Effectiveness of Body Armor Against Shock Waves: Preventing Blast Injury in a Confined Space.

Introduction Blast injuries in modern society often occur owing to terrorist attacks in confined spaces, particularly in urban settings, indoors, and in vehicles, leading to significant damage. Therefore, it is important to focus on blast injuries in confined spaces rather than in conventional open-field experiments. Materials and methods We used an air-driven shock wave generator (blast tube) established indoors in 2017 and conducted basic research to potentially save the lives of patients with blast injuries. Under general anesthesia, pigs were divided into with body armor (BA) and without BA groups. The pigs were fixed in the measurement chamber with their dorsal chest directly exposed to the shock wave. The driving pressure was set at 3.0 MPa to achieve a mortality rate of approximately 50%. A generated shock wave was directly applied to the pigs. Comparisons were made between the groups with respect to cardiac arrest and survival, as well as apnea, bradycardia, and hypotension, which are the triad of blast lung. Autopsies were performed to confirm the extent of the organ damage. Statistical analysis was performed using Fisher's exact test, and statistical significance was set at p<0.05. The animal experimentation was conducted according to the protocol reviewed and approved by the Animal Ethics Committee of the National Defense Medical College Hospital (approval number 19041). Results Eight pigs were assigned to the BA group and seven pigs to the non-BA group. In the non-BA group, apnea was observed in four of seven cases, three of which resulted in death. None of the eight pigs in the BA group had respiratory arrest; notably, all survived. Hypotension was observed in some pigs in each group; however, there were no cases of bradycardia in either group. Statistical analysis showed that wearing BA significantly reduced the occurrence of respiratory and cardiac arrest (p=0.026) but not survival (p=0.077). No significant differences were found in other vital signs. Conclusions Wearing BA with adequate neck and chest protection reduced mortality and it was effective to reduce cardiac and respiratory arrest against shock wave exposure. Mortality from shock wave injury appears to be associated with respiratory arrest, and the avoidance of respiratory arrest may lead to survival.

BK channel dysfunction disrupts attention-controlled behaviors and altered perseverative responses in murine instrumental learning.

This study examined the effect of knockout of KCNMA1 gene, coding for the BK channel, on cognitive and attentional functions in mice, with an aim to better understand its implications for human neurodevelopmental disorders. The study used the 3-choice serial reaction time task (3-CSRTT) to assess the learning performance, attentional abilities, and repetitive behaviors in mice lacking the KCNMA1 gene (KCNMA1-/-) compared to wild-type (WT) controls. Results showed no significant differences in learning accuracy between the two groups. However, KCNMA1-/- mice were more prone to omitting responses to stimuli. In addition, when the timing of cue presentation was randomized, the KCNMA1-/- showed premature responses. Notably, these mice also demonstrated a marked reduction in perseverative responses, which include repeated nose-poke behaviors following decisions. These findings highlight the involvement of the KCNMA1 gene in managing attention, impulsivity, and potentially moderating repetitive actions.

Real-time fetal monitoring using photoacoustic measurement of placental oxygen saturation in a rabbit hypoxia model.

INTRODUCTION: Ensuring adequate fetal oxygenation is an essential aim of fetal monitoring. The purpose of this study was to establish a basic technique for real-time measurement of blood oxygen saturation of the placenta by photoacoustic (PA) technique as a new fetal monitoring method. METHODS: The hypoxia model established in our previous study was applied to 7 pregnant rabbits. Three phases were induced: normal phase, hypoxia phase, and recovery phase. Three methods were simultaneously used for real-time fetal monitoring: fetal heat rate (FHR) monitoring, oxygen saturation (SO2) measurement by near-infrared spectroscopy (SNO2), and placenta SO2 measured by PA technique (SplO2). The maternal hypoxia was assessed by skin SO2 measured by PA technique (SsO2), and arterial blood SO2 by blood gas analysis (SaO2). RESULTS: The average of SplO2 in normal phase was 52.6 ± 13.9 %. The averages of SNO2, SSO2, and SplO2 in the seven rabbits changed in parallel from the normal phase to hypoxia phase. In the recovery phase, the SplO2 rose in parallel with recovery of SaO2. There was lag in increase of the FHR compared to the change in the other values. In the detailed analysis of PA signals from the labyrinth and decidua, a unique change in oxygen saturation was seen in one case. DISCUSSION: Results of this study showed that sensitivity of our novel PA technique in detecting tissue hypoxia was similar to near-infrared spectroscopy (NIRS). As an advantage, unlike NIRS, monitoring with PA technique was unaffected by ischemia and surface changes in oxygen saturation because of its higher spatial resolution. We conclude that PA technique provides more accurate information about fetal blood placenta than NIRS. Ultrasound imaging, combined with oxygen saturation monitoring by PA technique, would improve fetal monitoring and fetal diagnosis in the future.

