Comparison of Clinical Effectiveness and Safety of Drug-Coated Balloons versus Percutaneous Transluminal Angioplasty in Arteriovenous Fistulae: A Review of Systematic Reviews and Updated Meta-Analysis.

PURPOSE: To evaluate the clinical effectiveness and safety of drug-coated balloons (DCBs) compared with those of percutaneous transluminal angioplasty (PTA) for arteriovenous fistula (AVF) stenosis via a review of systematic reviews (SRs) and an update of the current meta-analysis. MATERIALS AND METHODS: Literature was searched to retrieve SRs comparing DCBs and PTA for AVFs. A narrative review of SRs and pooled analysis were performed. RESULTS: Eleven SRs were included. DCBs demonstrated favorable outcomes at 6 and 12 months compared with PTA, with improved patency in 7 SRs and a trend toward favorable outcomes without statistical significance in 3 SRs. Target lesion revascularization (TLR) was reported in 3 SRs; 2 reviews reported a significantly lower incidence in the DCB group than in the PTA group, whereas 1 review reported no significant differences at 12 months. Four studies reporting all-cause mortality revealed no significant difference between the 2 treatments. In the updated meta-analysis including 23 studies, DCBs demonstrated improved primary patency at 6 months (risk ratio [RR], 1.27; 95% CI, 1.07-1.50) and 12 months (RR, 1.36; 95% CI, 1.19-1.55) and were associated with a lower incidence of TLR at 6 months (RR, 0.54; 95% CI, 0.41-0.73) and 12 months (RR, 0.78; 95% CI, 0.62-0.99). There was no difference in mortality between the 2 groups for 24 months. CONCLUSIONS: A review of SRs and meta-analysis update revealed the consistent benefits of DCBs over PTA in treating AVFs in terms of primary patency and TLR. Compared with PTA, DCBs do not increase mortality risk.

Comparison of Metabarcoding and Microscopy Methodologies to Analyze Diatom Communities in Five Estuaries Along the Southern Coast of the Korean Peninsula.

The study of microalgal communities is critical for understanding aquatic ecosystems. These communities primarily comprise diatoms (Heterokontophyta), with two methods commonly used to study them: Microscopy and metabarcoding. However, these two methods often deliver different results; thus, their suitability for analyzing diatom communities is frequently debated and evaluated. This study used these two methods to analyze the diatom communities in identical water samples and compare the results. The taxonomy of the species constituting the diatom communities was confirmed, and both methods showed that species belonging to the orders Bacillariales and Naviculales (class Bacillariophyceae) are the most diverse. In the lower taxonomic levels (family, genus, and species), microscopy tended to show a bias toward detecting diatom species (Nitzschia frustulum, Nitzschia inconspicua, Nitzschia intermedia, Navicula gregaria, Navicula perminuta, Navicula recens, Navicula sp.) belonging to the Bacillariaceae and Naviculaceae families. The results of the two methods differed in identifying diatom species in the communities and analyzing their structural characteristics. These results are consistent with the fact that diatoms belonging to the genera Nitzschia and Navicula are abundant in the communities; furthermore, only the Illumina MiSeq data showed the abundance of the Melosira and Entomoneis genera. The results obtained from microscopy were superior to those of Illumina MiSeq regarding species-level identification. Based on the results obtained via microscopy and Illumina MiSeq, it was revealed that neither method is perfect and that each has clear strengths and weaknesses. Therefore, to analyze diatom communities effectively and accurately, these two methods should be combined.

Assessment of potential ecological risk for polycyclic aromatic hydrocarbons in urban soils with high level of atmospheric particulate matter concentration.

