Background Despite remarkable advancements in intra-arterial mechanical thrombectomy (IAT), recanalization failure rates up to 24% have been reported. Recently, permanent stent placement (rescue ...stent, RS) during IAT has been suggested as an optional modality for better reperfusion and outcomes in these patients. However, previous studies were limited owing to non-standardized procedure protocols and small sample sizes. Here, we aimed to determine the efficacy and safety of RS in patients with acute ischemic stroke (AIS) with middle cerebral artery (MCA) occlusion. Methods Of the 243 patients in our IAT database (2015–2021), 183 were identified as having MCA occlusion alone. Among them, we extracted 53 patients in whom the IAT failed to show thrombolysis in cerebral ischemia (TICI) scores of 2A or worse. Intraoperatively, RS was deployed in 22 patients (RS group), whereas 31 patients (no-stent group) received IAT without stenting. The baseline characteristics and radiologic and clinical outcomes were reviewed. Comparisons between the groups and multivariate logistic analyses for recanalization and good functional outcomes (modified Rankin Scale 0–2) were performed. Results No baseline differences were noted (RS vs. no-stent); however, the recanalization outcomes (59.1% vs. 25.8%, p = 0.15) and proportion of good modified Rankin Scale scores (45.5% vs. 19.4%, p = 0.041) were better in the RS group. The parameters of symptomatic ICH (9.7% vs. 9.4%) and mortality (6.5% vs. 5.7%) showed no significant difference. In the multivariate analyses, ‘hypertension’ and ‘RS deployment’ were identified as significantly associated factors with recanalization and good prognosis. Conclusion In select patients with MCA occlusion AIS after failed IAT, the RS technique can be an optional rescue treatment modality for acquiring better functional outcomes and delayed recanalization.
Copy number variants (CNVs) account for the majority of human genomic diversity in terms of base coverage. Here, we have developed and applied a new method to combine high-resolution array ...comparative genomic hybridization (CGH) data with whole-genome DNA sequencing data to obtain a comprehensive catalog of common CNVs in Asian individuals. The genomes of 30 individuals from three Asian populations (Korean, Chinese and Japanese) were interrogated with an ultra-high-resolution array CGH platform containing 24 million probes. Whole-genome sequencing data from a reference genome (NA10851, with 28.3× coverage) and two Asian genomes (AK1, with 27.8× coverage and AK2, with 32.0× coverage) were used to transform the relative copy number information obtained from array CGH experiments into absolute copy number values. We discovered 5,177 CNVs, of which 3,547 were putative Asian-specific CNVs. These common CNVs in Asian populations will be a useful resource for subsequent genetic studies in these populations, and the new method of calling absolute CNVs will be essential for applying CNV data to personalized medicine.
Introduction
Hemodynamics of left atrial appendage (LAA) is an important factor for future risk of ischemic stroke in atrial fibrillation (AF) patients. Velocity encoded cardiac magnetic resonance ...imaging (VENC‐MRI) can evaluate blood flow volume of LAA without any invasive procedures. We aimed to evaluate the association between radiofrequency catheter ablation (RFCA) and LAA hemodynamics measured by MRI.
Methods and Results
Consecutive RFCA cases in a single arrhythmia center were retrospectively analyzed. A total of 3120 AF patients who underwent first RFCA were analyzed. Among these patients 360 patients had both pre‐ and post‐RFCA VENC‐MRI evaluation. Atrial fibrillation was non‐paroxysmal in 174 (48.3%) patients. Mean VENC‐MRI (ml/sec) was significantly improved after RFCA with 49.93 ± 32.92 and 72.00 ± 34.82 for pre‐ and post‐RFCA, respectively. Patients with non‐paroxysmal AF (∆VENC‐MRI = 14.63 ± 40.67 vs. 30.03 ± 35.37; p < .001) and low pre‐RFCA VENC‐MRI (∆VENC‐MRI = 17.19 ± 38.35 vs. 50.35 ± 29.12; p < .001) had significantly higher improvement in VENC‐MRI. Those who experienced late recurrence before post‐RFCA MRI had significantly less improvement in LAA flow volume (∆VENC‐MRI = 15.55 ± 41.41 vs. 26.18 ± 36.77; p = .011). Late recurrence and pre‐RFCA VENC‐MRI were significantly associated with ∆VENC‐MRI after adjusting covariates. Patients who were AF before RFCA but maintained sinus rhythm after RFCA showed greatest improvement in VENC‐MRI.
