Effects of oral administration of nonselective Trk inhibitor on bladder overactivity in rodent models of prostatic inflammation.

BACKGROUND: Our research focused on the assessment of the impact of systemic inhibition of Trk receptors, which bind to nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), on bladder hypersensitivity in two distinct rodent models of prostatic inflammation (PI). METHODS: Male Sprague-Dawley rats were divided into three groups (n = 6 each): the control group (no PI, vehicle administration), the untreated group (PI, vehicle administration), and the treated group (PI, nonselective Trk inhibitor, GNF 5837, administration). PI in rats was induced by a intraprostatic injection of 5% formalin. Posttreatment, we carried out conscious cystometry and a range of histological and molecular analyses. Moreover, the study additionally evaluated the effects of a nonselective Trk inhibitor on bladder overactivity in a mouse model of PI, which was induced by prostate epithelium-specific conditional deletion of E-cadherin. RESULTS: The rat model of PI showed upregulations of NGF and BDNF in both bladder and prostate tissues in association with bladder overactivity and inflammation in the ventral lobes of the prostate. GNF 5837 treatment effectively mitigated these PI-induced changes, along with reductions in TrkA, TrkB, TrkC, and TRPV1 mRNA expressions in L6-S1 dorsal root ganglia. Also, in the mouse PI model, GNF 5837 treatment similarly improved bladder overactivity. CONCLUSIONS: The findings of our study suggest that Trk receptor inhibition, which reduced bladder hypersensitivity and inflammatory responses in the prostate, along with a decrease in overexpression of Trk and TRPV1 receptors in sensory pathways, could be an effective treatment strategy for male lower urinary tract symptoms associated with PI and bladder overactivity.

Perioperative Anaphylaxis in Japanese Secondary Care Institutions: Incidence, Causes, and the Imperative for Improved Diagnostic Practices.

Background This research investigates the incidence, suspected causes, and diagnostic procedures for perioperative anaphylaxis (POA), a potentially severe complication, in secondary care hospitals across Japan. Methodology We surveyed Saiseikai hospitals and gathered data on surgical procedures, POA occurrences, potential triggers, and diagnostic methods. Results Among 70,523 surgeries, seven were associated with POA, resulting in an approximate incidence rate of 0.01%. Rocuronium was the most commonly suspected trigger, followed by sugammadex, latex, and angiography contrast agents. Despite the importance of skin tests as the most basic and crucial diagnostic method, they were conducted in only three instances. No in vitro tests for drug identification were conducted, and in four cases, the cause was determined merely based on the timing of drug administration, indicating significant diagnostic limitations. Conclusions The study underscores the critical situation in Japan regarding insufficient diagnostic practices and difficulties in identifying triggering drugs rather than the consistent prevalence of POA in secondary care facilities. The findings emphasize the need for improved diagnostic proficiency and more rigorous drug identification practices to ensure prompt and accurate POA diagnosis. It is essential to conduct further research and interventions to increase patient safety during the perioperative period in secondary care settings.

Analysis of predictors of fever after aortic valve replacement: Diabetic patients are less likely to develop fever after aortic valve replacement, a single-centre retrospective study.

BACKGROUND: Postoperative temperature dysregulation affects the length of hospital stay and prognosis. This study evaluated the factors that influence the occurrence of fever in patients after aortic valve replacement surgery. METHODS: Eighty-seven consecutive patients who underwent aortic valve replacement surgery were included. Patients' age, sex and body mass index; presence of diabetes mellitus; operation time; blood loss; blood transfusion volume; preoperative and postoperative laboratory findings; presence or absence of oral function management; and fever >38°C were retrospectively analysed through univariate and multiple logistic regression analyses. RESULTS: Among the variables, only diabetes mellitus status was significantly associated with fever ⩾38°C. Postoperatively, patients with diabetes mellitus were significantly less likely to develop fever above 38°C and a fever rising to 38°C. CONCLUSIONS: This study shows that the presence of comorbid diabetes mellitus decreases the frequency of developing fever >38°C after aortic valve replacement surgery.

A Case of Consumptive Coagulopathy Before Cardiopulmonary Failure in Amniotic Fluid Embolism and Review of Literature: A Perspective of the Latent Onset and Progression of Coagulopathy.

