Retrospective study of thoracic endovascular aortic repair as a first-line treatment for traumatic blunt thoracic aortic injury.

OBJECTIVE: This study sought to confirm if thoracic endovascular aortic repair (TEVAR) was an appropriate therapeutic strategy for blunt thoracic aortic injury (BTAI). METHODS: Between 3/2005 and 12/2020, 104 patients with BTAI were brought to our hospital. The severity of each trauma case was evaluated using the Injury Severity Score (ISS); aortic injuries were classified as type I to IV according to Society for Vascular Surgery guidelines. Initial treatment was categorized into four groups: nonoperative management (NOM), open aortic repair (OAR), TEVAR, or emergency room thoracotomy/cardiopulmonary resuscitation (ERT/CPR). RESULTS: The patients' mean age and ISS were 56.7 ± 20.9 years and 48.3 ± 20.4, respectively. Type III or IV aortic injury were diagnosed in 82 patients. The breakdown of initial treatments was as follows: NOM for 28 patients, OAR for four, TEVAR for 47, and ERT/CPR for 25. The overall early mortality rate was 32.7%. Logistic regression analysis confirmed ISS > 50 and shock on admission as risk factors for early mortality. The cumulative survival rate of all patients was 61.2% at 5 years after treatment. After initial treatment, eight patients receiving TEVAR required OAR. The cumulative rate of freedom from reintervention using TEVAR at 5 years was higher in approved devices than in custom-made devices (96.0 vs. 56.3%, p = 0.011). CONCLUSIONS: Using TEVAR as an initial treatment for patients with BTAI is a reasonable approach. Patients with severe multiple traumas and shock on admission had poor early outcomes, and those treated with custom-made devices required significant rates of reintervention.

Risk Factors for Major Bleeding and Clinically Relevant Non-major Bleeding in Japanese Patients Treated with Edoxaban.

Edoxaban is used to prevent and treat stroke or systemic embolism such as venous thromboembolism. Although bleeding is the most common complication of anticoagulants, only a few studies have addressed the safety of direct oral anticoagulants in East Asian patients. In this study, we investigated the risk factors for bleeding in Japanese patients receiving edoxaban. A retrospective review of the records of 198 patients who received 30 mg/d edoxaban in our hospital between April 2015 and March 2017 was performed. Subsequently, these patients were followed up to 1 year. Seven (3.5%) and 22 (11.1%) patients developed major bleeding and clinically relevant bleeding, respectively. In the univariate Cox regression analyses, low baseline hemoglobin levels (p = 0.002) and low baseline creatinine clearance (p = 0.020) were significantly associated with major bleeding. Multivariate Cox regression analysis revealed that a low baseline hemoglobin level was a significant risk factor for major bleeding and clinically relevant bleeding [hazard ratio 1.67 per 1 g/dL decrease (95% confidence interval 1.14-2.56, p = 0.008) and hazard ratio 1.31 per 1 g/dL decrease (95% confidence interval 1.06-1.62, p = 0.013), respectively]. Baseline hemoglobin level in quartiles also showed a quartile-dependent decrease in major bleeding and clinically relevant bleeding event. These results suggest that low baseline hemoglobin level is a significant risk factor for both major bleeding and clinically relevant bleeding in Japanese patients receiving edoxaban. Thus, these patients should be carefully monitored.

Effect of the number of dose adjustment factors on bleeding risk in patients receiving 30 mg/day edoxaban.

WHAT IS KNOWN AND OBJECTIVE: Edoxaban has three dose adjustment factors (creatinine clearance, 15-50 mL/min; body weight, 60 kg or less; and concomitant medication with potent P-glycoprotein inhibitors) to prevent bleeding that results from elevated blood concentrations of the drug. A dose reduction (from 60 to 30 mg/day of edoxaban) is recommended for patients with even one of those. However, it is not clear whether 30 mg/day of edoxaban is adequate for patients with multiple dose adjustment factors. We thus investigated the association between the number of the dose adjustment factors and bleeding risk in patients receiving edoxaban. METHODS: We retrospectively analysed 198 patients who received 30 mg/day of edoxaban between April 2015 and March 2017 with follow-up for 1 year. RESULTS: The incidences of major bleeding were 1.4%, 7.3% and 20.0% in patients with 0-1, 2 and 3 dose adjustment factors, respectively. The Cox proportional hazards regression model revealed that the risk of major bleeding was higher in patients with 2 (hazard ratio [HR]: 5.80, 95% confidence interval [CI]: 0.96-44.05, P = .055) or 3 (HR: 17.70, 95% CI: 2.12-147.70, P = .012) dose adjustment factors than in those with 0-1 dose adjustment factor. WHAT IS NEW AND CONCLUSION: This is the first study to evaluate the risk of bleeding in patients administered 30 mg/day of edoxaban based on the number of dose adjustment factors in clinical practice. For patients receiving edoxaban, as the number of the dose adjustment factors increases, the risk of major bleeding is elevated. In patients with multiple dose adjustment factors, not only one level of dose reduction, but further dose reductions may be considered. Further studies with a larger sample size are needed to confirm these findings.

