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This paper ascertains that the bilinear shock Hugoniot equation of state (EOS) can model the plasticizing process of the porous media like concrete material for high-velocity impact problems successfully. The negative slope of the bilinear Hugoniot for low particle velocity regime can simulate the process that the porosity of concrete may be compressed to form shock wave in concrete, through a series of numerical analyses over the investigation on the physical phenomena. The results of particle velocity for the concrete material are also discussed to be compared with those of non-porous aluminum alloy for 100 and 1000 m/s impact velocities. All the numerical simulations were carried out by applying the bilinear shock Hugoniot EOS to concrete which was linked to the binary object of a hydrocode: ANSYS Autodyn®[1−3] through a user’s subroutine.

Abstract To investigate dysphagia after extubation in patients with severe coronavirus disease 2019 (COVID-19). We retrospectively examined patients with severe COVID-19 treated in our hospital between August 2021 and March 2022. Feeding outcomes were categorized into two groups—(1) total oral intake, and (2) difficulty in oral intake. To assess the feeding outcome, we used modified water-swallowing test (MWST) for all patients. However, in cases where aspiration or recurrent laryngeal nerve palsy was suspected, we conducted the fiberoptic endoscopic evaluation of swallowing after MWST. Patient data were collected from medical records. Forty-six patients with severe COVID-19 were included. Among the 46 patients, 14 (30.4%) experienced difficulties with oral intake. Older age, longer length of hospitalization, duration of mechanical ventilation, tracheostomy, diabetes, and higher serum levels of C-reactive protein (CRP) and procalcitonin (PCT) at the time of intubation were associated with difficulty in oral intake. The rate of difficulty with oral intake in patients with severe COVID-19 was 30.4%, which is not as high as reported in previous studies. Older age, longer duration of mechanical ventilation, tracheostomy, diabetes, and higher levels of CRP and PCT were associated with the prevalence of oral intake difficulty, suggesting that early attention should be paid to high-risk patients who have preexisting deterioration of swallowing function due to aging and comorbidities, or who have prolonged intubation or tracheostomy to prevent aspiration pneumonia.

Summary: In this study, a murine sepsis model was developed using the cecum ligation and puncture (CLP) technique. The expression of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) in the brain increased 6 h after CLP but decreased 24 h later when elevated endogenous dopamine levels in the brain were sustained. Methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride reduced dopamine levels in the striatum and increased mortality in septic mice. Dopamine D1-like receptors were significantly expressed in the brain, but not in the lungs. Intraperitoneally administered SKF-81297 (SKF), a blood-brain barrier-permeable D1-like receptor agonist, prevented CLP-induced death of septic mice with ameliorated acute lung injury and cognitive dysfunction and suppressed TNF-α and IL-1β expression. The D1-like receptor antagonist SCH-23390 abolished the anti-inflammatory effects of SKF. These data suggest that D1-like receptor-mediated signals in the brain prevent CLP-induced inflammation in both the brain and the periphery.

Abstract Objectives Laryngeal complications have been reported after endotracheal intubation and prone positioning in patients with critical coronavirus disease 2019 (COVID‐19), but their association is unclear. In this study, we investigated the rate of laryngeal complications in patients with COVID‐19 compared to an alternative condition (control group). Methods We retrospectively analyzed the data of 40 patients who underwent endotracheal intubation for either COVID‐19 or an alternative condition (control group). Data on age, sex, body mass index (BMI), cardiovascular disease (CVD) risk factors, use of prone therapy, duration of endotracheal intubation, and duration from extubation/tracheostomy to laryngeal evaluation were collected from medical records. Results There were no significant differences in BMI, frequency of CVD risk factors, duration of endotracheal intubation, or duration from extubation/tracheostomy to laryngeal evaluation between the two groups. In the COVID‐19 group, all patients adopted the prone position. In comparison, only one patient in the control group adopted the prone position. Significant differences were observed between the two groups regarding the incidence of vocal fold immobility and laryngeal granuloma. Conclusion Laryngeal complications were more common in the COVID‐19 group than in the control group. Prone positioning may be a risk factor for these complications. Level of Evidence 4.

