A mouse xenograft long-term replication yields a SARS-CoV-2 Delta mutant with increased lethality.

We recently established a long-term SARS-CoV-2 infection model using lung-cancer xenograft mice and identified mutations that arose in the SARS-CoV-2 genome during long-term propagation. Here, we applied our model to the SARS-CoV-2 Delta variant, which has increased transmissibility and immune escape compared with ancestral SARS-CoV-2. We observed limited mutations in SARS-CoV-2 Delta during long-term propagation, including two predominant mutations: R682W in the spike protein and L330W in the nucleocapsid protein. We analyzed two representative isolates, Delta-10 and Delta-12, with both predominant mutations and some additional mutations. Delta-10 and Delta-12 showed lower replication capacity compared with SARS-CoV-2 Delta in cultured cells; however, Delta-12 was more lethal in K18-hACE2 mice compared with SARS-CoV-2 Delta and Delta-10. Mice infected with Delta-12 had higher viral titers, more severe histopathology in the lungs, higher chemokine expression, increased astrocyte and microglia activation, and extensive neutrophil infiltration in the brain. Brain tissue hemorrhage and mild vacuolation were also observed, suggesting that the high lethality of Delta-12 was associated with lung and brain pathology. Our long-term infection model can provide mutant viruses derived from SARS-CoV-2 Delta and knowledge about the possible contributions of emergent mutations to the properties of new variants.

Radotinib Decreases Prion Propagation and Prolongs Survival Times in Models of Prion Disease.

The conversion of cellular prion protein (PrPC) into pathogenic prion isoforms (PrPSc) and the mutation of PRNP are definite causes of prion diseases. Unfortunately, without exception, prion diseases are untreatable and fatal neurodegenerative disorders; therefore, one area of research focuses on identifying medicines that can delay the progression of these diseases. According to the concept of drug repositioning, we investigated the efficacy of the c-Abl tyrosine kinase inhibitor radotinib, which is a drug that is approved for the treatment of chronic myeloid leukemia, in the treatment of disease progression in prion models, including prion-infected cell models, Tga20 and hamster cerebellar slice culture models, and 263K scrapie-infected hamster models. Radotinib inhibited PrPSc deposition in neuronal ZW13-2 cells that were infected with the 22L or 139A scrapie strains and in cerebellar slice cultures that were infected with the 22L or 263K scrapie strains. Interestingly, hamsters that were intraperitoneally injected with the 263K scrapie strain and intragastrically treated with radotinib (100 mg/kg) exhibited prolonged survival times (159 ± 28.6 days) compared to nontreated hamsters (135 ± 9.9 days) as well as reduced PrPSc deposition and ameliorated pathology. However, intraperitoneal injection of radotinib exerted a smaller effect on the survival rate of the hamsters. Additionally, we found that different concentrations of radotinib (60, 100, and 200 mg/kg) had similar effects on survival time, but this effect was not observed after treatment with a low dose (30 mg/kg) of radotinib. Interestingly, when radotinib was administered 4 or 8 weeks after prion inoculation, the treated hamsters survived longer than the vehicle-treated hamsters. Additionally, a pharmacokinetic assay revealed that radotinib effectively crossed the blood-brain barrier. Based on our findings, we suggest that radotinib is a new candidate anti-prion drug that could possibly be used to treat prion diseases and promote the remission of symptoms.

Impact of vertical stratification on the 2020 spring bloom in the Yellow Sea.

The Yellow Sea is one of the world's most abundant marine resources, providing food and economic benefits to the Korean and Chinese populations. In spring 2020, a decrease in the intensity of phytoplankton bloom was observed. While one study attributed this decline to a decrease in nutrient associated with the COVID-19 pandemic, our previous research proposed weakened thermal stratification accompanied by a surface cooling anomaly as the cause. However, the relationship between the marine environment and ecosystem has not been fully elucidated. Using observations and marine physical-biogeochemical model data, we identified the weakened stratification as a critical factor for suppressing the 2020 spring bloom. Intense vertical mixing hindered the accumulation of nutrient and chlorophyll-a concentrations within the euphotic zone, resulting in a diminished phytoplankton bloom. In contrast, reduced nitrate and phosphate concentrations in 2020 were insignificant compared to those in 2017-2019, despite the notable decline in PM2.5 in March 2020 due to COVID-19. In April 2020, nutrient levels fell within the range of interannual variability based on long-term observations, reflecting a negligible effect on the spring phytoplankton bloom. Our findings provide insight into the importance of marine physical factors on the phytoplankton biomass in the Yellow Sea.

