Explore the vast range of titles available.

Divanillic acid (DVA)-based aromatic polyamides (PAs) consisting of DVA with linear (methyl, butyl, hexyl, and octyl groups) or branched (isopropyl and isobutyl groups) side chains and 4,4’-methyldianillin were synthesized as high-performance and ultra-high-performance biomass plastics. The DVA PAs were amorphous with high thermal stability (decomposition temperature of ca. 380 °C). The glass transition temperature ( T g ) of the DVA PAs depended on the side-chain composition in a linear manner, indicating the PA main chain possessed a random structure. The polymers were pressed to form melt-pressed films. The DVA PAs with a higher content of shorter side chains exhibited both higher T g and tensile strength than those of polymers with a lower content of shorter side chains. The PAs exhibited T g in the range of ca. 150–253 °C. The branched PA with isopropyl side chains exhibited the highest T g of 253 °C and highest tensile strength of 63 MPa among the DVA PAs. The PAs with isopropyl side chains and some linear side chains (methyl/hexyl combination) exhibited high tensile strength of approximately 60–70 MPa; however, their T g varied from 170 to 253 °C. The branched PA exhibited the highest T g , tensile strength, and Young’s modulus of the polymers. The thermal stability and mechanical properties of the PAs were tuned by their side-chain structure and composition.

Sodium-glucose transporter 2 (SGLT2) inhibitors are antidiabetic drugs affecting SGLT2. Recent studies have shown various cancers expressing SGLT2, and SGLT2 inhibitors attenuating tumor proliferation. We evaluated the antitumor activities of canagliflozin, a SGLT2 inhibitor, on glioblastoma (GBM). Three GBM cell lines, U251MG (human), U87MG (human), and GL261 (murine), were used. We assessed the expression of SGLT2 of GBM through immunoblotting, specimen-use, cell viability assays, and glucose uptake assay with canagliflozin. Then, we assessed phosphorylation of AMP-activated protein kinase (AMPK), p70 S6 kinase, and S6 ribosomal protein by immunoblotting. Concentrations of 5, 10, 20, and 40 μM canagliflozin were used in these tests. We also evaluated cell viability and immunoblotting using U251MG with siRNA knockdown of SGLT2. Furthermore, we divided the mice into vehicle group and canagliflozin group. The canagliflozin group was administrated with 100 mg/kg of canagliflozin orally for 10 days starting from the third days post-GBM transplant. The brains were removed and the tumor volume was evaluated using sections. SGLT2 was expressed in GBM cell and GBM allograft mouse. Canagliflozin administration at 40 μM significantly inhibited cell proliferation and glucose uptake into the cell. Additionally, canagliflozin at 40 μM significantly increased the phosphorylation of AMPK and suppressed that of p70 S6 kinase and S6 ribosomal protein. Similar results of cell viability assays and immunoblotting were obtained using siRNA SGLT2. Furthermore, although less effective than in vitro, the canagliflozin group significantly suppressed tumor growth in GBM-transplanted mice. This suggests that canagliflozin can be used as a potential treatment for GBM.

The prompt initiation of stroke treatment significantly influences patient outcomes, highlighting the crucial role of prehospital triage. This study aimed to assess the implementation of the 7-Item Japan Urgent Stroke Triage (JUST-7) score by emergency medical services (EMS) in our region and its effect on emergency transportation for suspected stroke patients. Data were collected from patients suspected of having an acute stroke with a Cincinnati Prehospital Stroke Scale (CPSS) score of 1 or more who were transferred by ambulance within 24 h of symptom onset. Two prehospital stroke scales were employed during different periods: period 1 with CPSS alone (January to December 2020) and period 2 with both CPSS and JUST-7 (January 2021 to March 2023). On-scene time data were obtained from the EMS crews, and data regarding the final diagnosis of patients and their outcomes were obtained from the respective hospitals to which the patients were transferred. These data were compared between periods 1 and 2 and between the CPSS and JUST-7. The results revealed that additional evaluation with JUST-7 did not affect ambulance transport time. The CPSS+JUST-7 approach demonstrated higher specificity in identifying stroke and major artery occlusion than with the CPSS alone; however, an appropriate cut-off value needs to be considered. The JUST-7 achieved a diagnostic concordance rate of 35.9% for the most likely stroke type and 64.0% for the first two most likely types. This research emphasizes the potential of JUST-7 as a valuable addition to prehospital stroke diagnosis protocols. Its flexibility in adapting cut-off values based on regional factors and available medical resources optimizes its utility in diverse healthcare settings. The JUST-7 score is a promising tool for improving patient outcomes through prompt and accurate prehospital assessments.