Polycyclic aromatic hydrocarbons (PAHs) are known to be representative carcinogenic environmental pollutants with high toxicity. However, information on the potential ecological and environmental risks of PAH contamination in soil remains scarce. Thus, this study was evaluated the potential ecological risks of PAHs in soils of five Korean areas (Gunsan (GS), Gwangju, Yeongnam, Busan, and Gangwon) using organic carbon (OC)-normalized analysis, mean effect range-median quotient (M-ERM-Q), toxic equivalent quantity (TEQ) analysis, and risk quotient (RQ) derived by the species sensitivity distribution model. In this study, atmospheric particulate matter has a significant effect on soil pollution in GS through the presence of hopanes and the similar pattern of PAHs in soil and atmospheric PAHs. From analysis of source identification, combustion sources in soils of GS were important PAH sources. For PAHs in soils of GS, the OC-normalized analysis, M-ERM-Q, and TEQ analysis have 26.78 × 105 ng/g-OC, 0.218, and 49.72, respectively. Therefore, the potential ecological risk assessment results showed that GS had moderate-high ecological risk and moderate-high carcinogenic risk, whereas the other regions had low ecological risk and low-moderate carcinogenic risk. The risk level (M-ERM-Q) of PAH contamination in GS was similar to that in Changchun and Xiangxi Bay in China. The Port Harcourt City in Nigeria for PAH has the highest risk (M-ERM-Q = 4.02 and TEQ = 7923). Especially, compared to China (RQPhe =0.025 and 0.05), and Nigeria (0.059), phenanthrene showed the highest ecological risk in Korea (0.001-0.18). Korea should focus on controlling the release of PAHs originating from the PM in GS.

A Comparison of Two LDL Cholesterol Targets after Ischemic Stroke.

BACKGROUND: The use of intensive lipid-lowering therapy by means of statin medications is recommended after transient ischemic attack (TIA) and ischemic stroke of atherosclerotic origin. The target level for low-density lipoprotein (LDL) cholesterol to reduce cardiovascular events after stroke has not been well studied. METHODS: In this parallel-group trial conducted in France and South Korea, we randomly assigned patients with ischemic stroke in the previous 3 months or a TIA within the previous 15 days to a target LDL cholesterol level of less than 70 mg per deciliter (1.8 mmol per liter) (lower-target group) or to a target range of 90 mg to 110 mg per deciliter (2.3 to 2.8 mmol per liter) (higher-target group). All the patients had evidence of cerebrovascular or coronary-artery atherosclerosis and received a statin, ezetimibe, or both. The composite primary end point of major cardiovascular events included ischemic stroke, myocardial infarction, new symptoms leading to urgent coronary or carotid revascularization, or death from cardiovascular causes. RESULTS: A total of 2860 patients were enrolled and followed for a median of 3.5 years; 1430 were assigned to each LDL cholesterol target group. The mean LDL cholesterol level at baseline was 135 mg per deciliter (3.5 mmol per liter), and the mean achieved LDL cholesterol level was 65 mg per deciliter (1.7 mmol per liter) in the lower-target group and 96 mg per deciliter (2.5 mmol per liter) in the higher-target group. The trial was stopped for administrative reasons after 277 of an anticipated 385 end-point events had occurred. The composite primary end point occurred in 121 patients (8.5%) in the lower-target group and in 156 (10.9%) in the higher-target group (adjusted hazard ratio, 0.78; 95% confidence interval, 0.61 to 0.98; P = 0.04). The incidence of intracranial hemorrhage and newly diagnosed diabetes did not differ significantly between the two groups. CONCLUSIONS: After an ischemic stroke or TIA with evidence of atherosclerosis, patients who had a target LDL cholesterol level of less than 70 mg per deciliter had a lower risk of subsequent cardiovascular events than those who had a target range of 90 mg to 110 mg per deciliter. (Funded by the French Ministry of Health and others; Treat Stroke to Target ClinicalTrials.gov number, NCT01252875.).

Assessment of indoor radon exposure in South Korea.

The objective of this study is to update the national and regional indoor radon concentrations in South Korea and assess indoor radon exposure. Based on the previously published survey results and the collected measurement data of surveys conducted since 2011, a total of 9271 indoor radon measurement data covering 17 administrative divisions are finally used for analysis. The annual effective dose from the indoor radon exposure is calculated using dose coefficients recommended by the International Commission on Radiological Protection. The population-weighted average indoor radon concentration was estimated to be a geometric mean of 46 Bq m-3(GSD = 1.2) with 3.9% of all samples showing values exceeding 300 Bq m-3. The regional average indoor radon concentration ranged from 34 to 73 Bq m-3. The radon concentrations in detached houses were relatively higher than those in public buildings and multi-family houses. The annual effective doses to the Korean population due to indoor radon exposure were estimated to be 2.18 mSv. The updated values in this study might better represent the national indoor radon exposure level in South Korea because they contain more samples and cover a wider range of geographical areas than previous studies.

Evidence for Dissociation and Ionization in Shock Compressed Nitrogen to 800 GPa.