Synthesis and anti-prion aggregation activity of acylthiosemicarbazide analogues.

Prions are infectious protein particles known to cause prion diseases. The biochemical entity of the pathogen is the misfolded prion protein (PrPSc) that forms insoluble amyloids to impair brain function. PrPSc interacts with the non-pathogenic, cellular prion protein (PrPC) and facilitates conversion into a nascent misfolded isoform. Several small molecules have been reported to inhibit the aggregation of PrPSc but no pharmacological intervention was well established thus far. We, here, report that acylthiosemicarbazides inhibit the prion aggregation. Compounds 7x and 7y showed almost perfect inhibition (EC50 = 5 µM) in prion aggregation formation assay. The activity was further confirmed by atomic force microscopy, semi-denaturing detergent agarose gel electrophoresis and real-time quaking induced conversion assay (EC50 = 0.9 and 2.8 µM, respectively). These compounds also disaggregated pre-existing aggregates in vitro and one of them decreased the level of PrPSc in cultured cells with permanent prion infection, suggesting their potential as a treatment platform. In conclusion, hydroxy-2-naphthoylthiosemicarbazides can be an excellent scaffold for the discovery of anti-prion therapeutics.

Causes for an extreme cold condition over Northeast Asia during April 2020.

Although 2020 was the fourth warmest year on record in northern Asia, the cold condition in April 2020 caused severe damage to the agricultural and marine ecosystems in northeastern Asia. Previous studies have indicated that the dipole atmospheric circulation over Siberia and the East Sea (Japan Sea) produced this cold environment with strong northwesterly wind. However, the potential causes of the dipole circulation over northeastern Asia remain unclear. In this study, we found that the East Atlantic/Western Russia (EAWR) pattern and blocking combined to produce the atmospheric structure. The wave train originated from the vorticity forcing of northwestern/central Russia and propagated from Western Europe to the East Sea via the background westerly and northerly winds. In addition, the Siberian blocking days increased eleven times in April 2020 relative to the climatological average, and an easterly (westerly) anomaly was observed over Mongolia-northeastern China (northern Russia). The strong blocking and EAWR pattern led to the robust atmospheric dipole structure with a prevailing northerly flow in April 2020, thereby causing the extreme cold condition over northeastern Asia. Our results provide novel insights into the cause of extreme cold condition in April over northeastern Asia.

Efficacy and safety of transarterial bleomycin sclerotherapy of early-stage facial arteriovenous malformation: Single-center multidisciplinary team experience.

BACKGROUND: To evaluate the efficacy and safety of transarterial bleomycin sclerotherapy of early-stage facial arteriovenous malformation (AVM). METHODS: A retrospective review was performed of patients who underwent bleomycin sclerotherapy for early-stage AVM (Schobinger stage I or II) in a single-referral vascular anomalies center. Bleomycin was slowly infused transarterially with flow control techniques to prolong the effects of bleomycin. Procedure details, AVM characteristics, and previous treatments were reviewed. Initial therapeutic outcomes were determined by 5 categories using both radiological and clinical findings in a 6-month follow-up. Further follow-up outcomes were reviewed to evaluate the long-term efficacy and safety of the treatment. Procedure-related complications were also analyzed. RESULTS: Nineteen patients (mean age 22.4 ± 14.0 years, 14 females) with 31 sessions of sclerotherapies were enrolled. All AVMs were Cho-Do classification type III (type IIIa [n = 13], type IIIb [n = 2], and type IIIa+b [n = 4]). Patients received a mean of 1.6 (range, 1-4) sessions of treatment. The mean cumulative bleomycin dose was 23,600 IU ± 14,500 (range, 8000 - 60,000 IU). The results showed that 14 patients (74%) were responsive to transarterial bleomycin sclerotherapy, including complete response (n = 3), marked improvement (n = 1), and partial improvement (n = 10). The remaining 5 (26%) showed no response. During a mean follow-up of 32.6 months, 5 (26%) showed slight progression compared with 6-month outcomes and 14 (74%) were stable. There were only 2 minor complications [hyperpigmentation (n = 1) and cellulitis (n = 1)]. CONCLUSIONS: Transarterial bleomycin sclerotherapy using flow control techniques can be a safe and feasible alternative treatment option for facial early-stage AVM.