Conclusion
Effective rhythm control through RFCA can be associated with significant improvement in LAA hemodynamics. Low pre‐RFCA VENC‐MRI and absence of late recurrence were associated with greater improvement in LAA hemodynamics.
Aberrant nucleocytoplasmic localization of proteins has been implicated in many neurodegenerative diseases. Evidence suggests that cytoplasmic mislocalization of nuclear proteins such as transactive ...response DNA-binding protein 43 (TDP-43) and fused in sarcoma (FUS) may be associated with neurotoxicity in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. This study investigated the changes in nucleocytoplasmic distributions of the proteome and transcriptome in an in vitro model of ALS. After subcellular fractionation of motor neuron-like cell lines expressing wild-type or G93A mutant hSOD1, quantitative mass spectrometry and next-generation RNA sequencing (RNA-seq) were performed for the nuclear and cytoplasmic compartments. A subset of the results was validated via immunoblotting. A total of 1,925 proteins were identified in either the nuclear or cytoplasmic fractions, and 32% of these proteins were quantified in both fractions. The nucleocytoplasmic distribution of 37 proteins was significantly changed in mutant cells with nuclear and cytoplasmic shifts in 13 and 24 proteins, respectively (p<0.05). The proteins shifted towards the nucleus were enriched regarding pathways of RNA transport and processing (Dhx9, Fmr1, Srsf3, Srsf6, Tra2b), whereas protein folding (Cct5, Cct7, Cct8), aminoacyl-tRNA biosynthesis (Farsb, Nars, Txnrd1), synaptic vesicle cycle (Cltc, Nsf), Wnt signalling (Cltc, Plcb3, Plec, Psmd3, Ruvbl1) and Hippo signalling (Camk2d, Plcb3, Ruvbl1) pathways were over-represented in the proteins shifted to the cytoplasm. A weak correlation between the changes in protein and mRNA levels was found only in the nucleus, where mRNA was relatively abundant in mutant cells. This study provides a comprehensive dataset of the nucleocytoplasmic distribution of the proteome and transcriptome in an in vitro model of ALS. An integrated analysis of the nucleocytoplasmic distribution of the proteome and transcriptome demonstrated multiple candidate pathways including RNA processing/transport and protein synthesis and folding that may be relevant to the pathomechanism of ALS.
Abstract
Sudden cardiac arrest (SCA) is a medical disaster for both the victim and the society. Despite intrinsic limitations in the management of SCA, primary prevention has been overlooked and risk ...factors for SCA are not fully understood. We aimed to evaluate whether hypertension and diabetes mellitus (DM), including pre-hypertension and impaired fasting glucose (IFG), are associated with increased risk of SCA. We performed a nationwide population-based analysis using the Korean National Health Insurance Service. People who underwent a national health check-up in 2009 were enrolled. The risk of SCA was evaluated in people with hypertension and DM with a clinical follow-up through December 2018. A total of 4,056,423 people with 33,345,378 person-years of follow-up and 16,352 SCA events were examined. People with hypertension had 65.4% increased risk of SCA (adjusted hazard ratio HR = 1.654 1.572–1.739; p < 0.001). Pre-hypertension was also associated with 21.3% increased risk of SCA (adjusted HR = 1.213 1.158–1.272; p < 0.001). People who had IFG and DM showed 7.5% (adjusted HR = 1.075 1.035–1.117; p < 0.001) and 80.1% (adjusted HR = 1.801 1.731–1.875; p < 0.001) increased risk of SCA, respectively. People with DM who took anti-diabetic medication showed significantly lower risk of SCA compared with uncontrolled DM patients (fasting glucose ≥ 200 mg/dL) (adjusted HR = 0.625 0.533–0.733; p < 0.001). Coexistence of hypertension and DM was associated with an even higher risk of SCA (adjusted HR = 3.078 2.877–3.293; p < 0.001). In conclusion, the risk of SCA is significantly higher in people with hypertension and DM, including pre-hypertension and IFG. Adequate control of blood pressure and serum glucose can have a profound impact for the primary prevention of SCA in the general population.
•A cost-effective and rapid method for manufacturing cutting tools is investigated.•Samples obtained from slurry cast exhibit adequate hardness and fracture toughness.•Results validate the ...manufacture of cutting tools without expensive metal molds.•Complex shapes can be implemented precisely in development stage via 3D printing.