Triple bonding in the nitrogen molecule (N_{2}) is among the strongest chemical bonds with a dissociation enthalpy of 9.8 eV/molecule. Nitrogen is therefore an excellent test bed for theoretical and numerical methods aimed at understanding how bonding evolves under the influence of the extreme pressures and temperatures of the warm dense matter regime. Here, we report laser-driven shock experiments on fluid molecular nitrogen up to 800 GPa and 4.0 g/cm^{3}. Line-imaging velocimetry measurements and impedance matching method with a quartz reference yield shock equation of state data of initially precompressed nitrogen. Comparison with numerical simulations using path integral Monte Carlo and density functional theory molecular dynamics reveals clear signatures of chemical dissociation and the onset of L-shell ionization. Combining data along multiple shock Hugoniot curves starting from densities between 0.76 and 1.29 g/cm^{3}, our study documents how pressure and density affect these changes in chemical bonding and provides benchmarks for future theoretical developments in this regime, with applications for planetary interior modeling, high energy density science, and inertial confinement fusion research.

Shock growth of ice crystal near equilibrium melting pressure under dynamic compression.

Crystal growth is governed by an interplay between macroscopic driving force and microscopic interface kinetics at the crystal-liquid interface. Unlike the local equilibrium growth condition, the interplay becomes blurred under local nonequilibrium, which raises many questions about the nature of diverse crystal growth and morphological transitions. Here, we systematically control the growth condition from local equilibrium to local nonequilibrium by using an advanced dynamic diamond anvil cell (dDAC) and generate anomalously fast growth of ice VI phase with a morphological transition from three- to two-dimension (3D to 2D), which is called a shock crystal growth. Unlike expected, the shock growth occurs from the edges of 3D crystal along the (112) crystal plane rather than its corners, which implies that the fast compression yields effectively large overpressure at the crystal-liquid interface, manifesting the local nonequilibrium condition. Molecular dynamics (MD) simulation reproduces the faster growth of the (112) plane than other planes upon applying large overpressure. Moreover, the MD study reveals that the 2D shock crystal growth originates from the similarity of the interface structure between water and the (112) crystal plane under the large overpressure. This study provides insight into crystal growth under dynamic compressions, which makes a bridge for the unknown behaviors of crystal growth between under static and dynamic pressure conditions.

Graphene Nanoribbon Hybridization of Zeolitic Imidazolate Framework Membranes for Intrinsic Molecular Separation.

Zeolitic imidazolate frameworks (ZIFs) are promising for gas separation membrane, but their molecular cut-off differs from that expected from its intrinsic aperture structure because of their flexibility. Herein, we introduced graphene nanoribbons (GNRs) to rigidify the ZIF framework. Because the sp2 edge of the GNRs induces strong anchoring effects, the modified layer can be rigidified. Particularly, when the GNRs were embedded and distributed in the ZIF-8 layer, an intrinsic aperture size of 3.4 Šwas observed, resulting in high H2 /CO2 separation (H2 permeance: 5.2×10-6  mol/m2 Pa s, ideal selectivity: 142). The performance surpasses the upper bound of polycrystalline MOF membrane performance. In addition, the membrane can be applied to blue H2 production, as demonstrated with a simulated steam reformed gas containing H2 /CO2 /CH4 . The separation performance was retained in the presence of water. The fundamentals of the molecular transport through the rigid ZIF-8 framework were revealed using molecular dynamics simulations.

Atherosclerotic Burden and Vascular Risk in Stroke Patients With Atrial Fibrillation.

Background and Purpose: Data on the effect on vascular outcomes of concomitant atherosclerotic vascular disease (ASVD) with atrial fibrillation (AF) after stroke are limited. This study evaluated the effect of ASVD with AF versus AF only on the risk of vascular events. Methods: We retrospectively analyzed a prospectively registered multicenter database involving 3213 stroke patients with AF. ASVD included extracranial atherosclerosis measured in the proximal portion of the internal carotid artery, intracranial atherosclerosis (all ≥50% stenosis), coronary artery disease, and peripheral artery disease and was categorized into 4 strata depending on the number of ASVDs (0, 1, 2, and 3­4). The independent associations of ASVD with major adverse cardiovascular events, stroke, and all-cause death were assessed. Results: A total of 2670 patients were included (mean age, 73.5±9.8 years; median CHA2DS2-VASc score, 5; interquartile range, 4−6). During the follow-up (mean, 1.7 years), a total of 672 (25.2%) major adverse cardiovascular events, 170 (6.4%) stroke events, and 501 (18.8%) all-cause deaths were noted. The adjusted hazard ratio for major adverse cardiovascular events versus no ASVD was 1.25 (95% CI, 1.00­1.56) for ASVD 1, 1.34 (95% CI, 1.02­1.76) for ASVD 2, and 1.93 (95% CI, 1.24­2.99) for ASVD 3­4. The adjusted hazard ratio for all-cause death versus no ASVD was 1.32 (1.01­1.74), 1.47 (1.06­2.03), and 2.39 (1.47­3.89), respectively. Among ASVD components, the presence of symptomatic or asymptomatic extracranial atherosclerosis was a more potent predictor of major adverse cardiovascular events (1.27 [1.05­1.54]) and all-cause death (1.45 [1.17­1.81]). Conclusions: ASVD burden with AF can be a cumulative marker of a high risk for untoward vascular outcomes. Among ASVD components, extracranial atherosclerosis seems to have a predominant effect.