HDL Functions-Current Status and Future Perspectives.

Cardiovascular disease (CVD) is the leading cause of death in Western countries. A low HDL-C is associated with the development of CVD. However, recent epidemiology studies have shown U-shaped curves between HDL-C and CVD mortality, with paradoxically increased CVD mortality in patients with extremely high HDL-C levels. Furthermore, HDL-C raising therapy using nicotinic acids or CETP inhibitors mostly failed to reduce CVD events. Based on this background, HDL functions rather than HDL-C could be a novel biomarker; research on the clinical utility of HDL functionality is ongoing. In this review, we summarize the current status of HDL functions and their future perspectives from the findings of basic research and clinical trials.

Medical Problems and Concerns with Temporary Evacuation Shelters after Great Earthquake Disasters in Japan: A Systematic Review.

Japan has repeatedly suffered from natural disasters. A number of temporary evacuation shelters have been opened for the benefit of evacuees. Although the operation of such evacuation shelters has improved after the Great Hanshin-Awaji Earthquake (1995), a number of operational difficulties were encountered during the Great East Japan Earthquake in 2011 and the Kumamoto Earthquake in 2016. A systematic literature review was conducted to identify the medical concerns encountered in temporary evacuation shelters by focusing on unsanitary environment, food and nutrition, and shortage of medication. Actual sanitary conditions have been found to be below the standards stipulated by the Japanese government as per international guidelines. Food aid in evacuation shelters was neither nutritionally balanced, nor was the distribution to different shelters balanced. Furthermore, evacuees with chronic diseases feared that there may be a shortage of medication. Crowding in evacuation shelters increased the risk of outbreaks of infectious diseases (e.g., tuberculosis). Malnutrition and shortage of medication exacerbated the risk of deterioration of chronic diseases (e.g., diabetes mellitus, hypertension) among evacuees. Therefore, it is recommended that healthcare professionals should be promptly deployed to evacuation shelters, to promote sanitary control and education, as well as address limited space availability, and food and medication shortage.

Photodynamic Inactivation of an Endodontic Bacteria Using Diode Laser and Indocyanine Green-Loaded Nanosphere.

Apical periodontitis, an inflammatory lesion causing bone resorption around the apex of teeth, is treated by eradicating infectious bacteria from the root canal. However, it has a high recurrence rate and often requires retreatment. We investigated the bactericidal effect of antimicrobial photodynamic therapy (aPDT)/photodynamic antimicrobial chemotherapy (PACT) using indocyanine green (ICG)-loaded nanospheres coated with chitosan and a diode laser on a biofilm of Enterococcus faecalis, a pathogen of refractory apical periodontitis. Biofilm of E. faecalis was cultured in a porcine infected root canal model. ICG solution was injected into the root canal, which was then irradiated with a laser (810 nm wavelength) from outside the root canal. The bactericidal effect was evaluated by colony counts and scanning electron microscopy. The result of the colony counts showed a maximum 1.89 log reduction after irradiation at 2.1 W for 5 min. The temperature rise during aPDT/PACT was confirmed to be within a safe range. Furthermore, the light energy transmittance through the root was at a peak approximately 1 min after the start of irradiation, indicating that most of the ICG in the root canal was consumed. This study shows that aPDT/PACT can suppress E. faecalis in infected root canals with high efficiency.

