurized room only.

Characterization of LILRB3 and LILRA6 allelic variants in the Japanese population.

Leukocyte immunoglobulin (Ig)-like receptors (LILRs) are encoded by members of a human multigene family, comprising 11 protein-coding genes and two pseudogenes. Among the LILRs, LILRB3 and LILRA6 show the highest homology with each other, along with high allelic and copy number variations. Therefore, it has been difficult to discriminate between them, both genetically and functionally, precluding disease association studies of LILRB3 and LILRA6. In this study, we carefully performed variant screening of LILRB3 and LILRA6 by cDNA cloning from Japanese individuals and identified four allelic lineages showing significantly high non-synonymous-to-synonymous ratios in pairwise comparisons. Furthermore, the extracellular domains of the LILRB3*JP6 and LILRA6*JP1 alleles were identical at the DNA level, suggesting that gene conversion-like events diversified LILRB3 and LILRA6. To determine the four allelic lineages from genomic DNA, we established a lineage typing method that accurately estimated the four allelic lineages in addition to specific common alleles from genomic DNA. Analysis of LILRA6 copy number variation revealed one, two, and three copies of LILRA6 in the Japanese-in-Tokyo (JPT) population. Flow cytometric analysis showed that an anti-LILRB3 antibody did not recognize the second most common lineage in the Japanese population, indicating significant amino acid differences across the allelic lineages. Taken together, our findings indicate that our lineage typing is useful for classifying the lineage-specific functions of LILRB3 and LILRA6, serving as the basis for disease association studies.

Tracer diffusion coefficients of Li+ ions in c-axis oriented LixCoO2 thin films measured by secondary ion mass spectrometry.

Lithium diffusion is a key factor in determining the charge/discharge rate of Li-ion batteries. Herein, we study the tracer diffusion coefficient (D*) of lithium ions in the c-axis oriented LiCoO2 thin film using secondary ion mass spectrometry (SIMS). We applied a step-isotope-exchange method to determine D* in the Li-extracted LixCoO2. The observed values of D* ranged from 2 × 10-12 to 3 × 10-17 cm2 s-1 depending on the compositions in the range of 0.4 < x < 1.0. Approaching the stoichiometric composition (x = 1.0), D* decreases steeply to the minimum, which can be explained by the vacancy diffusion mechanism. Electrochemically determined diffusion coefficients corrected by thermodynamic factors are found to be in good agreement with D* determined by our method, over a wide range of compositions. The c-axis diffusion was explained by the migration of Li+ ions from one layer to another through additional diffusion channels, such as antiphase boundaries and a pair of Li antisite and oxygen vacancies in cobalt oxide layers.

Identification of the hybrid gene LILRB5-3 by long-read sequencing and implication of its novel signaling function.

Leukocyte immunoglobulin (Ig)-like receptors (LILRs) on human chromosome 19q13.4 encode 11 immunoglobulin superfamily receptors, exhibiting genetic diversity within and between human populations. Among the LILR genes, the genomic region surrounding LILRB3 and LILRA6 has yet to be fully characterized due to their significant sequence homology, which makes it difficult to differentiate between them. To examine the LILRB3 and LILRA6 genomic region, a tool named JoGo-LILR CN Caller, which can call copy number from short-read whole genome sequencing (srWGS) data, was applied to an extensive international srWGS dataset comprising 2,504 samples. During this process, a previously unreported loss of both LILRB3 and LILRA6 was detected in three samples. Using long-read sequencing of these samples, we have discovered a novel large deletion (33,692 bp) in the LILRB3 and LILRA6 genomic regions in the Japanese population. This deletion spanned three genes, LILRB3, LILRA6, and LILRB5, resulting in LILRB3 exons 12-13 being located immediately downstream of LILRB5 exons 1-12 with the loss of LILRA6, suggesting the potential expression of a hybrid gene between LILRB5 and LILRB3 (LILRB5-3). Transcription and subsequent translation of the LILRB5-3 hybrid gene were also verified. The hybrid junction was located within the intracellular domain, resulting in an LILRB5 extracellular domain fused to a partial LILRB3 intracellular domain with three immunoreceptor tyrosine-based inhibitory motifs (ITIMs), suggesting that LILRB5-3 acquired a novel signaling function. Further application of the JoGo-LILR tool to srWGS samples suggested the presence of the LILRB5-3 hybrid gene in the CEU population. Our findings provide insight into the genetic and functional diversity of the LILR family.