Amniotic fluid embolism (AFE) induces cardiopulmonary insufficiency with consumptive coagulopathy. Previous studies reported that refractory coagulopathy has already advanced at the onset of maternal cardiovascular and/or respiratory symptoms. However, when the consumption of coagulation factors starts during the clinical course, AFE remains to be elucidated. We report an intrapartum AFE case of consumptive coagulopathy before dyspnea with hypotension developing during urgent cesarean delivery that was revealed by non-reassuring fetal heart rate tracing. The patient, a 42-year-old multiparous parturient, underwent induced labor after a premature rupture of membranes in week 39 of pregnancy. Coagulation screening was initially within the normal range. Fetal heart rate monitoring demonstrated bradycardia coincided with uterine tachysystole after three hours, which required urgent cesarean section with preoperative blood screening. The hemoglobin level was maintained at 129 g/L; however, the fibrinogen value reduced to 1.79 g/L with D-dimer elevation over 60 µg/mL. Ninety minutes later, she developed dyspnea with hypotension at suturing hysterotomy. At the end of surgery, her fibrinogen further decreased to below 0.3 g/L with prolonged prothrombin time. After vigorous intensive care, she was discharged without sequelae. Consumptive coagulopathy may initiate and progress before apparent cardiopulmonary symptoms in some AFE cases. Non-reassuring fetal heart rate tracing concomitant with abrupt uterine tachysystole and/or hypertonus may be an earlier time point for the detection and intervention of AFE-related coagulopathy.

Mirtazapine plus granisetron and dexamethasone for carboplatin-induced nausea and vomiting in patients with thoracic cancers: A prospective multicenter phase II trial.

BACKGROUND: Mirtazapine blocks 5-hydroxytryptamine type (5-HT)2A, 5-HT2C, 5-HT3 and histamine H1 receptors, similarly to olanzapine. This study aimed to investigate the efficacy and safety of mirtazapine plus granisetron and dexamethasone for carboplatin (CBDCA)-induced nausea and vomiting in patients with thoracic cancers. METHODS: We conducted a prospective, open-label, single-arm, multicenter, phase II trial in four institutions in Japan. Registered patients were moderately to highly emetogenic chemotherapy-naïve, and were scheduled to receive CBDCA at area under the curve (AUC) ≥ 4 mg/mL per minute. Patients received mirtazapine 15 mg/day orally at bedtime for four consecutive days, in combination with granisetron and dexamethasone. Primary endpoint was complete response (CR; no emesis and no use of rescue medication) rate during the delayed period (24-120 h). RESULTS: Between July 2022 and July 2023, 52 patients were enrolled, and 48 patients were evaluated. CR rates in the delayed (24-120 h), overall (0-120 h), and acute periods (0-24 h) were 83.3%, 83.3%, and 100%, respectively. No grade 3 or higher treatment-related adverse events were observed except for one patient who had grade 3 dry mouth as evaluated by Common Terminology Criteria for Adverse Events version 5.0. CONCLUSIONS: Prophylactic antiemetic therapy with mirtazapine plus granisetron and dexamethasone shows promising efficacy and an acceptable safety profile. This three-drug combination appears to be a reasonable treatment approach in patients with thoracic cancers receiving a CBDCA-based regimen at AUC ≥ 4 mg/mL per minute.

Association between an early revascularization strategy and major cardiac events based on left ventricular dyssynchrony in patients at intermediate risk of major cardiac events using the J-ACCESS risk model.

Objective This retrospective study aimed to investigate the association between therapeutic strategies and the development of major cardiac events (MCEs) in intermediate-risk patients by using the J-ACCESS risk model in combination with the stress phase bandwidth (SPBW), an index of left ventricular dyssynchrony. Methods Patients were followed-up for three years to confirm their prognosis. Based on the estimated propensity scores, the patients who underwent revascularization within the first 60 days after SPECT and those who did not were matched 1:1 (n = 367 per group). The composite endpoint was the occurrence of MCEs, consisting of cardiac death, non-fatal myocardial infarction, and severe heart failure. SPBW was calculated by a phase analysis using the Heart Risk View-F software program, and the MCE rate was compared between the two groups by applying the normal value of SPBW (38°). Patients The study included 2,053 patients with either known or suspected CAD who underwent electrocardiogram-gated single-photon emission computed tomography myocardial perfusion imaging and were at intermediate risk of MCE according to the J-ACCESS risk model. Results During follow-up, 54 of the 734 patients (7.4%) experienced MCEs. The overall incidence of MCE in intermediate-risk patients was not significantly different between the two groups. However, the incidence of MCE in patients with an abnormal SPBW was significantly lower in those who underwent early revascularization (4.8% vs. 11.9%, P = 0.0407). Conclusion The combination of the J-ACCESS risk model and the SPBW is thus considered to be an optimal treatment strategy for patients at intermediate risk of MCE, and early revascularization may lead to an improved prognosis in intermediate-risk patients with an abnormal SPBW.