Neural extracellular vesicle-derived miR-17 in blood as a potential biomarker of subthreshold depression.

Subthreshold depression (StD) is a depressive state that does not fulfil the criteria for major depressive disorder (MDD); however, StD has a risk for progression to MDD, and early intervention is therefore needed. Recently, a method for extracting neural extracellular vesicles (NEVs) excreted from neural cells of the brain from blood has been established, and microRNAs (miRNAs) encapsulated in NEVs are attracting interest because of their potential correlation to the pathogenesis of psychiatric disorders. However, miRNAs closely related to StD are still unknown. Therefore, to try to identify miRNAs closely related to the degree of StD, we examined the correlations between expression levels of some candidate miRNAs in NEVs and Patient Health Questionnaire-9 (PHQ-9) scores in subjects. Total RNAs in NEVs were extracted from serum of young adult males who had PHQ-9 scores of less than 10 (n = 9). Expression levels of eight miRNAs that were previously reported to be depression-associated miRNAs (let-7a-5p, miR-17-5p, miR-26b-5p, miR-34a-5p, miR-132-3p, miR-182-5p, miR-212-3p, and miR-1202) were measured using real-time PCR. Two of the eight miRNAs (miR-17-5p and miR-26b-5p) were stably detected. The relative expression levels of miR-17-5p showed a significant positive correlation with PHQ-9 scores (r = 0.85, p < 0.01), while those of miR-26b-5p showed no significance. Although a larger-scale analysis is needed due to the small number of subjects, these findings suggest that miR-17-5p in NEVs is a potential biomarker for StD.

Deletion of Superoxide Dismutase 1 Blunted Inflammatory Aortic Remodeling in Hypertensive Mice under Angiotensin II Infusion.

Superoxide dismutase (SOD) is an enzyme that catalyzes the dismutation of two superoxide anions (O2·-) into hydrogen peroxide (H2O2) and oxygen (O2) and is generally known to protect against oxidative stress. Angiotensin II (AngII) causes vascular hypertrophic remodeling which is associated with H2O2 generation. The aim of this study is to investigate the role of cytosolic SOD (SOD1) in AngII-induced vascular hypertrophy. We employed C57/BL6 mice (WT) and SOD1 deficient mice (SOD1-/-) with the same background. They received a continuous infusion of saline or AngII (3.2 mg/kg/day) for seven days. The blood pressures were equally elevated at 1.5 times with AngII, however, vascular hypertrophy was blunted in SOD1-/- mice compared to WT mice (WT mice 91.9 ± 1.13 µm versus SOD1-/- mice 68.4 ± 1.41 µm p < 0.001). The elevation of aortic interleukin 6 (IL-6) and phosphorylation of pro-inflammatory STAT3 due to AngII were also blunted in SOD1-/- mice's aortas. In cultured rat vascular smooth muscle cells (VSMCs), reducing expression of SOD1 with siRNA decreased AngII induced IL-6 release as well as phosphorylation of STAT3. Pre-incubation with polyethylene glycol (PEG)-catalase also attenuated phosphorylation of STAT3 due to AngII. These results indicate that SOD1 in VSMCs plays a role in vascular hypertrophy due to increased inflammation caused by AngII, probably via the production of cytosolic H2O2.

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.

Nylon mesh-based 3D scaffolds for the adherent culture of neural stem/progenitor cells.

