Neonatal exposure to sevoflurane in mice causes deficits in maternal behavior later in adulthood.

BACKGROUND: In animal models, exposure to general anesthetics induces widespread increases in neuronal apoptosis in the developing brain. Subsequently, abnormalities in brain functioning are found in adulthood, long after the anesthetic exposure. These abnormalities include not only reduced learning abilities but also impaired social behaviors, suggesting pervasive deficits in brain functioning. But the underlying features of these deficits are still largely unknown. METHODS: Six-day-old C57BL/6 female mice were exposed to 3% sevoflurane for 6 h with or without hydrogen (1.3%) as part of the carrier gas mixture. At 7-9 weeks of age, they were mated with healthy males. The first day after parturition, the maternal behaviors of dams were evaluated. The survival rate of newborn pups was recorded for 6 days after birth. RESULTS: Female mice that received neonatal exposure to sevoflurane could mate normally and deliver healthy pups similar to controls. But these dams often left the pups scattered in the cage and nurtured them very little, so that about half of the pups died within a couple of days. Yet, these dams did not show any deficits in olfactory or exploratory behaviors. Notably, pups born to sevoflurane-treated dams were successfully fostered when nursed by control dams. Mice coadministered of hydrogen gas with sevoflurane did not exhibit the deficits of maternal behaviors. CONCLUSION: In an animal model, sevoflurane exposure in the developing brain caused serious impairment of maternal behaviors when fostering their pups, suggesting pervasive impairment of brain functions including innate behavior essential to species survival.

Coadministration of hydrogen gas as part of the carrier gas mixture suppresses neuronal apoptosis and subsequent behavioral deficits caused by neonatal exposure to sevoflurane in mice.

BACKGROUND: In animal models, several anesthetics induce widespread increases in neuronal apoptosis in the developing brain with subsequent neurologic deficits. Although the mechanisms are largely unknown, the neurotoxicity may, at least in part, be due to elevated oxidative stress caused by mitochondrial dysfunction. In an investigation of potential therapies that could protect against this type of damage, we studied the effects of molecular hydrogen on anesthetic-induced neurotoxicity in the developing mouse brain. METHODS: Six-day-old C57BL/6 mice were exposed to 3% sevoflurane for 6 h with or without hydrogen (< 1.3%) as part of the carrier gas mixture. Apoptosis was evaluated by immunohistochemical staining for cleaved caspase-3 (n = 8-10/group). Western blot analysis for cleaved poly-(adenosine diphosphate-ribose) polymerase was also performed to examine apoptosis (n = 3-6/group). Oxidative stress was assessed by immunohistochemical staining for 4-hydroxy-2-nonenal (n = 8/group). Long-term memory and social behavior were examined using the fear conditioning test and the sociability test, respectively (n = 18-20/group). RESULTS: Western blot analysis showed that coadministration of 1.3% hydrogen gas significantly (P < 0.001) reduced the level of neuronal apoptosis to approximately 40% compared with sevoflurane exposure alone. Immunohistochemical analysis showed that hydrogen reduced oxidative stress induced by neonatal sevoflurane exposure. Although neonatal sevoflurane exposure caused impairment in long-term memory and abnormal social behaviors in adulthood, mice coadministered hydrogen gas with sevoflurane did not exhibit these deficits. CONCLUSIONS: Inhalation of hydrogen gas robustly decreased neuronal apoptosis and subsequent cognitive impairments caused by neonatal exposure to sevoflurane.

Pulse wave transit time measurements of cardiac output in patients undergoing partial hepatectomy: a comparison of the esCCO system with thermodilution.

BACKGROUND: Measuring cardiac output accurately during anesthesia is thought to be helpful for safely controlling hemodynamics. Several minimally invasive methods to measure cardiac output have been developed as alternatives to thermodilution with pulmonary artery catheterization. We evaluated the reliability of a novel pulse wave transit time method of cardiac output assessment to trend with thermodilution cardiac output in patients undergoing partial hepatectomy. METHODS: Thirty-one patients (ASA physical status II or III) undergoing partial hepatectomy under general anesthesia were evaluated. Cardiac output measurements by pulse wave transit time method and by thermodilution were recorded after induction of anesthesia, after a change in body positioning to 20° head up, after a change to 20° head down, after volume challenge with 10 mL·kg hydroxyethyl starch 6%, during the Pringle maneuver, and immediately after Pringle maneuver release. Trending was assessed using Bland-Altman analysis and concordance analysis. RESULTS: The direction of change between consecutive pulse wave transit time measurements and the corresponding thermodilution measurements showed a concordance rate of 96.0% (lower 95% confidence interval = 64%), with limits of agreement -1.51 and 1.61 L·min. CONCLUSIONS: The pulse wave transit time method had good concordance but fairly wide limits of agreement with regard to trending in patients with changes in preload and systemic vascular resistance. There are potential inaccuracies when vasopressors are used to treat hypotension associated with decreased systemic vascular resistance. The study limitations are that the cardiac output data were collected in a nonblinded fashion, and an existing intraarterial catheter was used, although the system requires only routine, noninvasive cardiovascular monitors. This is a promising technique that currently has limitations and will require further improvements and clinical assessment.