Impairment of Neuronal Mitochondrial Quality Control in Prion-Induced Neurodegeneration.

Mitochondrial dynamics continually maintain cell survival and bioenergetics through mitochondrial quality control processes (fission, fusion, and mitophagy). Aberrant mitochondrial quality control has been implicated in the pathogenic mechanism of various human diseases, including cancer, cardiac dysfunction, and neurological disorders, such as Alzheimer's disease, Parkinson's disease, and prion disease. However, the mitochondrial dysfunction-mediated neuropathological mechanisms in prion disease are still uncertain. Here, we used both in vitro and in vivo scrapie-infected models to investigate the involvement of mitochondrial quality control in prion pathogenesis. We found that scrapie infection led to the induction of mitochondrial reactive oxygen species (mtROS) and the loss of mitochondrial membrane potential (ΔΨm), resulting in enhanced phosphorylation of dynamin-related protein 1 (Drp1) at Ser616 and its subsequent translocation to the mitochondria, which was followed by excessive mitophagy. We also confirmed decreased expression levels of mitochondrial oxidative phosphorylation (OXPHOS) complexes and reduced ATP production by scrapie infection. In addition, scrapie-infection-induced aberrant mitochondrial fission and mitophagy led to increased apoptotic signaling, as evidenced by caspase 3 activation and poly (ADP-ribose) polymerase cleavage. These results suggest that scrapie infection induced mitochondrial dysfunction via impaired mitochondrial quality control processes followed by neuronal cell death, which may have an important role in the neuropathogenesis of prion diseases.

Cellular Prion Protein Is Closely Associated with Early Recurrence and Poor Survival in Patients with Hepatocellular Carcinoma.

The cellular prion protein (PrPC) is known to play a role in cancer proliferation and metastasis. However, the role of PrPC expression in hepatocellular carcinoma (HCC) is unknown. This study investigated whether overexpression of PrPC affects recurrence after surgical resection and survival in HCC. A total of 110 HCC patients who underwent hepatic resection were included. They were followed up for a median of 42 months (range 1-213 months) after hepatectomy. The relationships between PrPC expression and the HCC histologic features, recurrence of HCC following surgical resection, and survival of the patients were examined. Seventy-one cases (64.5%) of HCC demonstrated higher expression of PrPC. The expression of PrPC was only correlated with diabetes mellitus. There was no association between PrPC expression and age, sex, hypertension, hepatitis B virus positivity, alcohol consumption, Child-Pugh class, major portal vein invasion, serum alpha-fetoprotein, and HCC size or number. The 1-year recurrence rates in patients with higher PrPC expression were higher than those with lower PrPC expression. The cumulative survival rates of patients with higher PrPC expression were significantly shorter than those of patients with lower PrPC expression. In conclusion, PrPC expression is closely associated with early recurrence and poor survival of HCC patients following surgical resection.

Influence of cerebral microbleeds on mechanical thrombectomy outcomes.

In ischemic stroke patients undergoing endovascular treatment (EVT), we aimed to test the hypothesis that cerebral microbleeds (CMBs) are associated with clinical outcomes, while estimating the mediating effects of hemorrhagic transformation (HT), small-vessel disease burden (white matter hyperintensities, WMH), and procedural success. From a multicenter EVT registry, patients who underwent pretreatment MR imaging were analyzed. They were trichotomized according to presence of CMBs (none vs. 1-4 vs. ≥ 5). The association between CMB burden and 3-month mRS was evaluated using multivariable ordinal logistic regression, and mediation analyses were conducted to estimate percent mediation. Of 577 patients, CMBs were present in 91 (15.8%); 67 (11.6%) had 1-4 CMBs, and 24 (4.2%) had ≥ 5. Increases in CMBs were associated with hemorrhagic complications (ß = 0.27 [0.06-0.047], p = 0.010) in multivariable analysis. The CMB effect on outcome was partially mediated by post-procedural HT degree (percent mediation, 14% [0-42]), WMH (23% [7-57]) and lower rates of successful reperfusion (6% [0-25]). In conclusion, the influence of CMBs on clinical outcomes is mediated by small-vessel disease burden, post-procedural HT, and lower reperfusion rates, listed in order of percent mediation size.