Investigations into the efficacy of a novel extubation-aerosol shield: a cough model study.

BACKGROUND: Physicians have had to perform numerous extubation procedures during the prolonged coronavirus disease 2019 (COVID 19) pandemic. Future pandemics caused by unknown pathogen may also present a risk of exposure to infectious droplets and aerosols. AIM: This study evaluated the ability of a newly developed aerosol barrier, "Extubation-Aerosol (EA)-Shield" to provide maximum protection from aerosol exposure during extubation via an aerosolised particle count and high-quality visualisation assessments. METHODS: We employed a cough model having parameters similar to humans and used micron oil aerosol as well as titanium dioxide as aerosol tracers. Aerosol barrier techniques employing a face mask (group M) and EA-Shield (group H) were compared. FINDINGS: The primary outcome was the difference in the number of particles contacting the physician's face before and after extubation. The maximum distances of aerosol dispersal after extubation were measured as the secondary outcomes. All aerosolised particles of the two tracers were significantly smaller in group H than in group M (p < 0.05). In addition, the sagittal and axial maximum distances and sagittal areas of aerosol dispersal for 3, 5, and 10 s after extubation were significantly smaller in group H than in group M (p < 0.05). CONCLUSION: This model indicates that EA-Shield could be highly effective in reducing aerosol exposure during extubation. Therefore, we recommend using it as an aerosol barrier when an infectious aerosol risk is suspected.

Differential regulation of gonadotropin-releasing hormone by corticotropin-releasing factor family peptides in hypothalamic N39 cells.

Corticotropin-releasing factor (CRF) is involved in a variety of physiological functions including regulation of hypothalamo-pituitary-adrenal axis activity during stressful periods. Urocortins (Ucns) are known to be members of the CRF family peptides. CRF has a high affinity for CRF receptor type 1 (CRF(1) receptor). Both Ucn2 and Ucn3 have very high affinity for CRF receptor type 2 (CRF(2) receptor) with little or no binding affinity for the CRF(1) receptor. Gonadotropin-releasing hormone (GnRH) is known to be involved in the regulation of the stress response. Gonadotropin-inhibitory hormone (GnIH) neurons interact directly with GnRH neurons, and the action of GnIH is mediated by a novel G-protein coupled receptor, Gpr147. This study aimed to explore the possible function of CRF family peptides and the regulation of GnRH mRNA in hypothalamic GnRH cells. Both mRNA and protein expression of the CRF(1) receptor and CRF(2) receptor were found in hypothalamic GnRH N39 cells. CRF suppressed GnRH mRNA levels via the CRF(1) receptor, while Ucn2 increased the levels via the CRF(2) receptor. Both CRF and Ucn2 increased Gpr147 mRNA levels. The results indicate that CRF and Ucn2 can modulate GnRH mRNA levels via each specific CRF receptor subtype. Finally, CRF suppressed GnRH protein levels, while Ucn2 increased the levels. Differential regulation of GnRH by CRF family peptides may contribute to the stress response and homeostasis in GnRH cells.

Reevaluation of solubility of tolbutamide and polymorphic transformation from Form I to unknown crystal form.

Thermodynamic stability order of tolbutamide between polymorphs was evaluated using calorimetry and spectroscopic analysis. The heat of solution (DeltaH) of Forms I-III measurements were carried out in dimethylsulfoxide between 298.2K and 319.2K. It was found that the DeltaH of Forms II and III was increased nearly parallel with a temperature rise. However, change of the DeltaH of Form I with a temperature rise was not in correspondence with that of other forms. Solubility data confirmed the change in DeltaH of Form I around 308.2K. XRD-DSC measurement of Form I detected a polymorphic transformation (Form I(L)-->unknown form) at 311K. Obtained data suggested that the new crystal form (Form I(H)) would exist above 311K, and the order of thermodynamic stability was "Form III