BackgroundTracheostomy is an important procedure for the treatment of severe coronavirus disease-2019 (COVID-19). Older age and obesity have been reported to be associated with the risk of severe COVID-19 and prolonged intubation, and anticoagulants are often administered in patients with severe COVID-19; these factors are also related to a higher risk of tracheostomy. Cricotracheostomy, a modified procedure for opening the airway through intentional partial cricoid cartilage resection, was recently reported to be useful in cases with low-lying larynx, obesity, stiff neck, and bleeding tendency. Here, we investigated the usefulness and safety of cricotracheostomy for severe COVID-19 patients.Materials and methodsFifteen patients with severe COVID-19 who underwent cricotracheostomy between January 2021 and April 2022 with a follow-up period of ≥ 14 days were included in this study. Forty patients with respiratory failure not related to COVID-19 who underwent traditional tracheostomy between January 2015 and April 2022 comprised the control group. Data were collected from medical records and comprised age, sex, body mass index, interval from intubation to tracheostomy, use of anticoagulants, complications of tracheostomy, and decannulation.ResultsAge, sex, and days from intubation to tracheostomy were not significantly different between the COVID-19/cricotracheostomy and control/traditional tracheostomy groups. Body mass index was significantly higher in the COVID-19 group than that in the control group (P = 0.02). The rate of use of anticoagulants was significantly higher in the COVID-19 group compared with the control group (P

Hypothesis: This study aimed to investigate the results, indications, and limitations of absorbable pin fixation for osteochondritis dissecans of the humeral capitellum in the separation stage. Methods: This study included 35 patients (mean age, 14.0 years). Patients were divided into two groups: Group A included those who obtained complete union within 6 months and Group B included those who did not observe complete union within 6 months. The clinical findings were compared between the groups. Results: There were 26 and 6 patients in Groups A and B, respectively. Two patients did not obtain complete union. Clinical outcomes improved after the procedure. In univariate analysis, delayed union was associated with larger major diameter (P = .0004) and more depth (P = .03) of the osteochondral fragment measured by computed tomography, the presence of osteosclerosis in the subchondral bed on X-ray imaging (P = .003), and the presence of comminution of subchondral bone on ultrasound imaging (P = .01). In multivariate analysis, there was a significant difference only in the major diameter of the osteochondral fragment (P = .03). Receiver operating characteristic curves analysis shows that if the major diameter of the osteochondral fragment is 11 mm or less, 85% of patients achieve complete union of the osteochondral fragments within 6 months. Conclusion: Absorbable pin fixation may be considered for the osteochondral fragments with major diameter of 11 mm or less and should not be considered for patients who demonstrate osteosclerosis in the subchondral bed or comminution of subchondral bone.

Abstract Background We conducted a prospective observational study for investigating the changes in the 13th member of a disintegrin-like and metalloprotease with thrombospondin type 1 motif (ADAMTS13) and its association with the coagulofibrinolytic response in adult trauma patients. Methods In 39 trauma patients hospitalized for longer than 7 days, time-course changes in biomarkers of coagulofibrinolysis and systemic inflammation along with ADAMTS13 activity were examined. The patients were stratified into three groups based on ADAMTS13 activities on admission (day 0): normal group (≥70%), mildly decreased group (≥50 and

Abstract Background Heat stroke induces coagulofibrinolytic activation, which leads to life-threatening disseminated intravascular coagulation (DIC). However, treatment strategies for DIC in heat stroke have not yet been established, and also, the time course changes in coagulofibrinolytic markers have not been thoroughly evaluated. We report a severe heat stroke case with DIC who was eventually saved by anti-DIC treatments in accordance with changes in coagulofibrinolytic markers. Case presentation A 45-year-old man was found unconscious outside, and his body temperature was elevated to 41.9 °C. For heat stroke, we performed an immediate tracheal intubation under the general anesthesia along with cooling by iced gastric lavage, cold fluid administration, and an intravascular cooling using Thermogard™. About 4 h after admission, his core temperature fell to 37 °C. We assessed coagulofibrinolytic biomarkers and treated in accordance with changes in these parameters. This case exhibited a biphasic change varying from an enhanced to a suppressed fibrinolytic type of DIC depending on the relative balance between fibrinolytic activation and the level of plasminogen activator inhibitor-1 (PAI-1). In the early phase with consumption coagulopathy and enhanced fibrinolysis, we transfused a large amount of fresh frozen plasma (FFP) and platelets with tranexamic acid, an antifibrinolytic agent, possibly providing relief for the bleeding tendency. Anticoagulant therapy using recombinant human thrombomodulin-α (rh-TM-α) and antithrombin III (ATIII) concentrate was especially effective for DIC with a suppressed fibrinolytic phenotype in the later phase, after which organ failure that included severe hepatic failure was remarkably improved. Conclusion The present case may indicate the clinical significance of monitoring coagulifibrinolytic changes and the potential benefits of anticoagulants for heat stroke-induced DIC.