Tungsten carbide-Cobalt (WC-Co), also known as cemented carbide, is a widely used alloy to manufacture high-performance tools for mining, drilling, cutting, and machining applications. Due to the high melting point of WC, it is challenging to cast it to manufacture products. Therefore, in this study, we investigated a method for manufacturing cutting tools from WC-Co alloy using high-precision digital light processing-based three-dimensional (3D) printing technology. The high refractive index of WC renders it difficult to directly apply it to photocurable 3D printing. Therefore, a polymer mold was fabricated via 3D printing to obtain a WC-Co slurry cast. Rheological studies were performed to optimize the slurry composition. After slurry casting and drying, a green body was formed, which was sintered at 1400 °C to obtain a defect-free sample with a shape identical to that of the 3D model. The cast sample exhibited identical characteristics (microstructure, hardness, and fracture toughness) to those of conventional press-molded sample. The results of this study confirm that complex cutting tool manufacturing is possible without using expensive metal molds. The presented approach is expected to significantly reduce the cost and time incurred during the product development stage involving multiple designs.
•CS nanofiber mat with enlarged porosity and thickness achieved using sonication.•The BCI value for the sonicated CS nanofiber mat was lower than for other samples.•Sonicated CS nanofiber mats had ...decreased water absorption time and contact angle.•Cell viability on the sonicated mat was higher than non-sonicated mat.
Electrospinning of pure chitosan was employed to obtain a nanofibrous hemostatic material. Owing to the water-solubility of the resulting acidic chitosan nanofibers, the optimum neutralization conditions were identified by testing various alkaline solutions, so that an insoluble material could be achieved. The pore size and thickness of the neutralized chitosan nanofibers mat could be controlled using ultra-sonication. The porosity of the chitosan mat was increased from 79.9% to 97.2% with ultra-sonication treatment for 1min, and the water absorption time decreased from 110s to 9s. The blood clotting efficiency measured for the sonicated chitosan nanofiber mat was 1.35- and 3.41-fold better than the efficiencies of the Surgicel® and chitosan sponge, respectively. In addition, the proliferation of normal human dermal fibroblasts on the sonicated nanofiber mat was found to be 1.4-fold higher than that on the non-sonicated material after 7 days of culture.
► Degradation of laminarin by gamma radiation. ► Decrease in molecular weight by random scission of glycosidic bond. ► Formation of carbonyl groups and increase in antioxidant property.
Recently, it ...has been reported that low molecular weight laminarin had enhanced biological activities. In this study, laminarin was degraded by gamma irradiation, and the changes in its structure and antioxidant property were investigated. Gel permeation chromatography data showed that the average molecular weight of the irradiated laminarin decreased significantly as the irradiation dose increased. The absorbance at 290nm, from UV spectra, was increased, depending on the irradiation dose and caused by the formation of carbonyl groups. From the NMR analysis, the ratio of β-1,3- to β-1,6-linkages was not changed, indicating the random scission of chains by gamma irradiation. The antioxidative activities, measured by Rancimat test, were all increased in the gamma-irradiated laminarin, depending on the absorbed dose, presumably due to the carbonyl groups formed by gamma irradiation. Therefore, gamma irradiation could be a promising method for preparing low molecular weight laminarin with enhanced biological activities.
Vertical sleeve gastrectomy (VSG) is the most commonly performed bariatric/metabolic surgery, exhibiting a high rate of diabetes remission in humans. To elucidate the molecular mechanisms of VSG, we ...performed transcriptomic analysis of the liver, fat, and muscle in VSG mice. C57BL/6 mice fed a high-fat diet were randomly assigned to sham or VSG surgery. The sham-operated mice were fed ad libitum (sham group) or pair-fed (sham-PF group) matching their food intake to the VSG-operated mice. Comparative transcriptomic analysis of the liver, fat, and muscle using RNA sequencing was performed. VSG reduced body weight and improved glucose tolerance compared to the sham group, but not more than the sham-PF group. Improvement in fatty liver and adipose tissue inflammation was comparable between VSG and sham-PF. However, global gene expression profiles showed distinctive changes in the liver, fat, and muscle of the VSG group compared to both the sham or sham-PF groups. The liver showed the most prominent gene expression changes. Immune response-related pathways were commonly upregulated in the three organs of the VSG group compared to the sham or sham-PF. VSG induces organ-specific gene expression changes in the liver, fat, and muscle, which may play critical roles in metabolic improvements after VSG.
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