We developed novel scaffolds for the adherent culture of neural stem/progenitor cells on the woven mesh. Nylon mesh (NM) is an inert material for cell adhesion. We prepared polyacrylic acid-grafted nylon mesh (PAA-NM) by graft polymerization method using gamma-irradiation. Matrigel was covalently immobilized to the carboxyl groups in PAA-NM by chemical conjugation using 1-ethyl-3-(3-dimethylamino propyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) to prepare the Matrigel-immobilized PAA-grafted nylon mesh (M-PAA-NM). Cell adhesion property of mouse neural stem/progenitor cells (NSPCs) between the NM, PAA-NM, and M-PAA-NM was different from each other. The neurosphere-like clusters of NSPCs were weakly bound to NM and PAA-NM without spreading. The NSPCs were firmly adhered to, spread, and covered the surface of M-PAA-NM. We evaluated the state of differentiation by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immnocytochemistry. A neuronal marker ß III tubulin, a glial marker glial fibrillary acidic protein (GFAP) and a mature glial marker S100ß were expressed at a low level in the cultured cells while immature NSPCs marker Nestin and Sox2 were slightly lower without significant statistical difference. We concluded that the M-PAA-NM is a good substrate for adherent culture of NSPCs without triggering their cell differentiation, and also provides the maintenance of their growth with fewer passages in comparison with the conventional suspension culture of NSPCs in neurospheres.

Skin Cleansing Technique with Disinfectant using Improved High-Velocity Steam-Air Micromist Jet Spray.

Application of a high-velocity steam-air micromist jet spray (HVS-AMJS) with disinfectants for cleansing the skin is proposed. Low-pressure steam is mixed with compressed air in a nozzle and then sprayed onto a surface of skin or material located approximately 22 cm from the nozzle. The temperature on the sprayed surface was controlled between 40ºC and 45 ºC. The improved HVS-AMJS installed scattering prevention cover with tap water effectively removed normal bacterial flora (total viable count and coliform bacteria) from contaminated skin pieces and pig skin wounds. Furthermore, the cleansing efficacy increased by advanced-treating with bio-shell calcium oxide (BiSCaO), hypochlorous acid (HClO), sodium hypochlorite (NaClO), povidone iodine, or chlorhexidine gluconate. Especially, the improved HVS-AMJS combined with BiSCaO had higher bactericidal activity than when combined with other disinfectants. This study suggests that application of the HVS-AMJS with disinfectants, especially BiSCaO, may be useful for skin cleansing to prevent infection.

Heparinoid Complex-Based Heparin-Binding Cytokines and Cell Delivery Carriers.

Heparinoid is the generic term that is used for heparin, heparan sulfate (HS), and heparin-like molecules of animal or plant origin and synthetic derivatives of sulfated polysaccharides. Various biological activities of heparin/HS are attributed to their specific interaction and regulation with various heparin-binding cytokines, antithrombin (AT), and extracellular matrix (ECM) biomolecules. Specific domains with distinct saccharide sequences in heparin/HS mediate these interactions are mediated and require different highly sulfated saccharide sequences with different combinations of sulfated groups. Multivalent and cluster effects of the specific sulfated sequences in heparinoids are also important factors that control their interactions and biological activities. This review provides an overview of heparinoid-based biomaterials that offer novel means of engineering of various heparin-binding cytokine-delivery systems for biomedical applications and it focuses on our original studies on non-anticoagulant heparin-carrying polystyrene (NAC-HCPS) and polyelectrolyte complex-nano/microparticles (N/MPs), in addition to heparin-coating devices.

New endovascular perforation subarachnoid hemorrhage model for investigating the mechanisms of delayed brain injury.

OBJECTIVE: Delayed brain injury (DBI) is considered one of the most important causes of mortality and morbidity after subarachnoid hemorrhage (SAH). However, no suitable experimental rat endovascular perforation (EVP) SAH model was available for investigating DBI. The authors added early cerebral hypoperfusion to a mild EVP SAH model by unilateral common carotid artery occlusion (UCCAO) 24 hours after induction of SAH to mimic the clinical course of early cerebral hypoperfusion after SAH. METHODS: A total of 109 adult male Sprague-Dawley rats were randomly divided into 2 groups: no SAH and SAH. Next, no-SAH rats were randomly divided on day 1 into 2 groups: sham and UCCAO. SAH rats with a neurological score of 15 or greater were randomly divided into 2 groups: SAH - UCCAO and SAH + UCCAO group. RESULTS: The mild SAH model had a lower mortality rate of 5.4% within the first 24 hours. No rat died in the SAH + UCCAO group until day 7. DBI as well as early brain injury (EBI), reactive astrogliosis, and cerebral vasospasm significantly worsened in the SAH + UCCAO group. CONCLUSIONS: The present SAH + UCCAO model can simulate EBI with aggravation of reactive astrogliosis, cerebral vasospasm, and DBI but without high mortality.