Astrocyte Activation in Locus Coeruleus Is Involved in Neuropathic Pain Exacerbation Mediated by Maternal Separation and Social Isolation Stress.

Our previous studies demonstrated that emotional dysfunction associated with early life stress exacerbated nerve injury-induced mechanical allodynia. Sex differences were observed in several anxiety tests, but not in mechanical allodynia. To elucidate the mechanism underlying these findings, we have now investigated the involvement of astrocytes in emotional dysfunction and enhancement of nerve injury-induced mechanical allodynia in mice subjected to maternal separation combined with social isolation (MSSI) as an early life stress. We measured expression of glial fibrillary acidic protein (GFAP), an astrocyte maker, in each brain area by immunohistochemistry. GFAP expression in the locus coeruleus (LC) of female, but not of male mice, significantly increased after MSSI, corresponding to the behavioral changes at 7 and 12 weeks of age. Lipopolysaccharide (LPS)-treated astrocyte-derived supernatant was administered to local brain regions, including LC. Intra-LC injection of conditioned medium from cultured astrocytes treated with LPS increased GFAP expression, anxiety-like behavior and mechanical allodynia in both male and female mice. Furthermore, increases in anxiety-like behavior correlated with increased mechanical allodynia. These findings demonstrate that emotional dysfunction and enhanced nerve injury-induced mechanical allodynia after exposure to MSSI are mediated, at least in part, by astrocyte activation in the LC. Male but not female mice may show resistance to MSSI stress during growth.

Effects of alkyl side chains and terminal hydrophilicity on vitamin D receptor (VDR) agonistic activity based on the diphenylpentane skeleton.

Vitamin D receptor (VDR) is a family of nuclear receptors (NR) that regulates physiological effects such as the immune system, calcium homeostasis, and cell proliferation. We synthesized non-secosteroidal VDR ligands bearing a long alkyl chain based on the diphenylpentane skeleton. The VDR-mediated transcriptional activities of the synthesized compounds were evaluated using a reporter gene assay and HL-60 cell differentiation-inducing assay. We herein described the structure-activity relationship and effects of alkyl-chain length on VDR-mediated transcriptional activity.

Sex differences in depression-like behavior after nerve injury are associated with differential changes in brain-derived neurotrophic factor levels in mice subjected to early life stress.

We recently demonstrated that exposure to early life stress exacerbates nerve injury-induced thermal and mechanical hypersensitivity in adult male and female mice. Accumulating evidence suggests that chronic pain causes emotional dysfunction, such as anxiety and depression. In the present study, we investigated the impact of early life stress on depression-like behavior after nerve injury in mice. In addition, we examined the expression of brain-derived neurotrophic factor (BDNF), which is known to be involved in the pathogenesis of depression. Early life stress was induced by maternal separation between 2 and 3 weeks of age combined with social isolation after weaning (MSSI). At 9 weeks of age, the sciatic nerve was partially ligated to elicit neuropathic pain. Depression-like behavior was evaluated using the forced swim test at 12 weeks of age. Tissue samples from different regions of the brain were collected at the end of maternal separation (3 weeks of age) or after the forced swim test (12 weeks of age). At 12 weeks of age, immobility time in the forced swim test was increased only in MSSI-stressed female mice with nerve injury. BDNF expression was increased in male, but not female, MSSI-stressed mice at 3 weeks of age. However, MSSI stress did not impact BDNF expression in male or female mice at 12 weeks of age. Our findings suggest that exposure to early life stress exacerbates emotional dysfunction induced by neuropathic pain in a sex-dependent manner. Changes in BDNF expression after early life stress may be associated with neuropathic pain-induced depression-like behavior in adulthood. Furthermore, sex differences in BDNF expression after exposure to early life stress may contribute to sex-specific susceptibility to neuropathic pain-induced emotional dysfunction.

Synthesis of cyclic 1-alkenylboronates via Zr-mediated double functionalization of alkynylboronates and sequential Ru-catalyzed ring-closing olefin metathesis.