Abstract Background Acetabular retroversion is a rotatory abnormality of the entire hemipelvis that includes anterior over-coverage and posterior deficiency of the acetabulum, and is associated with pincer-type femoroacetabular impingement and posterior hip instability. Acetabular retroversion is thought to cause posterior dislocation of the hip in athletes due to both the pincer-type femoroacetabular impingement and posterior hip instability. Case presentation A 26-year-old Japanese man had acetabular retroversion that induced recurrent posterior dislocation of his hip due to excessive hip flexion while wakeboarding. We performed anteverting eccentric rotational acetabular osteotomy using preoperative three-dimensional planning and an intraoperative computerized navigation system. Our patient was able to return to sports activities 1 year postoperatively. Conclusions Both preoperative three-dimensional surgical planning software and an intraoperative navigation system can provide a highly accurate map for this complicated surgery that simultaneously improves the pincer-type femoroacetabular impingement and posterior deficiency of the acetabulum.

Abstract Background We conducted a prospective observational study for investigating coagulofibrinolytic changes and mechanisms of antithrombin (AT) alternations in trauma. Methods Trauma patients hospitalized for more than seven days were analyzed for coagulofibrinolytic biomarkers. The patients were stratified into two groups according to AT activity level on admission (day 0), comprising normal AT and low AT patients. Results Thirty-nine patients (median Injury Severity Score 20) exhibited initial coagulatory activation and triphasic fibrinolytic changes. AT activity did not show a negative linear correlation with levels of thrombin-antithrombin complex (TAT), a marker of coagulation activity and AT consumption, but was strongly correlated with levels of albumin (Alb), an index of vascular permeability, on day 0 (r = 0.702, p

Abstract Background We conducted a questionnaire survey of shipyard workers to identify difficulties experienced due to orthopedic or musculoskeletal disorders. Methods The subjects were 375 workers (male, 361; female, 14) who worked for a single shipbuilding company. Questionnaire items covered the working environment, including work environment, working posture, and the weight of objects that the subject dealt with, as well as physical and lifestyle characteristics, namely smoking habits, drinking habits, sleeping hours, medications, exercise habits, and any weight gain of 20 kg or more since the age of 20. Subjects were also asked to indicate if they regularly experienced any of 17 listed difficulties in their daily lives, and to use an illustration of the human body to mark any body parts that were painful or hard to move. Results The mean age was 41.8 years (19–73 years). The lower and/or upper back was the most frequent site of pain (46.5%), followed by the shoulders (11.4%), knees (9.6%), and neck (5.3%). Maintaining a half-sitting posture was the most problematic activity of daily living. Back pain was less frequent in subjects who exercised regularly, and more common in those who worked with heavy loads or in narrow spaces. A multinomial logistic regression analysis showed that absence from work was more common in subjects with back pain who had gained weight since their youth, who smoked, who used fire while welding metal, or who worked in a lying posture. While 35.4% of subjects had experienced absence from work due to musculoskeletal pain, only 5.1% were permitted by their employer to alter their work content or reduce their workload. Conclusions These results indicate that a large number of shipyard workers have difficulties in their work and daily life activities due to back pain. To prevent worsening of pain and to reduce work absence, it is important to provide appropriate training to minimize the risk factors for back pain that were identified in this study.