Intracranial non-occlusive intraluminal thrombus may indicate underlying etiology of large vessel occlusion in patients undergoing endovascular therapy.

BACKGROUND: The underlying etiology of intracranial non-occlusive intraluminal thrombus (iNOT) remains unknown. This study aimed to investigate whether the presence of iNOT can indicate the underlying etiology of large vessel occlusion (LVO) in patients undergoing endovascular therapy (EVT). METHODS: Among patients who underwent EVT at three comprehensive stroke centers, we included those with intracranial LVO in the anterior circulation. The presence of iNOT was determined by pretreatment DSA. We investigated the association between iNOT and intracranial atherosclerotic stenosis (ICAS) related LVO. RESULTS: Of 546 patients, 44 (8.1%) had iNOT. Patients with iNOT were younger, had less hypertension, atrial fibrillation, and a history of antiplatelet use. In addition, the involvement of the M1 segment of the middle cerebral artery (MCA) was more frequent. However, they had a lower National Institutes of Health Stroke Scale (NIHSS) score on admission and longer onset to recanalization time compared with patients with no iNOT. In a logistic regression model adjusting for age, sex, atrial fibrillation, smoking, prior antiplatelet and anticoagulant use, intravenous tissue plasminogen activator, NIHSS on admission, number of technical trials, intraprocedural re-occlusion, and the location of LVO (p<0.10 in the univariate analysis), the presence of iNOT was significantly associated with ICAS related LVO (adjusted OR 3.04; 95% CI 1.33 to 6.90; p=0.007). CONCLUSIONS: The presence of iNOT may reflect an underlying ICAS related LVO in patients undergoing EVT.

Multiple functions of pyruvate kinase M2 in various cell types.

Glucose metabolism is a mechanism by which energy is produced in form of adenosine triphosphate (ATP) by mitochondria and precursor metabolites are supplied to enable the ultimate enrichment of mature metabolites in the cell. Recently, glycolytic enzymes have been shown to have unconventional but important functions. Among these enzymes, pyruvate kinase M2 (PKM2) plays several roles including having conventional metabolic enzyme activity, and also being a transcriptional regulator and a protein kinase. Compared with the closely related PKM1, PKM2 is highly expressed in cancer cells and embryos, whereas PKM1 is dominant in mature, differentiated cells. Posttranslational modifications such as phosphorylation and acetylation of PKM2 change its cellular functions. In particular, PKM2 can translocate to the nucleus, where it regulates the transcription of many target genes. It is notable that PKM2 also acts as a protein kinase to phosphorylate several substrate proteins. Besides cancer cells and embryonic cells, astrocytes also highly express PKM2, which is crucial for lactate production via expression of lactate dehydrogenase A (LDHA), while mature neurons predominantly express PKM1. The lactate produced in cancer cells promotes tumor progress and that in astrocytes can be supplied to neurons and may act as a major source for neuronal ATP energy production. Thereby, we propose that PKM2 along with its different posttranslational modifications has specific purposes for a variety of cell types, performing unique functions.

Retrospective 6 month-outcomes and prognostic factors following spontaneous angiogram-negative non-perimesencephalic subarachnoid hemorrhage.

Our objective was to analyze functional outcomes and prognostic factors in patients suffering from angiogram-negative non-perimesencephalic subarachnoid hemorrhage (non-PMH). In total, 1601 patients presenting with spontaneous SAH between January 2009 to December 2019 admitted to our institution were reviewed. Among them, 51 patients with angiogram negative non-perimesencephalic subarachnoid hemorrhage were analyzed. We divided patients into groups according to hemorrhage pattern and duration. Prognostic factors were assessed according to initial neurologic grade, early hydrocephalus, fisher grade, and duration of hemorrhage. Outcomes were assessed according to the modified Rankin Scale after 6 months. Overall, 41 patients (80.3%) with angiogram-negative non-PMH achieved a favorable outcome. In univariate analysis, good initial neurologic grade, absence of early hydrocephalus, non-Fisher-type 3 bleeding pattern, and short term hemorrhage (blood wash out <7 days after onset) duration were significantly associated with a favorable outcome. In multivariate analysis, a non-Fisher-type 3 hemorrhagic pattern (p < 0.05) and good initial neurologic state (p < 0.01) were independent predictors of favorable outcomes in angiogram-negative non-PMH patients. Patients with angiogram-negative non-PMH generally had favorable outcomes. A non-Fisher-type 3 hemorrhagic pattern and good initial neurologic state were prognostic factors of a favorable outcome in non-PMH. Furthermore, patients with long-term SAH were more likely to develop hydrocephalus. Evaluating the pattern and duration of subarachnoid hemorrhage may allow better prediction of outcomes in patients with angiogram negative and non-PMH.