Pre-Admission CHADS2 and CHA2DS2-VASc Scores on Early Neurological Worsening.

BACKGROUND: Stroke risk scores (CHADS2 and CHA2DS2-VASc) not only predict the risk of stroke in atrial fibrillation (AF) patients, but have also been associated with prognosis after stroke. OBJECTIVE: The aim of this study was to evaluate the relationship between stroke risk scores and early neurological deterioration (END) in ischemic stroke patients with AF. METHODS: We included consecutive ischemic stroke patients with AF admitted between January 2013 and December 2015. CHADS2 and CHA2DS2-VASc scores were calculated using the established scoring system. END was defined as an increase ≥2 on the total National Institutes of Health Stroke Scale (NIHSS) score or ≥1 on the motor NIHSS score within the first 72 h of admission. RESULTS: A total of 2,099 ischemic stroke patients with AF were included. In multivariable analysis, CHA2DS2-VASc score (adjusted odds ratio [aOR] = 1.17, 95% confidence interval [CI] = 1.04-1.31) was significantly associated with END after adjusting for confounders. Initial NIHSS score, use of anticoagulants, and intracranial atherosclerosis (ICAS) were also found to be closely associated with END, independent of the CHA2DS2-VASc score. Multivariable analysis stratified by the presence of ICAS demonstrated that both CHA2DS2-VASc (aOR = 1.20, 95% CI = 1.04-1.38) and CHADS2 scores (aOR = 1.24, 95% CI = 1.01-1.52) were closely related to END in only patients with ICAS. In patients without ICAS, neither of the risk scores were associated with END. CONCLUSIONS: High CHA2DS2-VASc score was associated with END in ischemic stroke patients with AF. This close relationship is more pronounced in patients with ICAS.

Cilostazol Versus Aspirin in Ischemic Stroke Patients With High-Risk Cerebral Hemorrhage: Subgroup Analysis of the PICASSO Trial.

Background and Purpose- Although cilostazol has shown less hemorrhagic events than aspirin, only marginal difference was observed in hemorrhagic stroke events among patients at high risk for cerebral hemorrhage. To identify patients who would most benefit from cilostazol, this study analyzed interactions between treatment and subgroups of the PICASSO trial (Prevention of Cardiovascular Events in Asian Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage). Methods- Ischemic stroke patients with a previous intracerebral hemorrhage or multiple microbleeds were randomized to treatment with cilostazol or aspirin and followed up for a mean 1.8 years. Efficacy, defined as the composite of any stroke, myocardial infarction, and vascular death, and safety, defined as the incidence of hemorrhagic stroke, were analyzed in the 2 groups. Interactions between treatment and age, sex, presence of hypertension and diabetes mellitus, index of high-risk cerebral hemorrhage, and white matter lesion burden were analyzed for primary and key secondary outcomes. Changes in vital signs and laboratory results were compared in the 2 groups. Results- Among all 1534 patients enrolled, a significant interaction between treatment group and index of high risk for cerebral hemorrhage on hemorrhagic stroke (P for interaction, 0.03) was observed. Hemorrhagic stroke was less frequent in the cilostazol than in the aspirin group in patients with multiple microbleeds (1 versus 13 events; hazard ratio, 0.08 [95% CI, 0.01-0.61]; P=0.01). A marginal interaction between treatment group and white matter change on any stroke (P for interaction, 0.08) was observed. Cilostazol reduced any stroke significantly in patients with mild (5 versus 16 events; hazard ratio, 0.36 [95% CI, 0.13-0.97]; P=0.04)-to-moderate (16 versus 32 events; hazard ratio, 0.50 [95% CI, 0.29-0.92]; P=0.03) white matter changes. Heart rate and HDL (high-density lipoprotein) cholesterol level were significantly higher in the cilostazol group than in the aspirin group at follow-up. Conclusions- Cilostazol may be more beneficial for ischemic stroke patients with multiple cerebral microbleeds and before white matter changes are extensive. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01013532.