We studied the H2 column density probability distribution function (N-PDF) based on molecular emission lines using the Nobeyama 45-m Cygnus X CO survey data. Using the DENDROGRAM and SCIMES algorithms, we identified 124 molecular clouds in the 13CO data. From these identified molecular clouds, an N-PDF was constructed for 11 molecular clouds with an extent of more than 0.4 deg2. From the fitting of the N-PDF, we found that the N-PDF could be well fitted with one or two lognormal distributions. These fitting results provided an alternative density structure for molecular clouds from a conventional picture. We investigated the column density, dense molecular cloud cores, and radio continuum source distributions in each cloud and found that the N-PDF shape was less correlated with the star-forming activity over a whole cloud. Furthermore, we found that the lognormal N-PDF parameters obtained from the fitting showed two impressive features. First, the lognormal distribution at the low-density part had the same mean column density (∼1021.5 cm−2) for almost all the molecular clouds. Second, the width of the lognormal distribution tended to decrease with an increasing mean density of the structures. These correlations suggest that the shape of the N-PDF reflects the relationship between the density and turbulent structure of the whole molecular cloud but is less affected by star-forming activities. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to evaluate the association between endotheliopathy represented by high levels of circulating syndecan-1 (SDC-1) and coagulofibrinolytic responses due to trauma, which can lead to disseminated intravascular coagulation (DIC). Methods: We retrospectively evaluated 48 eligible trauma patients immediately admitted to our hospital and assessed SDC-1 and coagulofibrinolytic parameters for 7 days after admission. We compared the longitudinal changes of coagulofibrinolytic parameters and SDC-1 levels between two groups (high and low SDC-1) according to median SDC-1 value on admission. Results: The median circulating SDC-1 level was 99.6 (61.1–214.3) ng/mL on admission, and levels remained high until 7 days after admission. Coagulofibrinolytic responses assessed by biomarkers immediately after trauma were correlated with SDC-1 elevation (thrombin–antithrombin complex, TAT: r = 0.352, p = 0.001; antithrombin, AT: r = −0.301, p < 0.001; plasmin-α2-plasmin inhibitor complex, PIC: r = 0.503, p = 0.035; tissue plasminogen activator, tPA: r = 0.630, p < 0.001). Sustained SDC-1 elevation was associated with intense and prolonged coagulation activation, impairment of anticoagulation, and fibrinolytic activation followed by inhibition of fibrinolysis, which are the primary responses associated with development of DIC in the acute phase of trauma. Elevation of circulating SDC-1 level was also associated with consumption coagulopathy and the need for transfusion, which revealed a significant association between high SDC-1 levels and the development of DIC after trauma (area under the curve, AUC = 0.845, cut-off value = 130.38 ng/mL, p = 0.001). Conclusions: High circulating levels of syndecan-1 were associated with intense and prolonged coagulation activation, impairment of anticoagulation, fibrinolytic activation, and consumption coagulopathy after trauma. Endotheliopathy represented by SDC-1 elevation was associated with trauma induced coagulopathy, which can lead to the development of DIC. [ABSTRACT FROM AUTHOR]

We studied the probability distribution function of the column density (N-PDF) of molecular clouds based on a fit with a multi-log-normal function using the Nobeyama 45-m Cygnus X CO survey data. We identified 124 molecular clouds in 13CO data using the DENDROGRAM and SCIMES algorithms. The N-PDF was constructed for 11 extended (≥ 0.4 deg2) molecular clouds of these identified clouds. We found that every N-PDF is well-fitted with one or two log-normal (LN) distributions. We investigated the distributions of the column density, C18O dense cores, and radio continuum source in each cloud and found that the N-PDF was less correlated with the star-forming activity. The LN N-PDF parameters showed two impressive features. First, the LN distribution at the low-density part had the same mean column density (∼1021.5 cm−2) for almost all the molecular clouds. Second, the wider LN distribution tended to show the lower mean density of the structures. [ABSTRACT FROM AUTHOR]