Development of virtual reality content for learning Japan Prehospital Trauma Evaluation and Care initial assessment procedures.

Aim: The Japan Prehospital Trauma Evaluation and Care (JPTEC) is a standardized educational program for prehospital trauma care in Japan. The initial assessment in the JPTEC course comprises a training segment that includes a 30-min session. Given the limited face-to-face training due to the coronavirus disease 2019, virtual reality (VR) content has become an alternative. However, creating VR content typically requires the assistance of expert technicians. We aimed to create VR content for the initial assessment segment of the JPTEC and verify its educational effectiveness. Methods: We created VR content for learning the initial assessment of the JPTEC using our easy-to-use VR content creation system. The participants played the VR content for 15 min. The number of times they "cleared" (i.e., made a correct decision and completed the initial assessment) was recorded every 5 min. Then, a JPTEC-certified instructor tested their practical skills through face-to-face simulation. Results: The authors had no specialized skills and created the VR content in 2 days. Fourteen students used the material. They cleared the scenario 3 (3-4) times in the first 5 min in 15 min, 5 (4-5) times in the second 5 min, and 5 (5-5) times in the third 5 min (P < 0.05). All participants passed the practical evaluation. Conclusion: A shorter VR training developed using our easy-to-use VR content creation system can replace the 30-min JPTEC session on the initial assessment. This system allows for the free and easy creation of VR content.

Instructor Development Workshops for Advanced Life Support Training Courses Held in a Fully Virtual Space: Observational Study.

BACKGROUND: Various face-to-face training opportunities have been lost due to the COVID-19 pandemic. Instructor development workshops for advanced resuscitation (ie, advanced life support) training courses are no exception. Virtual reality (VR) is an attractive strategy for remote training. However, to our knowledge, there are no reports of resuscitation instructor training programs being held in a virtual space. OBJECTIVE: This study aimed to investigate the learning effects of an instructor development workshop that was conducted in a virtual space. METHODS: In this observational study, we created a virtual workshop space by using NEUTRANS (Synamon Inc)-a commercial VR collaboration service. The instructor development workshop for the advanced life support training course was held in a virtual space (ie, termed the VR course) as a certified workshop by the Japanese Association of Acute Medicine. We asked 13 instructor candidates (students) who participated in the VR course to provide a workshop report (VR group). Reports from a previously held face-to-face workshop (ie, the face-to-face course and group) were likewise prepared for comparison. A total of 5 certified instructor trainers viewed and scored the reports on a 5-point Likert scale. RESULTS: All students completed the VR course without any problems and received certificates of completion. The scores for the VR group and the face-to-face group did not differ at the level of statistical significance (median 3.8, IQR 3.8-4.0 and median 4.2, IQR 3.9-4.2, respectively; P=.41). CONCLUSIONS: We successfully conducted an instructor development workshop in a virtual space. The degree of learning in the virtual workshop was the same as that in the face-to-face workshop.

Neonatal desflurane exposure induces more robust neuroapoptosis than do isoflurane and sevoflurane and impairs working memory.

BACKGROUND: In animal models, neonatal exposure to volatile anesthetics induces neuroapoptosis, leading to memory deficits in adulthood. However, effects of neonatal exposure to desflurane are largely unknown. METHODS: Six-day-old C57BL/6 mice were exposed to equivalent doses of desflurane, sevoflurane, or isoflurane for 3 or 6 h. Minimum alveolar concentration was determined by the tail-clamp method as a function of anesthesia duration. Apoptosis was evaluated by immunohistochemical staining for activated caspase-3, and by TUNEL. Western blot analysis for cleaved poly-(adenosine diphosphate-ribose) polymerase was performed to examine apoptosis comparatively. The open-field, elevated plus-maze, Y-maze, and fear conditioning tests were performed to evaluate general activity, anxiety-related behavior, working memory, and long-term memory, respectively. RESULTS: Minimum alveolar concentrations at 1 h were determined to be 11.5% for desflurane, 3.8% for sevoflurane, and 2.7% for isoflurane in 6-day-old mice. Neonatal exposure to desflurane (8%) induced neuroapoptosis with an anatomic pattern similar to that of sevoflurane or isoflurane; however, desflurane induced significantly greater levels of neuroapoptosis than almost equivalent doses of sevoflurane (3%) or isoflurane (2%). In adulthood, mice treated with these anesthetics had impaired long-term memory, whereas no significant anomalies were detected in the open-field and the elevated plus-maze tests. Although performance in a working memory task was normal in mice exposed neonatally to sevoflurane or isoflurane, mice exposed to desflurane had significantly impaired working memory. CONCLUSIONS: In an animal model, neonatal desflurane exposure induced more neuroapoptosis than did sevoflurane or isoflurane and impaired working memory, suggesting that desflurane is more neurotoxic than sevoflurane or isoflurane.