Polysaccharides are promising renewable alternatives to petroleum-based plastics, and are high-value-added materials in various industries. In this work, we synthesized dextran (α-1,6-glucan) ester derivatives substituting acyl groups with different carbon numbers from acetate to laurate. We found that the thermal stability of dextran was improved by esterification. Moreover, using differential scanning calorimetry and X-ray diffraction, we revealed that dextran ester derivatives were amorphous. Self-standing, transparent, solvent-cast films of dextran ester derivatives were prepared. Dextran ester derivatives adhered to various materials, including polyvinyl alcohol (PVA) films, wood, glass, and aluminum. In addition, the adhesive interfaces were transparent, which is important for practical applications. The adhesive strength for PVA films increased with concentration, exceeding the breaking strength of the PVA film at 0.3 g/mL. Moreover, dextran valerate and dextran hexanoate behaved as hot-melt-type adhesives. These results demonstrate the potential of dextran ester derivatives as biomass-based adhesives.

Confirming the antiplatelet effects of P2Y12 inhibitors is clinically important; although various methods exist for evaluating such antiplatelet effects, standard protocols are currently unavailable. We compared four platelet function tests in neuroendovascular patients performed based on two systems: (i) ADP-induced platelet aggregation level (APAL) and (ii) 10 µM ADP maximum aggregation (MA) using CN-6000, and (iii) P2Y12 reaction unit (PRU) as well as (iv) %inhibition using VerifyNow. Retrospective data of all 124 patients (median age 72 [26–92] years; 58.9% male) who received periprocedural antiplatelet therapy for elective neuroendovascular treatments between September 2020–December 2023 were evaluated. Blood samples were acquired the day before, immediately (1–3 days), and 1 month postoperatively, and during bleeding or thrombotic events. The results revealed changes over time in PRU, %inhibition, and APAL values, but not in 10 µM ADP MA. The correlation coefficient for PRU, the most widely used test in this setting, was higher with APAL ( r  = 0.55, p  < 0.01) than with 10 µM ADP MA ( r  = 0.42, p  < 0.01). An APAL result of 8.3 was equivalent to a PRU value of 240. In conclusion, APAL may provide more reliable monitoring of antiplatelet effects than 10 µM ADP MA-based monitoring and is worthy of further evaluation.