Atypical Peripheral Retinal Necrosis Without Ocular Inflammation and Retinal Whitening in a Patient With Acute Myelogenous Leukemia: A Case Report.

Retinal necrosis is a severe condition that threatens visual function. It is caused by viruses that are known to cause acute retinal necrosis (ARN) and progressive outer retinal necrosis (PORN), which are called necrotizing herpetic retinopathies (NHR). ARN causes severe intraocular inflammation, including anterior chamber intravitreal cells, keratic precipitate, vitreous opacity, and retinal vasculitis, whereas intraocular inflammation in PORN is considered mild or virtually absent. In addition, PORN is a disease that manifests in immunosuppressive patients, such as those with acquired immunodeficiency syndrome. Here, we present a case of unilateral retinal necrosis after chemotherapy, allogeneic peripheral blood stem cell transplantation, and cord blood transplantation for acute myelogenous leukemia (AML) in a 31-year-old male patient. AML treatment resulted in metabolic remission, and oral steroids and tacrolimus were continued. After two days, the patient visited an ophthalmologist because he noticed a sudden onset of floaters and visual field disturbance in the left eye. The peripheral retina was already necrotic in all layers, causing total retinal detachment. Intraocular inflammation, retinal opacity, or hemorrhagic spots in the fundus were not observed. His previous CD4 count was 43 cells/µL. A polymerase chain reaction test of the anterior chamber fluid revealed varicella-zoster virus (VZV), and vitrectomy was performed four days after disease onset. The excised vitreous demonstrated minimal opacity. The peripheral necrotic retina was excised, photocoagulation was performed on the residual retinal limbus, and silicone oil was injected to maintain retinal attachment. The retinal restoration was maintained under silicone oil tamponade, and corrected visual acuity improved to 20/32 without strong inflammation after vitrectomy. However, two months postoperatively, he contracted coronavirus disease 2019 (COVID-19), his general condition rapidly deteriorated, and he died. This case of retinal necrosis without inflammatory results in an immunocompromised patient and VZV detection in an intraocular sample led us to suspect PORN. However, the patchy or spread retinal whitening characteristic of PORN was completely absent, whereas the well-defined, peripheral, full-layer retinal necrosis characteristic of ARN was present. Thus, this is a rare case of VZV-induced NHR with partial features of PORN and ARN that progressed very silently.

Surgically-Induced Necrotizing Scleritis After Scleral Buckling With Stenotrophomonas maltophilia Infection.

Surgically induced necrotizing scleritis (SINS) is a rare inflammatory disease of the sclera that occurs following ocular surgery, specifically pterygium surgery and scleral buckling. Here, we report a case of SINS in a 78-year-old female patient after segmental scleral buckling for rhegmatogenous retinal detachment. The retina was restored after scleral buckling, and the postoperative course was uneventful. However, the patient developed ocular discharge and conjunctival hyperemia, indicating infection, after two months. The sclera became thinner and intraocular inflammation developed after buckle removal. Stenotrophomonas maltophilia was isolated from the ocular discharge, and the patient was treated with antibacterial agents susceptible to the bacteria. However, her symptoms persisted, and corrected visual acuity decreased from 20/25 to 20/1000. Oral steroid treatment was initiated because of the suspicion of SINS. Intraocular inflammation gradually subsided, the thin sclera was covered by conjunctival tissue, and the patient's corrected visual acuity improved to 20/32, which stabilized her condition. Infection with Stenotrophomonas maltophilia after scleral buckling is extremely rare, and SINS development in such cases is unprecedented.

A randomized, double-blind, dose-controlled study of the use of dexmedetomidine alone for procedural sedation of children and adolescents undergoing MRI scans.