Synthesis of novel cyclic 1-alkenylboronates is accomplished through the zirconium-mediated regio- and stereoselective double functionalization of 1-alkynylboronates and the subsequent ruthenium-catalyzed ring-closing metathesis (RCM). The obtained substituted cyclic 1-alkenylboronates are transformed into o-terphenyl and triphenylene derivatives.

The polarized carbon nanotube thin film LED.

We demonstrate a light emitting p-i-n diode made of a highly aligned film of separated (99%) semiconducting carbon nanotubes, self-assembled from solution. By using a split gate technique, we create p- and n-doped regions in the nanotube film that are separated by a micron-wide gap. We inject p- and n-type charge carriers into the device channel from opposite contacts and investigate the radiative recombination using optical micro-spectroscopy. We find that the threshold-less light generation efficiency in the intrinsic carbon nanotube film segment can be enhanced by increasing the potential drop across the junction, demonstrating the LED-principle in a carbon nanotube film for the first time. The device emits infrared light that is polarized along the long axes of the carbon nanotubes that form the aligned film.

Efficient narrow-band light emission from a single carbon nanotube p-n diode.

Electrically driven light emission from carbon nanotubes could be used in nanoscale lasers and single-photon sources, and has therefore been the focus of much research. However, high electric fields and currents have either been necessary for electroluminescence, or have been an undesired side effect, leading to high power requirements and low efficiencies. Furthermore, electroluminescent linewidths have been broad enough to obscure the contributions of individual optical transitions. Here, we report electrically induced light emission from individual carbon nanotube p-n diodes. A new level of control over electrical carrier injection is achieved, reducing power dissipation by a factor of up to 1,000, and resulting in zero threshold current, negligible self-heating and high carrier-to-photon conversion efficiencies. Moreover, the electroluminescent spectra are significantly narrower ( approximately 35 meV) than in previous studies, allowing the identification of emission from free and localized excitons.

Phonon populations and electrical power dissipation in carbon nanotube transistors.

Carbon nanotubes and graphene are candidate materials for nanoscale electronic devices. Both materials show weak acoustic phonon scattering and long mean free paths for low-energy charge carriers. However, high-energy carriers couple strongly to optical phonons, which leads to current saturation and the generation of hot phonons. A non-equilibrium phonon distribution has been invoked to explain the negative differential conductance observed in suspended metallic nanotubes, while Raman studies have shown the electrical generation of hot G-phonons in metallic nanotubes. Here, we present a complete picture of the phonon distribution in a functioning nanotube transistor including the G and the radial breathing modes, the Raman-inactive zone boundary K mode and the intermediate-frequency mode populated by anharmonic decay. The effective temperatures of the high- and intermediate-frequency phonons are considerably higher than those of acoustic phonons, indicating a phonon-decay bottleneck. Most importantly, inclusion of scattering by substrate polar phonons is needed to fully account for the observed electronic transport behaviour.

O2 release from Hb vesicles evaluated using an artificial, narrow O2-permeable tube: comparison with RBCs and acellular Hbs.

A phospholipid vesicle that encapsulates a concentrated hemoglobin (Hb) solution and pyridoxal 5'-phosphate as an allosteric effector [Hb vesicle (HbV) diameter, 250 nm] has been developed to provide an O2 carrying ability to plasma expanders. The O2 release from flowing HbVs was examined using an O2-permeable, fluorinated ethylenepropylene copolymer tube (inner diameter, 28 microm) exposed to a deoxygenated environment. Measurement of O2 release was performed using an apparatus that consisted of an inverted microscope and a scanning-grating spectrophotometer with a photon-count detector, and the rate of O2 release was determined based on the visible absorption spectrum in the Q band of Hb. HbVs and fresh human red blood cells (RBCs) were mixed in various volume ratios at a Hb concentration of 10 g/dl in isotonic saline that contained 5 g/dl albumin, and the suspension was perfused at the centerline flow velocity of 1 mm/s through the narrow tube. The mixtures of acellular Hb solution and RBCs were also tested. Because HbVs were homogeneously dispersed in the albumin solution, increasing the volume of the HbV suspension resulted in a thicker marginal RBC-free layer. Irrespective of the mixing ratio, the rate of O2 release from the HbV/RBC mixtures was similar to that of RBCs alone. On the other hand, the addition of 50 vol% of acellular Hb solution to RBCs significantly enhanced the rate of deoxygenation. This outstanding difference in the rate of O2 release between the HbV suspension and the acellular Hb solution should mainly be due to the difference in the particle size (250 vs. 7 nm) that affects their diffusion for the facilitated O2 transport.