Bacterial Clearance Is Enhanced by α2,3- and α2,6-Sialyllactose via Receptor-Mediated Endocytosis and Phagocytosis.

Sialyllactose (SL) is a representative human milk oligosaccharide (HMO) of human breast milk. The roles of SL in infant brain development and immunity have been reported in previous studies. In this study, we identified the impact of SL on innate immunity. Our results showed that the administration of SL had significant efficacy on bacterial clearance in Pseudomonas aeruginosa K-infected mice. We also examined the role of SL in the human THP-1 macrophage-like cell line. SL effectively promoted receptor-mediated endocytosis and phagocytosis. Furthermore, SL accelerated the recruitment of Rac1 to the cell membrane, leading to the generation of reactive oxygen species for the elimination of phagocytosed bacteria. Our findings provide a new perspective on the role of SL in breast milk and suggest its application as a therapeutic agent to treat bacterial and viral infections.

Quality by Design characterization of the perfusion culture process for recombinant FVIII.

A Quality by Design (QbD) concept was applied to characterize a cell culture process for production of the recombinant Factor VIII (rFVIII). We characterized the production bioreactor process and defined the design space by applying risk assessment to determine potential critical process parameters (CPPs) impacting critical quality attributes (CQAs). Characterization studies were subsequently performed using a qualified scaled-down model (SDM) and a multi-factorial design of experiment (DOE) approach to determine both the individual and combined impacts of the potential CPPs on CQAs. Among the operating parameters characterized, production temperature, production pH and a shift in the timing of production affected rFVIII activity and tyrosine sulfation level. Finally, we identified CPPs and established a design space for the cell culture process to identify appropriate conditions for routine manufacturing.

Synthesis and Characterization of Silicon/Reduced Graphene Oxide Composites as Anodes for Lithium Secondary Batteries.

Silicon (Si) is one of the most attractive anode materials for lithium secondary batteries because of its large theoretical capacity, high safety, low cost and environmental benignity. However, Si-based anode material needs to overcome the structural change of the solid-electrolyte interphase due to the large volume change during cycling. To resolve these problems of composites by exploiting the superior conductivity, large specific surface area and flexibility of graphene, we have synthesized reduced graphene oxide (rGO)/Si composite electrode via a simple dip-coating method. Nickel foam is used as a current collector and template for the electrode fabrication. At 0.03 wt%, Si concentration, the rGO/Si composite anode presented the excellent cycle performance with large reversible capacity (778 mAh g-1 after 100 cycles). The characteristics of the rGO/Si composites were analyzed by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), Raman and X-ray photoelectron spectroscopy (XPS). The improved anode performance of the rGO/Si composite anode is ascribed to the rGO serving as a buffer layer, thereby preventing the volume expansion of Si nanoparticles, and provide facile electron pathways.

In vitro and in vivo evaluation of the genotoxicity of Eriobotrya japonica leaf extract.

Eriobotrya japonica leaf is included in the Chinese Pharmacopoeia, and is widely used as a medicinal material in traditional medicine. The present study investigated the potential genotoxic effects of E. japonica leaf extract (EJE) using three standard battery systems. Genotoxicity tests were conducted following the test guidelines of the Organisation for Economic Cooperation and Development (OECD) and Ministry of Food and Drug Safety (MFDS), with application of Good Laboratory Practice. The bacterial reverse mutation test was conducted using the pre-incubation method in the presence or absence of the metabolic activation system (S9 mixture). The in vitro chromosome aberration test was performed using cultured Chinese hamster lung cell line in the presence or absence of the S9 mixture. The in vivo micronucleus test was performed using ICR mice. The bacterial reverse mutation test with Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 and Escherichia coli strain WP2uvrA showed that EJE did not induce gene mutations at any dose level in all the strains tested. EJE also did not show any chromosomal aberrations in the in vitro chromosomal aberration test and in the in vivo micronucleus test. These results showed that EJE did not induce mutagenicity or clastogenicity in either in vitro or in vivo systems.