Background Tyrosine kinase inhibitors (TKIs) improve prognosis in chronic myeloid leukemia (CML). Nilotinib and ponatinib, second- and third-generation TKIs, respectively, have been reported to cause adverse vascular occlusive events such as myocardial infarction and peripheral arterial disease. However, little is known about the risk of cerebral infarction associated with severe cerebrovascular stenosis, which is a late complication of TKIs. Herein, we report two cases of cerebrovascular stenosis associated with TKIs for CML. Case presentation A 53-year-old man with CML experienced transient right-sided hemiparesis and dysarthria. The patient had been treated with ponatinib for 5 years. Digital subtraction angiography revealed diffuse stenosis with luminal narrowing from the terminal portion of the internal carotid artery (ICA) to the entire M1 length of the middle cerebral artery (MCA). He was diagnosed with hemodynamic cerebral ischemia due to severe intracranial ICA stenosis and underwent superficial temporal artery (STA)-MCA bypass surgery. He had no atherosclerotic factors or immunological serum markers such as vasculitis. As a side effect of TKI therapy was suspected, ponatinib therapy was discontinued. A 74-year-old man treated with nilotinib for CML presented with gait disturbances. Diffusion-weighted magnetic resonance imaging revealed multiple infarctions in the right cerebral hemisphere, and magnetic resonance angiography revealed severe bilateral intracranial ICA and MCA stenosis. The patient underwent a STA-MCA bypass surgery. We discontinued nilotinib treatment. The postoperative course was uneventful. Conclusions CML prognosis has steadily improved with the advent of new TKIs. In the future, reports of cerebrovascular stenosis caused by TKIs for CML may increase and systemic complications may become a problem. We should be aware that some TKIs may cause cerebrovascular stenosis.

BackgroundDual antiplatelet therapy (DAPT) is necessary to prevent thromboembolic complications after stent-assisted coiling (SAC) or flow-diversion (FD) for cerebral aneurysms, but the optimal antiplatelet regimen remains unclear.ObjectiveTo determine the optimal DAPT duration in patients with SAC/FD.MethodsThis multicenter cohort study enrolled patients who received SAC/FD for cerebral aneurysms at seven Japanese institutions between January 2010 and December 2020. The primary outcome was the time from procedure to the occurrence of a composite of target vessel-related thromboembolic events, procedure-unrelated major bleeding events, or death. The cumulative event-free survival rates were analyzed using a Kaplan–Meier curve, and the differences in each outcome between the groups dichotomized by the duration of DAPT were analyzed using the log-rank test.ResultsOf 632 patients (median observational period, 646 days), primary outcome occurred in 63 patients (10.0%), most frequently within 30 days after the procedure. The cumulative event-free survival rates at 30 days, 1 year, and 2 years after the procedure were 93.3% (91.4 to 95.3%), 91.5% (89.3 to 93.7%), and 89.5% (87.0 to 92.0%), respectively. The cumulative event-free survival rates after switching to monotherapy were similar for the >91 and <90 days DAPT groups in the population limited to patients who were switched from DAPT to monotherapy without major clinical events.ConclusionsThromboembolic events rarely occurred beyond 30 days after SAC/FD. The duration of DAPT may be shortened if patients have a periprocedural period without events. Further prospective studies are warranted to determine the optimal duration of antiplatelet therapy.Trial registration numberUMIN000044122 :https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000050384.

Regional cerebral blood flow (rCBF) quantification using 123I-N-isopropyl-p-iodoamphetamine (123I-IMP) requires an invasive, one-time-only arterial blood sampling for measuring the 123I-IMP arterial blood radioactivity concentration (Ca10). The purpose of this study was to estimate Ca10 by machine learning (ML) using artificial neural network (ANN) regression analysis and consequently calculating rCBF and cerebral vascular reactivity (CVR) in the dual-table autoradiography (DTARG) method. This retrospective study included 294 patients who underwent rCBF measurements through the 123I-IMP DTARG. In the ML, the objective variable was defined by the measured Ca10, whereas the explanatory variables included 28 numeric parameters, such as patient characteristic values, total injection 123I-IMP radiation dose, cross-calibration factor, and the distribution of 123I-IMP count in the first scan. ML was performed with training (n = 235) and testing (n = 59) sets. Ca10 was estimated in testing set by our proposing model. Alternatively, the estimated Ca10 was also calculated via the conventional method. Subsequently, rCBF and CVR were calculated using estimated Ca10. Pearson's correlation coefficient (r-value) for the goodness of fit and the Bland-Altman analysis for assessing the potential agreement and bias were performed between the measured and estimated values. The r-value of Ca10 estimated by our proposed model was higher compared with the conventional method (0.81 and 0.66, respectively). In the Bland-Altman analysis, mean differences of 4.7 (95% limits of agreement (LoA): -18-27) and 4.1 (95% LoA: -35-43) were observed using proposed model and the conventional method, respectively. The r-values of rCBF at rest, rCBF after the acetazolamide challenge, and CVR calculated using the Ca10 estimated by our proposed model were 0.83, 0.80 and 0.95, respectively. Our proposed ANN-based model could accurately estimate the Ca10, rCBF, and CVR in DTARG. These results would enable non-invasive rCBF quantification in DTARG.