Impact of Left Atrial Appendage Morphology on Recurrence in Embolic Stroke of Undetermined Source and Atrial Cardiopathy.

Background: The left atrial appendage (LAA) is a major source of thrombus and non-chicken wing (CW). LAA morphology is a risk factor for embolic events in atrial fibrillation. However, the association of non-CW morphology with embolic stroke recurrence is unknown in patients with embolic stroke of undetermined source (ESUS) and atrial cardiopathy. Methods: We conducted retrospective analyses using a prospective institutional stroke registry (2013-2017). Patients with ESUS and atrial cardiopathy were enrolled. Atrial cardiopathy was diagnosed if an increased left atrial diameter (>40 mm, men; >38 mm, women), supraventricular tachycardia, or LAA filling defect on computed tomography (CT) were present. Patients admitted >24 h after onset were excluded. LAA morphology was evaluated using CT and categorized into CW vs. non-CW types. The primary outcome was embolic stroke recurrence. Multivariable Cox proportional hazards models were used to examine the independent association between LAA morphology and outcome. Results: Of 157 patients, 81 (51.6%) had CW LAA morphology. The median follow-up was 41.5 (interquartile range 12.3-58.5) months corresponding to 509.8 patient years. In total, 18 participants experienced embolic stroke recurrences (3.80 per 100 patient-years). Non-CW morphology was more associated with embolic stroke recurrence than CW morphology (hazard ratio (HR), 3.17; 95% confidence interval (CI), 1.13-8.91; p = 0.029). After adjusting for CHA2DS2-VASc score and number of potential embolic sources, non-CW morphology showed an independent association with outcome (adjusted HR, 2.90; 95% CI, 1.02-8.23; p = 0.045). Conclusions: The LAA morphology types may help identify high risk of embolic stroke recurrence in ESUS with atrial cardiopathy. LAA morphology in atrial cardiopathy may provide clues for developing therapies tailored to specific mechanisms.

Preparation and Characterization of Carbon Fibers from Lyocell Precursors Grafted with Polyacrylamide via Electron-Beam Irradiation.

Carbon fibers, which act as reinforcements in many applications, are often obtained from polyacrylonitrile (PAN). However, their production is expensive and results in waste problems. Therefore, we focused on producing carbon fibers from lyocell, a cellulose-based material, and analyzed the effects of the process parameters on their mechanical properties and carbon yields. Lyocell was initially grafted with polyacrylamide (PAM) via electron-beam irradiation (EBI) and was subsequently stabilized and carbonized. Thermal analysis showed that PAM grafting increased the carbon yields to 20% at 1000 °C when compared to that of raw lyocell, which degraded completely at about 600 °C. Stabilization further increased this yield to 55%. The morphology of the produced carbon fibers was highly dependent on PAM concentration, with fibers obtained at concentrations ≤0.5 wt.% exhibiting clear, rigid, and round cross-sections with smooth surfaces, whereas fibers obtained from 2 and 4 wt.% showed peeling surfaces and attachment between individual fibers due to high viscosity of PAM. These features affected the mechanical properties of the fibers. In this study, carbon fibers of the highest tensile strength (1.39 GPa) were produced with 0.5 wt.% PAM, thereby establishing the feasibility of using EBI-induced PAM grafting on lyocell fabrics to produce high-performance carbon fibers with good yields.

Involvement of Cellular Prion Protein in Invasion and Metastasis of Lung Cancer by Inducing Treg Cell Development.