Diagnostic accuracy of transabdominal high-resolution US for staging gallbladder cancer and differential diagnosis of neoplastic polyps compared with EUS.

PURPOSE: To compare the diagnostic accuracy of transabdominal high-resolution ultrasound (HRUS) for staging gallbladder cancer and differential diagnosis of neoplastic polyps compared with endoscopic ultrasound (EUS) and pathology. MATERIALS AND METHODS: Among 125 patients who underwent both HRUS and EUS, we included 29 pathologically proven cancers (T1 = 7, T2 = 19, T3 = 3) including 15 polypoid cancers and 50 surgically proven polyps (neoplastic = 30, non-neoplastic = 20). We reviewed formal reports and assessed the accuracy of HRUS and EUS for diagnosing cancer as well as the differential diagnosis of neoplastic polyps. Statistical analyses were performed using chi-square tests. RESULTS: The sensitivity, specificity, PPV, and NPV for gallbladder cancer were 82.7 %, 44.4 %, 82.7 %, and 44 % using HRUS and 86.2 %, 22.2 %, 78.1 %, and 33.3 % using EUS. HRUS and EUS correctly diagnosed the stage in 13 and 12 patients. The sensitivity, specificity, PPV, and NPV for neoplastic polyps were 80 %, 80 %, 86 %, and 73 % using HRUS and 73 %, 85 %, 88 %, and 69 % using EUS. Single polyps (8/20 vs. 21/30), larger (1.0 ± 0.28 cm vs. 1.9 ± 0.85 cm) polyps, and older age (52.5 ± 13.2 vs. 66.1 ± 10.3 years) were common in neoplastic polyps (p < 0.05). CONCLUSION: Transabdominal HRUS showed comparable accuracy for diagnosing gallbladder cancer and differentiating neoplastic polyps compared with EUS. HRUS is also easy to use during our routine ultrasound examinations. KEY POINTS: • HRUS showed comparable diagnostic accuracy for GB cancer compared with EUS. • HRUS and EUS showed similar diagnostic accuracy for differentiating neoplastic polyps. • Single, larger polyps and older age were common in neoplastic polyps. • HRUS is less invasive compared with EUS.

Is obstructive sleep apnea associated with the presence of intracranial cerebral atherosclerosis?

PURPOSE: Intracranial cerebral atherosclerosis (ICAS) is one of critical atherosclerosis which closely related with stroke. Obstructive sleep apnea (OSA) is associated with systemic atherosclerosis, but it is unclear whether OSA is related with the presence of ICAS. We aimed to investigate the association between the presence of ICAS and severity of OSA in patients with suspected OSA. METHODS: This retrospective, cross-sectional study included 283 patients who suspected OSA (presence of one or more OSA-related symptom and high-risk category in Berlin questionnaire) and underwent polysomnography and brain magnetic resonance angiography (MRA). The ICAS was defined as ≥50% decrease of luminal diameter in MRA. The severity of OSA was defined by apnea-hypopnea index (AHI). RESULTS: The mean age was 60.7 ± 13.5 years, and 55.8% (158/283) were male in all included patients. The 53 (18.7%) patients had ICAS and 117 (41.3%) patients had moderate to severe OSA (AHI ≥ 15). Higher AHI was noted in patients with ICAS compared to those without ICAS (31.7 ± 25.8 versus 15.2 ± 17.4, p = 0.001). In multivariable logistic analyses, after adjusting for age, sex, and variables with p < 0.1 in univariable analyses (hypertension, diabetes mellitus, atrial fibrillation, previous stroke history, body mass index, lipid-lowing agents, arousal index, and minimum oxygen saturation), moderate to severe OSA were independently related with the presence of ICAS (odds ratio 4.17, 95% confidence interval 1.40-12.40, p = 0.010). CONCLUSIONS: Our findings suggest that moderate to severe OSA is associated with the presence of ICAS in patients with suspected OSA.

Design and Rationale of the Intima-Medial Thickness Sub-Study of the PreventIon of CArdiovascular Events in iSchemic Stroke Patients with High Risk of Cerebral hemOrrhage (PICASSO-IMT) Study.