Preparation and Application of Bioshell Calcium Oxide (BiSCaO) Nanoparticle-Dispersions with Bactericidal Activity.

Scallop-shell powder (SSP) heated at high temperature exhibits high pH and broad antimicrobial activity. Bioshell calcium oxide (BiSCaO) is an SSP composed mainly of calcium oxide. It is poorly water-soluble under alkaline conditions and the generated precipitate can plug spray nozzles. The aim of this study was to establish that BiSCaO dispersion caused no significant CaO loss and plugging of spray nozzles, and to evaluate its deodorization and microbicidal abilities and its ability to reduce the concentrations of NO2- and NO3-. BiSCaO dispersions were prepared by mixing various concentrations of BiSCaO suspension, while phosphate compounds such as Na3PO4, Na2HPO4 or NaH2PO4 and the pH, average diameter, zeta potential, and form of the compounds with cryo-SEM were evaluated. We evaluated deodorization using tainted pork meat and microbicidal efficacy using contaminated suspension with normal bacterial flora. The concentration of NO2- and NO3- after mixing BiSCaO dispersion and pure water containing a high proportion of NO2- and NO3- were measured. BiSCaO dispersion formed with Na2HPO4, whose ratio to BiSCaO was 60%, showed a high pH (>12), a small particle diameter (>181 nm) and was stable for seven days. The BiSCaO dispersion showed higher deodorization and microbicidal activities than SSP-Ca(OH)2, which was mainly composed of Ca(OH)2. BiSCaO, but not SSP-Ca(OH)2, could reduce the concentration of NO2- and NO3- by more than 90% within 15 min. We developed a stable BiSCaO dispersion, and it had high deodorization and microbicidal efficacy. These activities of BiSCaO might result from the high pH caused by CaO hydration and a reduction activity causing active radical species.

Profiling of the antibody response to attenuated LC16m8 smallpox vaccine using protein array analysis.

Concerns about bioterrorism and outbreaks of zoonotic orthopoxvirus require safe and efficacious smallpox vaccines. We previously reported the clinical efficacy and safety profiles of LC16m8, a live, attenuated, cell culture-derived, smallpox vaccine, examined in over 3000 healthy Japanese adults with various vaccination histories. In this study, serum of approximately 200 subjects pre and post LC16m8 vaccination were subjected to a vaccinia virus-specific protein array to evaluate the proteome-wide immunogenicity. The relationships between antigen-specific antibodies and plaque reduction neutralization titers were analyzed. LC16m8 induced antibodies to multiple vaccinia antigens in primary-vaccinated individuals and yielded effective booster responses in previously vaccinated individuals, demonstrating similar antibody profiles to those reported for other vaccinia virus strains. Several immunodominant antigens were indicated to be important for neutralization of the intracellular mature virion. The similarity of antibody profiles between LC16m8 and other smallpox vaccine strains supports the immunogenicity and protective efficacy of LC16m8.

Synthesis and Application of Silver Nanoparticles (Ag NPs) for the Prevention of Infection in Healthcare Workers.

Silver is easily available and is known to have microbicidal effect; moreover, it does not impose any adverse effects on the human body. The microbicidal effect is mainly due to silver ions, which have a wide antibacterial spectrum. Furthermore, the development of multidrug-resistant bacteria, as in the case of antibiotics, is less likely. Silver ions bind to halide ions, such as chloride, and precipitate; therefore, when used directly, their microbicidal activity is shortened. To overcome this issue, silver nanoparticles (Ag NPs) have been recently synthesized and frequently used as microbicidal agents that release silver ions from particle surface. Depending on the specific surface area of the nanoparticles, silver ions are released with high efficiency. In addition to their bactericidal activity, small Ag NPs (<10 nm in diameter) affect viruses although the microbicidal effect of silver mass is weak. Because of their characteristics, Ag NPs are useful countermeasures against infectious diseases, which constitute a major issue in the medical field. Thus, medical tools coated with Ag NPs are being developed. This review outlines the synthesis and utilization of Ag NPs in the medical field, focusing on environment-friendly synthesis and the suppression of infections in healthcare workers (HCWs).