Efficacy of Body Armor in Protection Against Blast Injuries Using a Swine Model in a Confined Space with a Blast Tube.

The purpose of this study was to clarify whether or not body armor would protect the body of a swine model using a blast tube built at National Defense Medical College, which is the first such blast tube in Japan. Seventeen pigs were divided into two groups: the body armor group and the non-body armor group. Under intravenous anesthesia, the pigs were tightly fixed in the left lateral position on a table and exposed from the back neck to the upper lumbar back to the blast wave and wind with or without body armor, with the driving pressure of the blast tube set to 3.0 MPa. When the surviving and dead pigs were compared, blood gas analyses revealed significant differences in PaO2, PaCO2, and pH in the super-early phase. All pigs injured by the blast wave and wind had lung hemorrhage. All 6 animals in the body armor group and 6 of the 11 animals in the control group survived for 3 hours after injury. Respiratory arrest immediately after exposure to the blast wave was considered to influence the mortality in our pig model. Body armor may have a beneficial effect in protecting against respiratory arrest immediately after an explosion.

[Central venous catheterization complication by a guide wire].

Central venous catheterization using the Seldinger technique is a well known and often used method. On the other hand, there are also well known complications by needle puncture or by indwelling catheter, there are few reports about a guide wire which got hung up around the tricuspid valve. We report a case in which a guide wire got hung up to the chordae tendineae of the tricuspid valve. To insert the AVA 3Xi (Edwards life science Co. Iervine) from the right internal jugular vein, we inserted a guide wire without ease. Resistance appeared when we tried to remove the wire for 20 cm from the inserted state. The X-ray and the transesophageal echocardiography, showed the guide wire in the right ventricle. As actions to be taken, we advanced the central vein catheter of the EXCV catheter kit (Nippon Sherwood Medical Industries Co., Ltd.) to the tip, and a the guide wire was easily removed. There are many reports of the complication by the central venepuncture, but there are few reports about the guide wire which was entrapped in the vicinity of a tricuspid valve. The tip of the guide wire in this case was bent excessively, but the cause of the damage did not become clear by investigation. When a guide wire became hard to withdraw, we should never withdraw a guide wire blindly, but should search a cause and we should use the material which was matched with the cause.

[Case of caesarean section using Cell Savers5+ in a patient with the placenta accreta associated with massive hemorrhage].

Placenta accreta which occurs as a complication of total placenta previa is comparatively rare. And the diagnosis of placenta accreta before the caesarean section (C-section) is difficult. We experienced an extremely difficult anesthesia management of placenta accrete because of critical hemorrhage during C-section. We used self-blood collection device Cell Saver5+ (Haemonetics Japan Ltd, Tokyo) for the massive bleeding of 25,500 ml. The Cell Saver could be used to treat life threatening bleeding in C-section without any side effects, although it is thought that the use of the self-blood collection device during C-section had the danger of the amniotic fluid embolism and fetal red cell ontamination. It is necessary to consider using the Cell Saver in the obstetrical operation for life-saving medical treatment in response to unexpected massive bleeding.

Molecular Hydrogen Prevents Social Deficits and Depression-Like Behaviors Induced by Low-Intensity Blast in Mice.

Detonation of explosive devices creates blast waves, which can injure brains even in the absence of external injuries. Among these, blast-induced mild traumatic brain injury (bmTBI) is increasing in military populations, such as in the wars in Afghanistan, Iraq, and Syria. Although the clinical presentation of bmTBI is not precisely defined, it is frequently associated with psycho-neurological deficits and usually manifests in the form of poly-trauma including psychiatric morbidity and cognitive disruption. Although the underlying mechanisms of bmTBI are largely unknown, some studies suggested that bmTBI is associated with blood-brain barrier disruption, oxidative stress, and edema in the brain. The present study investigated the effects of novel antioxidant, molecular hydrogen gas, on bmTBI using a laboratory-scale shock tube model in mice. Hydrogen gas has a strong prospect for clinical use due to easy preparation, low-cost, and no side effects. The administration of hydrogen gas significantly attenuated the behavioral deficits observed in our bmTBI model, suggesting that hydrogen application might be a strong therapeutic method for treatment of bmTBI.