BACKGROUND: Dexmedetomidine is a selective α2-adrenergic agonist originally approved for sedation of adults in the intensive care unit and subsequently approved for procedural sedation in adults undergoing medical procedures. Dexmedetomidine is widely used off-label for procedural sedation in children. AIMS: To evaluate efficacy and safety of monotherapy dexmedetomidine for magnetic resonance imaging procedural sedation of children ≥1month-<17years across three ascending doses. METHODS: Randomized, double-blind, dose-ranging study of procedural sedation recruited patients at USA and Japanese sites from February 2020 to November 2021. Patients were stratified into Cohort A (≥1month-<2years) or Cohort B (≥2-<17years). Cohort A loading doses/maintenance infusions: 0.5 mcg/kg/0.5 mcg/kg/h, 1.0 mcg/kg/1.0 mcg/kg/h, and 1.5 mcg/kg/1.5 mcg/kg/h. Cohort B loading doses/maintenance infusions: 0.5 mcg/kg/0.5 mcg/kg/h, 1.2 mcg/kg/1.0 mcg/kg/h, and 2.0 mcg/kg/1.5 mcg/kg/h. Primary endpoint was percentage of overall patients completing MRI without rescue propofol at the high versus low dose. Key secondary endpoint was percentage in each age cohort who did not require propofol at the high versus low dose. RESULTS: One hundred twenty-two patients received high- (n = 38), middle- (n = 42), or low-dose (n = 42) dexmedetomidine. A greater percentage completed MRI without propofol rescue, while receiving high- versus low-dose dexmedetomidine (24/38 [63.2%] vs. 6/42 [14.3%]) (odds ratio: 10.29, 95% confidence interval: 3.47-30.50, p < .001). Similar results were seen in both age cohorts. The most common adverse events were bradypnea, bradycardia, hypertension, and hypotension, and the majority were of mild-to-moderate severity. CONCLUSIONS: Dexmedetomidine was well tolerated. The high dose was associated with meaningfully greater efficacy compared with lower doses. Based on these results, the recommended starting dose for procedural sedation in children ≥1month-<2years is loading dose 1.5 mcg/kg/maintenance infusion 1.5 mcg/kg/h; children ≥2-<17years is loading dose 2.0 mcg/kg/maintenance infusion 1.5 mcg/kg/h.

Triglyceride/high-density lipoprotein cholesterol ratio may be a better index of cardiometabolic risk in women than in men in Japan.

BACKGROUND AND AIMS: Few data exist regarding the gender differences in the relationship between triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and cardiometabolic risk leading to atherosclerotic cardiovascular disease (ASCVD). We investigated, by gender, the association between the TG/HDL-C ratio and metabolic syndrome (MetS) and its components in the Japanese, who are less obese than their Western counterparts. METHODS AND RESULTS: A population consisting of 10,373 participants (average age, 47.6 ± 12.6 years, 60.9 % men) at the Health Planning Center of Nihon University Hospital between April 2019 and March 2020 was studied using a cross-sectional study method. The TG/HDL-C ratio and proportion of visceral obesity increased approximately parallelly with age in women; however, these parameters did not change proportionally with age in men. Accordingly, receiver operating characteristic analysis revealed the accuracy of the TG/HDL-C ratio as a predictor of visceral obesity based on the Japanese MetS criteria (women vs. men: area under the curve, 0.797 vs. 0.712, p < 0.0001; sensitivity, 82.4 % vs. 59.9 %; specificity, 61.1 % vs. 71.1 %; cutoff value, 1.075 vs. 1.933, respectively). Furthermore, a higher TG/HDL-C ratio in women reflected the status of MetS and its components compared with men in multi-logistic regression analysis. CONCLUSION: An increased TG/HDL-C ratio in women may be involved in MetS and its components compared to men. We may pay attention to visceral obesity and increased TG/HDL-C ratio to prevent ASCVD risk in women, even in the Japanese population, which generally contains a lower proportion of obesity than in Western populations.

Detailed Protocol for Predicting 3D Structure of DNA Aptamers and Performing In Silico Docking Calculations.

This paper presents a comprehensive protocol for predicting the three-dimensional (3D) structure of DNA aptamers and performing in silico docking calculations. The protocol includes steps for sequence input, structure prediction, sequence modification, structure minimization, and docking. The procedure is executed on a Mac environment utilizing bioinformatics tools such as mfold, RNA Composer, PyMOL, and Hdock. The protocol is intended to provide a guide for researchers in structural biology and drug design.

Reconstruction of Protein/Liposome Complex.

Most ion channels and receptors are distributed in cell membranes and are known as membrane proteins. These membrane proteins are folded in the cell membrane and become functional proteins. Here, we demonstrate a method of reconstructing membrane proteins into liposome membranes, which are commonly used as artificial cell membranes.

Generation of Specific Aptamers.