Tramadol is a useful analgesic which acts as a serotonin and noradrenaline reuptake inhibitor in addition to μ-opioid receptor agonist. Cytoplasmic serotonin modulates the small GTPase activity through serotonylation, which is closely related to the human platelet activation. We recently reported that the combination of subthreshold collagen and CXCL12 synergistically activates human platelets. We herein investigated the effect and the mechanism of tramadol on the synergistic effect. Tramadol attenuated the synergistically stimulated platelet aggregation (300 μM of tramadol, 64.3% decrease, p<0.05). Not morphine or reboxetine, but duloxetine, fluvoxamine and sertraline attenuated the synergistic effect of the combination on the platelet aggregation (30 μM of fluvoxamine, 67.3% decrease, p<0.05; 30 μM of sertraline, 67.8% decrease, p<0.05). The geranylgeranyltransferase inhibitor GGTI-286 attenuated the aggregation of synergistically stimulated platelet (50 μM of GGTI-286, 80.8% decrease, p<0.05), in which GTP-binding Rac was increased. The Rac1-GEF interaction inhibitor NSC23766 suppressed the platelet activation and the phosphorylation of p38 MAPK and HSP27 induced by the combination of collagen and CXCL12. Tramadol and fluvoxamine almost completely attenuated the levels of GTP-binding Rac and the phosphorylation of both p38 MAPK and HSP27 stimulated by the combination. Suppression of the platelet aggregation after the duloxetine administration was observed in 2 of 5 patients in pain clinic. These results suggest that tramadol negatively regulates the combination of subthreshold collagen and CXCL12-induced platelet activation via Rac upstream of p38 MAPK.

Background Dual antiplatelet therapy (DAPT) is necessary for stent assisted coiling. However, long term use of DAPT has a potential risk of hemorrhagic events. We aimed to examine the relationship between clopidogrel reactivity and complications. Methods Patients who underwent stent assisted coiling for unruptured aneurysms or previously treated aneurysms and received periprocedural DAPT in our institution between August 2011 to March 2020 were included. Platelet reactivity for clopidogrel was measured by VerifyNow assay system, and we defined the cut off value of P2Y12 Reaction Units (PRU) at 208 and classified patients as hypo-responders (PRU≧208) or responders (PRU<208). The rates of hemorrhagic and thrombotic events within 30 days (acute phase) and 30 days after the procedure (delayed phase) were compared between the two groups. Furthermore, changes in hemoglobin levels were measured before and after the procedure and at chronic stages (1 to 6 months thereafter). Results From 61 patients included in this study, 36 patients were hypo-responders and 25 patients were responders. Hemorrhagic events occurred 8.0% only in responders in the acute phase ( p  = 0.16), and 2.78% in hypo-responders and 20.0% in responders in the delayed phase ( p  = 0.037). Changes in hemoglobin levels before and after the procedure were 1.22 g/dl in hypo-responders and 1.74 g/dl in responders ( p  = 0.032) while before the procedure and chronic stages they were 0.39 g/dl in hypo-responders and 1.39 g/dl in responders ( p  <  0.01). Thrombotic events were not significantly different between the two groups. Conclusion Long term use of DAPT after stent assisted coiling is related to hemorrhagic events in the delayed phase. Preventing for hemorrhagic events, the duration of DAPT should be carefully considered in clopidogrel responders.