Abstract.: The thienopyridine derivative ticlopidine (TCL) is an inhibitor of adenosine diphosphate-induced platelet aggregation. Combination therapy with a thienopyridine derivative and aspirin is standard after coronary stenting, although more hemorrhagic complications occur with the combination therapy than with aspirin alone. A proton pump inhibitor (PPI) is required for prevention or treatment of upper gastrointestinal bleeding in such cases. We examined the effects of PPIs [omeprazole (OPZ) and rabeprazole (RPZ)] on TCL metabolism using pooled human liver microsomes prepared from various human liver blocks and 12 individual human liver microsomes. We calculated the Ki values of each PPI for TCL metabolic activity and compared the inhibitory effect of each PPI on TCL metabolism. The Ki values of OPZ and RPZ were 1.4 and 12.7 μM, respectively. The inhibitory effect of OPZ (78.6 ± 0.05%) was significantly greater than that of RPZ (24.2 ± 0.05%) (P < 0.001). Interestingly, a negative correlation existed between the inhibitory effect of OPZ and CYP2C19 activity (r = −0.909, P < 0.001). These results suggest that the inhibitory effect of OPZ is more potent than that of RPZ in vitro. In conclusion, RPZ appears preferable when administering TCL, aspirin, and a PPI in combination. Keywords:: ticlopidine, proton-pump inhibitor, drug–drug interaction, clopidogrel, cytochrome P450 (CYP) 2C19

The aim of this study was to determine suitable culture conditions for maintaining the activity of cytochrome p450 (CYP) 3A4 and drug transporters in primary cultured human hepatocytes. Human hepatocytes were isolated using the two-step collagenase perfusion technique and were cultured with four different media, serum-free William’s E medium (serum-free WEM), WEM containing fetal calf serum (FCS-WEM), WEM with human serum (HS-WEM), and Lanford’s medium. The albumin levels were maintained for 7 days in hepatocytes. Although CYP3A4 mRNA levels gradually decreased from 3 days, CYP3A4 and hepatocyte nuclear factor-4α alpha protein levels and activities were maintained for 7 days in hepatocytes cultured with serum-free WEM and Lanford’s but not in those with FCS-WEM and HS-WEM. Furthermore, CYP3A4 protein levels were significantly increased by the addition of rifampicin and dexamethasone to the culture media, indicating that the induction potential was maintained. The protein levels of P-glycoprotein, multi-drug-resistance-2, and breast cancer-resistance protein were maintained for 7 days in all media. Serum-free WEM and Lanford’s also maintained protein levels of CYP2C19, CYP2D6, and organic anion transporter polypeptide in the hepatocytes. Serum-free WEM and Lanford’s may be appropriate culture media for maintaining CYP3A4 and drug transporter protein levels in primary cultured hepatocytes. Keywords:: CYP3A4, HNF-4α, primary hepatocyte, ATP-binding cassette transporter, Lanford’s medium

Adipose tissue contains multipotent cells known as adipose-derived stem/stromal cells (ASCs), which have therapeutic potential for various diseases. Although the demand for adipose tissue for research use remains high, no adipose tissue bank exists. In this study, we attempted to isolate ASCs from cryopreserved adipose tissue with the aim of developing a banking system. ASCs were isolated from fresh and cryopreserved adipose tissue of rats and compared for proliferation (doubling time), differentiation capability (adipocytes), and cytokine (hepatocyte growth factor and vascular endothelial growth factor) secretion. Finally, ASCs (2.5 × 106) were intravenously infused into rats with spinal cord injury, after which hindlimb motor function was evaluated. Isolation and culture of ASCs from cryopreserved adipose tissue were possible, and their characteristics were not significantly different from those of fresh tissue. Transplantation of ASCs derived from cryopreserved tissue significantly promoted restoration of hindlimb movement function in injured model rats. These results indicate that cryopreservation of adipose tissue may be an option for clinical application.