Disaster Victim Identification: Psychological Distress and Posttraumatic Stress in Dentists After the 2011 Fukushima Disaster.

OBJECTIVE: To evaluate the correlates of psychological responses in dentists who conducted disaster victim identification (DVI) in Fukushima following the 2011 earthquake/tsunami/nuclear disaster. METHOD: Self-report questionnaires were administered to 49 male dentists six to nine months after the disaster. Psychological distress and posttraumatic stress were measured using the General Health Questionnaire-30 (GHQ-30) and Impact of Event Scale-Revised (IES-R), respectively. Independent variables included sociodemographic characteristics, participant disaster exposures, DVI-related exposures, and fear of radiation exposure during DVI. Hierarchical multiple regression analysis was performed to examine independent-dependent variable relations. RESULTS: Thirty-eight participants (77.6%) had examined ≥ 40 corpses, 20 (40.8%) reported ≥ 4 corpse-related exposures, and six (12.2%) reported ≥ 5 gruesome corpse exposures. Mean (SD) GHQ-30 and IES-R scores were 5.08 (5.31) and 9.90 (10.1), respectively. Higher levels of psychological distress were associated with younger age (adjusted ß = -0.29), extensive property loss (ß = 0.34), and anxiety for the future (ß = 0.33). Higher levels of posttraumatic stress were associated with extensive property loss (adjusted R2 = 17.7%, ß = 0.30). Neither outcome was associated with DVI-related exposures or fear of radiation exposure during DVI (p < 0.05). CONCLUSIONS: Dentists' psychological burden was associated with disaster, but not DVI, exposures.

Trial application of oxygen and carbon isotope analysis in tooth enamel for identification of past-war victims for discriminating between Japanese and US soldiers.

Stable isotope analysis has undergone rapid development in recent years and yielded significant results in the field of forensic sciences. In particular, carbon and oxygen isotopic ratios in tooth enamel obtained from human remains can provide useful information for the crosschecking of morphological and DNA analyses and facilitate rapid on-site prescreening for the identification of remains. This study analyzes carbon and oxygen isotopic ratios in the tooth enamel of Japanese people born between 1878 and 1930, in order to obtain data for methodological differentiation of Japanese and American remains from the Second World War. The carbon and oxygen isotopic ratios in the tooth enamel of the examined Japanese individuals are compared to previously reported data for American individuals (born post WWII), and statistical analysis is conducted using a discrimination method based on a logistic regression analysis. The discrimination between the Japanese and US populations, including Alaska and Hawaii, is found to be highly accurate. Thus, the present method has potential as a discrimination technique for both populations for use in the examination of mixed remains comprising Japanese and American fallen soldiers.

Mechanical allodynia but not thermal hyperalgesia is impaired in mice deficient for ERK2 in the central nervous system.

Extracellular signal-regulated kinase (ERK) plays critical roles in pain plasticity. However, the specific contribution of ERK2 isoforms to pain plasticity is not necessarily elucidated. Here we investigate the function of ERK2 in mouse pain models. We used the Cre-loxP system to cause a conditional, region-specific, genetic deletion of Erk2. To induce recombination in the central nervous system, Erk2-floxed mice were crossed with nestin promoter-driven cre transgenic mice. In the spinal cord of resultant Erk2 conditional knockout (CKO) mice, ERK2 expression was abrogated in neurons and astrocytes, but indistinguishable in microglia compared to controls. Although Erk2 CKO mice showed a normal baseline paw withdrawal threshold to mechanical stimuli, these mice had a reduced nociceptive response following a formalin injection to the hind paw. In a partial sciatic nerve ligation model, Erk2 CKO mice showed partially restored mechanical allodynia compared to control mice. Interestingly, thermal hyperalgesia was indistinguishable between Erk2 CKO and control mice in this model. In contrast to Erk2 CKO mice, mice with a targeted deletion of ERK1 did not exhibit prominent anomalies in these pain models. In Erk2 CKO mice, compensatory hyperphosphorylation of ERK1 was detected in the spinal cord. However, ERK1 did not appear to influence nociceptive processing because the additional inhibition of ERK1 phosphorylation using MEK (MAPK/ERK kinase) inhibitor SL327 did not produce additional changes in formalin-induced spontaneous behaviors in Erk2 CKO mice. Together, these results indicate that ERK2 plays a predominant and/or specific role in pain plasticity, while the contribution of ERK1 is limited.