Nucleic acid aptamers are therapeutic agents consisting of short single-strand DNA or RNA oligonucleotides, which have the ability to bind to target therapeutic molecules with high affinity and specificity and have been developed as potent drugs for the treatment of rheumatoid arthritis. Aptamers have unique and advantageous features over antibodies, such as superior affinity with nano- or pico-molar dissociation constants and ease of chemical synthesis, modification, and inactivation by designing antisense sequences. In this chapter, using a DNA-oligonucleotide pool, the technology of proteoliposome-systematic evolution of ligands by exponential enrichment (SELEX) is introduced. By using this technique, potential therapeutic agents with high affinity and specificity could be obtained.

Bulk RNA-seq Assessment of Murine Spleen Using a Portable MinION Sequencing Device.

Comprehensive profiling of the transcriptome reflects the dynamic changes in complex regulator interactions between genes and proteins in the pathological processes of autoimmune disease. To enable real-time adaptive sampling and run rapid sequencing with maximal expected readings of 50 Gb of data with accessibility to clinicians, basic researchers, and even students, a portable and affordable sequencing device, MinION, was employed in our laboratory for both basic and clinical studies. Here, the workflow of bulk RNA-seq in murine spleen using MinION is introduced. The methodology of both laboratory library preparation and the establishment of a bioinformatic pipeline are included in this chapter.

Dietary leucine supplementation restores T-cell mitochondrial respiration and regulates T-lineage differentiation in denervation-induced sarcopenic mice.

With the aim of offsetting immune dysfunction preceded by sarcopenia, the feasibility and efficiency of nutritional leucine supplementation were evaluated using a murine denervation-induced sarcopenia model. Sciatic nerve axotomy caused significant loss of skeletal muscle of the hind limbs and accelerated mitochondrial stress along with suppressed ATP production in spleen-derived T cells. Dietary leucine intake not only ameliorated muscle mass anabolism in a sarcopenic state, but also restored mitochondrial respiratory function, as indicated by elevated levels of basal respiration, maximal respiration, spare respiratory capacity, and ATP production, in T cells, which in turn led to downregulated expression of mTOR and downstream signals, as indicated by the findings of comprehensive transcriptome analysis. Consequentially, this finally resulted in amelioration of the sarcopenia-induced relative Th1/Th17-dominant proinflammatory microenvironment. These results highlight the importance of leucine-promoted metabolic cues in directing T cell fate in a sarcopenic microenvironment. The present study provides insights that particularly help rationalize the design and optimization of leucine supplementation for chronic sarcopenic patients with autoimmune diseases.

Criteria for immediate extubation after pediatric liver transplantation in a single pediatric liver transplant center in Japan.

Immediate extubation (IE) following liver transplantation (LT) has become the standard practice, even for pediatric patients. However, no preoperative or postoperative case selection protocols for IE are currently available. We have developed selection criteria for IE following pediatric LT. The aim of this study is to assess the safety and effectiveness of these selection criteria and anesthetic management protocol implemented in our hospital for IE after pediatric LT. METHOD: This was a retrospective study. The records of all cases undergoing LT in our center from January 2016 to December 2020 were collected. We excluded cases > 18 years old at the time of LT. Enrolled cases were divided into two groups: cases with immediate extubation (IE) or without immediate extubation (NIE). We compared preoperative conditions, intraoperative management, and postoperative courses. Finally, we classified NIE group patients into cases extubated at postoperative day 1 (early; E-NIE) and others (delayed; D-NIE) and compared their underlying diseases and postoperative courses. RESULTS: In the IE group, there were 81 cases, while the NIE group consisted of 185 cases. All patients in the IE group were successfully extubated without any instances of re-intubation due to respiratory failure. Within the E-NIE group, comprising 130 cases, all patients were ultimately extubated without the need for tracheostomy. However, in the D-NIE group, which encompassed 53 cases, seven patients required tracheostomy. CONCLUSION: In our center, the implementation of our anesthesia management protocol and the use of pre/postoperative case selection criteria have allowed for the safe practice of IE following pediatric LT. However, it should be noted that patients who cannot be extubated by Postoperative Day 1 (POD1) may be at an increased risk of requiring a tracheostomy. When contemplating IE, it is crucial to take into account the disease-specific physiological aspects and surgical site situations.

Impact of preoperative bloodstream infection on outcomes of pediatric liver transplant recipients treated for acute liver failure.