We investigated the effects of prenatal dexamethasone (DEX) administration on antioxidant enzymes (AOEs) and nitric oxide synthase (NOS) in fetal and neonatal rat lungs. DEX (1 mg/kg, s.c., for 2 days) or vehicle alone was administered to pregnant rats, and the lungs of fetuses on days 19 and 21 of gestation and of 1- and 3-day-old neonates were examined. We measured protein levels of the AOEs manganese superoxide dismutase and copper-zinc super-oxide dismutase (Mn SOD and Cu-Zn SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and inducible and endothelial nitric oxide synthase (i-NOS and e-NOS). Mn SOD, GSH-Px, and e-NOS expression gradually increased with increasing gestational and postnatal age in the lungs of the control groups. Cu-Zn SOD, CAT, and i-NOS expression did not change with increasing gestational and postnatal age in the lungs of the control groups. DEX administration had significant effects on i-NOS and e-NOS protein and mRNA expression. The increased Mn SOD, GSH-Px, and e-NOS expressions during the perinatal period suggests that antenatal developmental changes in AOEs in the lungs of premature fetuses could be reduced by reactive oxygen species–mediated injury at birth. Furthermore, antenatal glucocorticoid treatment may accelerate the development of lungs via the two types of NOS. Keywords:: reactive oxygen species, antioxidant enzyme, dexamethasone, superoxide dismutase, nitric oxide synthase

The topoisomerase I inhibitor irinotecan is widely used in anticancer therapy, although the detailed mechanism is still unclear. We investigated the apoptotic mechanisms of irinotecan in human hepatocellular carcinoma (HCC) cell lines (Huh7). SN-38 caused a significant decrease in cell proliferation and induced apoptosis in Huh7 cells and HepG2 cells. SN-38 significantly increased the expression of p53 protein and its phosphorylation at Ser15 in the nucleus and apoptosis-inducing proteins Bax, caspase-9, and caspase-3, while it significantly decreased the antiapoptosis protein Bcl-xL of Huh7 cells. SN-38-induced apoptosis was recovered after p53 antisense oligodeoxynucleotide (AS ODN) pretreatment, while Huh7 cells were precultured with p53 AS ODN, followed by the addition of SN-38 for 24 h. Furthermore, increases in p53 DNA-binding activity were observed in the nuclei of Huh7 cells after SN-38 treatment as shown by electrophoretic mobility shift analysis. SN-38 binding motifs were detected in the proximal promoter of p53 (bases −433 to −317 and −814 to −711). These results suggest that the p53-mediated apoptosis pathway is important in the anticancer effects of irinotecan in hepatocellular carcinoma. Keywords:: irinotecan, SN-38, Huh7 cell, apoptosis, p53 gene

Objectives: Laryngeal complications have been reported after endotracheal intubation and prone positioning in patients with critical coronavirus disease 2019 (COVID‐19), but their association is unclear. In this study, we investigated the rate of laryngeal complications in patients with COVID‐19 compared to an alternative condition (control group). Methods: We retrospectively analyzed the data of 40 patients who underwent endotracheal intubation for either COVID‐19 or an alternative condition (control group). Data on age, sex, body mass index (BMI), cardiovascular disease (CVD) risk factors, use of prone therapy, duration of endotracheal intubation, and duration from extubation/tracheostomy to laryngeal evaluation were collected from medical records. Results: There were no significant differences in BMI, frequency of CVD risk factors, duration of endotracheal intubation, or duration from extubation/tracheostomy to laryngeal evaluation between the two groups. In the COVID‐19 group, all patients adopted the prone position. In comparison, only one patient in the control group adopted the prone position. Significant differences were observed between the two groups regarding the incidence of vocal fold immobility and laryngeal granuloma. Conclusion: Laryngeal complications were more common in the COVID‐19 group than in the control group. Prone positioning may be a risk factor for these complications. Level of Evidence: 4. [ABSTRACT FROM AUTHOR]

This paper reports on four of the sources observed in the KAGONMA (KAgoshima Galactic Object survey with the Nobeyama 45-m telescope by Mapping in Ammonia lines) project for which mapping observations have been completed (KAG35, KAG45, KAG64, and KAG71). In this study, we compiled the analysis results of four sources for which mapping observations were completed in the KAGONMA project and statistically investigated the range to which star formation activity affects the molecular gas. In order to investigate the affected range, we analyzed the heating range by focusing on the temperature distribution of the molecular cloud and found that it is within about 3 pc. This suggests that direct star formation feedback in molecular clouds is very spatially limited. [ABSTRACT FROM AUTHOR]