The cellular prion protein (PrPC) is a cell surface glycoprotein expressed in many cell types that plays an important role in normal cellular processes. However, an increase in PrPC expression has been associated with a variety of human cancers, where it may be involved in resistance to the proliferation and metastasis of cancer cells. PrP-deficient (Prnp0/0) and PrP-overexpressing (Tga20) mice were studied to evaluate the role of PrPC in the invasion and metastasis of cancer. Tga20 mice, with increased PrPC, died more quickly from lung cancer than did the Prnp0/0 mice, and this effect was associated with increased transforming growth factor-beta (TGF-ß) and programmed death ligand-1 (PD-L1), which are important for the development and function of regulatory T (Treg) cells. The number of FoxP3+CD25+ Treg cells was increased in Tga20 mice compared to Prnp0/0 mice, but there was no significant difference in either natural killer or cytotoxic T cell numbers. In addition, mice infected with the ME7 scrapie strain had decreased numbers of Treg cells and decreased expression of TGF-ß and PD-L1. These results suggest that PrPC plays an important role in invasion and metastasis of cancer cells by inducing Treg cells through upregulation of TGF-ß and PD-L1 expression.

Prominent hypointense vessel on susceptibility-weighted images accompanying hyperacute and acute large infarction.

BACKGROUND: Multiple prominent hypointense vessels on susceptibility-weighted image (SWI) have been found in the ischemic territory of patients with acute ischemic stroke. SWI is suitable for venous imaging. PURPOSE: To evaluate the conditions of prominent hypointense vessel (PHV) in hyperacute and acute cerebral infarctions using susceptibility-weighted image (SWI). MATERIALS AND METHODS: Magnetic resonance images, including SWI, of 284 patients with acute infarction were evaluated. Based on lesion size, the infarction was classified as a small (< 3 cm) or a large (> 3 cm) infarction. Stage of infarction was classified as hyperacute (< 6 h) or acute (> 6 h, < 1 week) on the basis of the onset of stroke. The site of infarction was categorised as a deep grey matter or a mixed (cortical and/or deep grey matter) infarction. The venous structures were analysed qualitatively for the calibre difference between ipsilateral and contralateral hemispheres. We quantitatively analysed the relationship between the size of areas with PHV on SWI and the abnormalities on MR angiography, apparent diffusion coefficient value, and signal intensity on T2WI in the 271 patients. RESULTS: PHV over the infarction site was observed in 54.1% (137/253) of the large infarctions, and 19.3% (6/31) of the small infarctions on SWI. PHV was demonstrated in 63.1% (118/187) of mixed infarctions and 25.8% (25/97) of deep grey matter infarctions, and 59.2% (58/98) in hyperacute and 45.7% (85/186) of acute infarctions. The presence of PHV was statistically significant in the size and region of cerebral infarction (p < 0.05), and was not significant in the stage of infarction (p = 0.137). Quantitative analysis revealed significant differences in the MRA abnormalities and ADC values in the PHV ( +) group (p < 0.05) and no significant difference in the T2WI SI ratio in the PHV ( +) group (p = 0.086), compared with PHV (-) group. CONCLUSION: PHV on SWI was more prominent at the portions with the large and mixed infarctions. PHV was observed both in hyperacute and acute infarction.

Usefulness of combination usage of balloon guide catheter with contact aspiration thrombectomy.

BACKGROUND: Angiographic outcomes of contact aspiration thrombectomy (CAT), a frontline thrombectomy strategy, can vary depending on balloon guide catheter (BGC) usage, stroke etiology, and occlusion location. The purpose of this study was to analyze conditional outcomes of CAT to determine which result in maximum angiographic benefits. METHODS: Patients who received CAT for anterior circulation occlusive stroke between January 2017 and December 2018 were included. Angiographic and clinical outcomes were compared relative to BGC use, stroke etiology, and occlusion location. Multivariable analyses for first-pass reperfusion (FPR) and favorable clinical outcome were performed. RESULTS: Of 160 included patients, the rates of FPR, successful reperfusion after CAT, final successful reperfusion, and favorable clinical outcome were 43.1%, 58.1%, 81.9%, and 60.6%, respectively. BGC use was associated with a higher rate of FPR, successful reperfusion after CAT, a lower rate of distal embolization, and faster reperfusion. Based on subgroup analysis, BGC usage in ICA, MCA M1 occlusion, and cardioembolism were associated with higher FPR, successful reperfusion after CAT, and lower distal embolization. Faster reperfusion was achieved in ICA occlusions and cardioembolisms. BGC usage was an independent predictor of FPR. Favorable clinical outcome was associated with male gender, low initial NIHSS score, fast onset to reperfusion, and FPR. CONCLUSIONS: In CAT, BGC usage was associated with better angiographic outcomes, including higher FPR, successful reperfusion after CAT, prevention of distal embolization, and faster reperfusion, especially in proximal occlusions and cardioembolisms. These conditions may play a role in maximizing the benefits of CAT.