BACKGROUND: Acute liver failure (ALF) is a component of multisystem organ failure that causes severe liver dysfunction in patients without underlying chronic liver disease. The patients with ALF are prone to have infections, including bacteremia. However, studies of the infectious impact for post liver transplantation (LT) in pediatric ALF are limited. We aimed to evaluate our current practice for pediatric LT cases of ALF with preoperative bacteremia. METHODS: The records of all patients under 18 years old undergoing LT for ALF in our center from November 2005 to December 2021 were collected. They were divided into two groups: those with a preoperative bloodstream infection (BSI) and those without (NBSI). We compared the preoperative status and also reviewed the details of the BSI group. Intraoperative course and postoperative outcomes were also compared. RESULTS: There were 19 BSI patients and 66 NBSI patients. One BSI case was detected on the day of LT. This patient had no changes in vital signs and general condition. After evaluation and therapeutic intervention by pediatric infectious disease specialists, LT was performed on the same day. Five cases developed septic shock at the time of detection of BSI. All BSI patients were in stable condition on the operation day with proper interventions. There were no significant differences in mortality and hospital stay between both groups. CONCLUSIONS: LT might be able to be performed for pediatric ALF even with positive blood cultures. In addition, appropriate therapeutic intervention by specialists and patient's stable condition before LT are essential.

Association of Higher N-3 Polyunsaturated Fatty Acid Consumption and Aerobic Exercise with Lower Neutrophil-to-Lymphocyte Ratio: Implications of Anti-Atherosclerotic Effect of Fish Consumption.

INTRODUCTION: N-3 polyunsaturated fatty acids (n-3 PUFAs), abundant in oily fish, exert anti-inflammatory cardiovascular protective effects. We aimed to investigate the association between fish-derived n-3 PUFAs, lifestyle habits, and neutrophil-to-lymphocyte ratio (NLR), an atherosclerotic cardiovascular disease (ASCVD) marker. METHODS: This cross-sectional study included 6,950 participants with no history of ASCVD, who underwent annual health check-ups (average age, 46.3 ± 13.0 years; male:female ratio, 58.8%) between April 2019 and March 2020 at the Health Planning Center, Nihon University Hospital. We calculated n-3 PUFA consumption using a questionnaire and the Japan National Health and Nutrition Survey. RESULTS: The average fish consumption frequency and fish-derived n-3 PUFA consumption were 2.20 ± 1.28 days/week and 5.20 ± 3.11 g/week, respectively. A higher fish-derived n-3 PUFA consumption was associated with a lower NLR. Multiple-stepwise regression analysis revealed that higher fish-derived n-3 PUFA consumption and more aerobic exercise habits were significant independent determinants of lower NLR. Furthermore, higher fish-derived n-3 PUFA consumption was associated with habitual aerobic exercise habits. CONCLUSION: Thus, higher fish-derived n-3 PUFA consumption and more aerobic exercise habits may be synergistically associated with lower NLR. This association may explain the preventive effects of fish consumption on the ASCVD risk.

Anesthesia management in a child with mucopolysaccharidosis and toxic epidermal necrolysis: A case report.

Toxic epidermal necrolysis and mucopolysaccharidosis are both rare diseases that pose significant airway maintenance challenges to anesthesiologists. In this report, we describe the anesthesia management in a 4-year-old male with mucopolysaccharidosis type II who developed toxic epidermal necrolysis and presented for ophthalmic surgical procedures. Combined use of propofol and ketamine with the support of high-flow nasal oxygen enabled adequate analgesia and sedation while maintaining spontaneous ventilation and airway patency. The strategy presented in this report may contribute to enhancing the safety of sedation in spontaneously breathing children with abnormal airways.

Exploring an immortal Turritopsis sp. as a less conventional natural system for study of aging.

Aim: Given its excellent capability of escaping from unavoidable harm and death, Turritopsissp. (T. sp.) has captured the attention and fascination of scientists as a less conventional tool for aging research. The current study introduces a method for establishment of a research model and comprehensive transcriptomic analysis to reveal the structural and functional diversity of T. sp. Methods: T. sp. medusae collected from the Pacific Ocean near Japan were reared using a common laboratory setting. Tissues of the gastrovascular cavity part (GP) and nerve ring part (NP) were collected, and total RNA was extracted. Bulk RNA-seq was performed to compare the different transcriptome landscapes between GP and NP. Results: The GP fragment could be utilized for studies related to stress response and systemic senescence, while the NP fragment could be used to explore system rejuvenation, self-repair and regeneration. Conclusions: As a less conventional system for aging research, by employing the most recently developed tools and techniques in the genomic revolution, comprehensive elucidation of the composition, development, and functions of T. sp. enabled us to explore the underlying mechanisms of the response to environmental stress and rejuvenation.