Comparison of Various Disinfectants on Bactericidal Activity Under Organic Matter Contaminated Environments.

The bactericidal activity of heated bio-shell calcium oxide (BiSCaO) powder suspension (pH 12.4) , hypochlorous acid (HClO; pH 6), sodium hypochlorite (NaClO; pH 8) , povidone-iodine (Isodine solution®) , and chlorhexidine gluconate (Hibiscrub®) under organic matter contaminated environments were compared for tests conducted on wood scraps and pig skin pieces that were incubated with normal bacterial flora (total viable counts and coliform bacteria) . The test results showed that BiSCaO suspension had higher bactericidal activity than HClO and NaClO. Furthermore, more than 10-fold higher concentrations of antiseptics such as povidone-iodine and chlorhexidine gluconate were required to achieve bactericidal activity comparable to that of BiSCaO suspension. Our results demonstrate the possibility of using BiSCaO suspension under organic matter contaminated environments as a disinfectant for environmental and food hygiene applications.

Measurement of blood-oxygen saturation using a photoacoustic technique in the rabbit hypoxemia model.

The golden standard method to obtain accurate blood oxygen saturation is blood gas analysis that needs invasive procedure of blood sampling. Photoacoustic technique enables us to measure real-time blood oxygen saturation without invasive procedure. The aim of this study is to use the photoacoustic technique, an optical method, for accurately determining oxygen saturation in vivo. We measured induced photoacoustic signals of arterial blood in the rabbit model of stable hypoxemia after irradiation at 750 and 800 nm. Oxygen saturation was calculated from the photoacoustic signals using two calibration curves. Calibration curve 1 is a conventional curve derived from the absorbance coefficient of hemoglobin, whereas calibration curve 2 is derived from the photoacoustic signals obtained from the original blood vessel model. Simultaneously, blood-gas analysis was performed to obtain the reference standard of oxygen saturation. Regression analysis and Bland-Altman analysis were performed to assess the accuracy of oxygen saturation obtained using the two methods. The oxygen saturation calculated using calibration curves 1 and 2 showed strong correlations with the reference standard in regression analysis (R = 0.965, 0.964, respectively). The Bland-Altman analysis revealed better agreement and precision with calibration curve 2, whereas there was significant underestimation of values obtained using calibration curve 1. Photoacoustic measurement of oxygen saturation using calibration curve 2 provided an accurate estimate of oxygen saturation, which was similar to that obtained using a portable blood-gas analyzer.

Behavior of Nitrate-Nitrogen and Nitrite-Nitrogen in Drinking Water.

Nitrate-nitrogen (NO3-N) and nitrite-nitrogen (NO2-N) are constituents of the nitrogen cycle. NO3-N is toxic to humans, primarily due to its reduction to NO2-N. In Japan, NO3-N and NO2-N levels in tap water must not exceed 10 mg/L and only NO2-N alone not 0.04 mg/L, respectively. In this study, we verified the effect of microorganisms and ultraviolet (UV) to increase of NO2-N in water. First, all tested drinking-waters including tap water and commercial mineral water in PET bottles had < 2 mg/L NO3-N and undetectable levels (< 0.01 mg/L) of NO2-N. However, we found that NO2-N was generated in tap water left to stand at room temperature for several days, leading to increases in CF and TC counts and reduction of NO3-N. We also demonstrated that direct UV and sunlight irradiation of NO3-N-containing drinking water generated NO2-N in 1-2 h, with NO2-N reaching > 0.04 mg/mL by 4-6 h. On the other hand, NO3-N and NO2-N were undetectable in commercially purified water.