Establishment of Method for the Determination of Aggregated α-Synuclein in DLB Patient Using RT-QuIC Assay.

BACKGROUND: The accumulation of aggregated α-synuclein (αSyn) is known as one of the critical reasons to exhibit their variable molecular pathologies and phenotypes in synucleinopathies. Recent studies suggested that the real-time quaking-induced conversion (RT-QuIC) assay is one of the potential methods to detect these αSyn aggregates and could detect the aggregated αSyn in the brain tissue and cerebrospinal fluid (CSF) using the propensity of the prion-like oligomerization. OBJECTIVE: We tried to optimize the αSyn RT-QuIC assay based on the aggregation of αSyn in brain samples of synucleinopathies by comparing the conditions of the recently reported αSyn RTQuIC assays. METHODS: This study applied a highly sensitive RT-QuIC assay using recombinant αSyn (rαSyn) to detect aggregated αSyn in the brain tissue from dementia with Lewy bodies (DLB). RESULTS: This study compared αSyn RT-QuIC assays under conditions such as beads, rαSyn as a substrate, reaction buffers, and fluorescence detectors. We observed that the addition of beads and the use of 6x His-tagged rαSyn as a substrate help to obtain higher positive responses from αSyn RT-QuIC assay seeding with brain homogenate (BH) of DLB and phosphate buffer-based reaction showed higher positive responses than HEPES buffer-based reaction on both fluorescent microplate readers. We also observed that the DLB BHs gave positive responses within 15-25h, which is faster high positive responses than recently reported assays. CONCLUSION: This established αSyn RT-QuIC assay will be able to apply to the early clinical diagnosis of αSyn aggregates-related diseases in various biofluids such as CSF.

Predictors and prognoses of Willisian collateral failure during mechanical thrombectomy.

During mechanical thrombectomy in the anterior cerebral circulation, thrombus embolization resulting in Willisian collateral failure may lead to critical stroke outcomes due to a shutdown of leptomeningeal collaterals. We hypothesized that the outcomes of dynamic Willisian collateral failure (DWF), induced during mechanical thrombectomy, would be associated with grave outcomes. We evaluated this hypothesis in consecutive patients, between January 2011 and May 2016, who underwent mechanical thrombectomy for anterior circulation occlusions, with an onset-to-puncture of 24 h. Patients with initial Willisian collateral failure (IWF) were identified first, with remaining patients classified into the DWF and Willisian collateral sparing (WCS) groups. Comparative and multivariable analyses were performed to predict grave outcomes (3-month modified Rankin Scale score of 5-6). Among 567 patients, 37 were in the IWF group, 38 in the DWF group, and 492 in the WCS group. Compared to the WCS and DWF groups, the IWF group had a higher baseline National Institute of Health Stroke Scale score and lower Alberta Stroke Program Early CT Score. The prevalence of grave outcomes was similarly high in the IWF (48.6%) and DWF (47.4%) groups, but lower in the WCS group (22.0%; p < 0.001). IWF and DWF were independent risk factors for a grave outcome.

Characterization of Activated Carbon Paper Electrodes Prepared by Rice Husk-Isolated Cellulose Fibers for Supercapacitor Applications.

For the preparation of activated carbon papers (APCs) as supercapacitor electrodes, impurity substances were removed from rice husks, before carbonization and various activation temperature treatments, to optimize electro chemical efficiency. The porosities and electrochemical performances of the ACPs depended strongly on activation temperature: The specific surface area increased from 202.92 (500 °C) to 2158.48 m2 g-1 (1100 °C). XRD and Raman analyses revealed that ACP graphitization also increased with the activation temperature. For activation at 1100 °C, the maximum specific capacitance was 255 F g-1, and over 92% of its capacitance was retained after 2000 cycles.