BACKGROUND: Atherosclerosis is one of the main mechanisms of stroke and cardiovascular diseases and is associated with increased risk of recurrent stroke and cardiovascular events. Intima-medial thickness (IMT) is a well-known surrogate marker of atherosclerosis and has been used to predict stroke and cardiovascular events. However, the clinical significance of IMT and IMT change in stroke has not been investigated in well-designed studies. The PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage-Intima-Media Thickness (PICASSO-IMT) sub-study is designed to investigate the effects of cilostazol, probucol, or both on IMT in patients with stroke. METHODS: PICASSO-IMT is a prospective sub-study of the PICASSO study designed to measure IMT and plaque score at 1, 13, 25, 37, and 49 months after randomization. RESULTS: The primary outcome is the change in mean carotid IMT, which is defined as the mean of the far-wall IMTs of the right and left common carotid arteries, between baseline and 13 months after randomization. CONCLUSION: PICASSO-IMT will provide the largest IMT data set in a stroke population and will provide valuable information about the clinical significance of IMT in patients with ischemic stroke.

Type III Secretion System of Pseudomonas aeruginosa Affects Matrix Metalloproteinase 12 (MMP-12) and MMP-13 Expression via Nuclear Factor κB Signaling in Human Carcinoma Epithelial Cells and a Pneumonia Mouse Model.

The type III secretion system (T3SS) in Pseudomonas aeruginosa has been linked to severe disease and poor clinical outcomes in animal and human studies. We aimed to investigate whether the ExoS and ExoT effector proteins of P. aeruginosa affect the expression of matrix metalloproteinase 12 (MMP-12) and MMP-13 via nuclear factor κB (NF-κB) signaling pathways. To understand the T3SS, we used ΔExoS, ΔExoT, and ExsA::Ω mutants, as well as P. aeruginosa strain K (PAK)-stimulated NCI-H292 cells. We investigated the effects of ΔExoS, ΔExoT, and ExsA::Ω on the development of pneumonia in mouse models. We examined the effects of ΔExoS, ΔExoT, and ExsA::Ω on MMP-12 and MMP-13 production in NCI-H292 cells. ΔExoS and ΔExoT markedly decreased the neutrophil count in bronchoalveolar lavage fluid, with a reduction in proinflammatory mediators, MMP-12, and MMP-13. ΔExoS and ΔExoT reduced NF-κB phosphorylation, together with MMP-12 and MMP-13 expression in PAK-infected mouse models and NCI-H292 cells. To conclude, P. aeruginosa infection induced the expression of MMPs, and P. aeruginosa T3SS appeared to be a key player in MMP-12 and MMP-13 expression, which is further controlled by NF-κB signaling. These findings might be useful in devising a novel therapeutic approach to chronic pulmonary infections that involves decreasing the ExoS and ExoT levels.

Diffusion-Related MRI Parameters for Assessing Early Treatment Response of Liver Metastases to Cytotoxic Therapy in Colorectal Cancer.

OBJECTIVE: The objective of our study was to evaluate early therapeutic response after cytotoxic chemotherapy in patients with liver metastasis from colorectal cancer (CRC) using intravoxel incoherent motion (IVIM) DWI and dynamic contrast-enhanced MRI (DCE-MRI). SUBJECTS AND METHODS: Nineteen patients with liver metastasis from CRC underwent DCE-MRI and IVIM DWI at baseline and after the first cycle of chemotherapy. IVIM DWI parameters including the apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) and DCE-MRI perfusion parameters including the volume transfer constant (K(trans)), reverse volume transfer constant (Kep), extravascular extracellular volume fraction (Ve), and initial area under the concentration curve in 60 seconds (iAUC) were calculated. The response evaluation was based on Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: There were eight responding and 11 nonresponding patients. ADC (baseline value vs value after first cycle of chemotherapy [mean ± SD]: 1191.9 ± 232.2 vs 1263.5 ± 266.4 × 10(-3) mm(2)/s; p = 0.012), D (1085.9 ± 232.9 vs 1173.5 ± 248.9 × 10(-3) mm(2)/s; p = 0.012), and f (173.7% ± 39.8% vs 133.5% ± 28.3%; p = 0.017) showed a significant change after the first cycle of chemotherapy in the response group, whereas ADC and D showed no significant change in the nonresponse group. In addition, DCE-MRI perfusion parameters showed no significant changes. A correlation was found between each of perfusion-related IVIM parameters and the DCE-MRI parameters before chemotherapy (r = 1.33, p > 0.05). CONCLUSION: Diffusion-related MRI parameters are useful for the early prediction of therapeutic response after cytotoxic chemotherapy for liver metastasis from CRC.