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Housing roughly 10 million head of cattle in the United States alone, open air cattle feedlots represent a significant but poorly constrained source of atmospheric particles. Here we present a comprehensive characterization of physical and chemical properties of particles emitted from a large representative cattle feedlot in the Southwest United States. In the summer of 2008, measurements and samplings were conducted at the nominally upwind and downwind edges of the facility. A series of far-field measurements and samplings was also conducted 3.5 km north of the facility. Two instruments, a GRIMM Sequential Mobility Particle Sizer (SMPS) and a GRIMM Portable Aerosol Spectrometer (PAS), were used to measure particle size distributions over the range of 0.01 to 25 µm diameter. Raman microspectroscopy (RM) was used to determine the chemical composition of particles on a single particle basis. Volume size distributions of fugitive dust were dominated by coarse mode particles. Twenty-four hour averaged concentrations of PM10 (particulate matter with a diameter of 10 µm or less) were as high as 1200 µg m-3 during the campaign. The primary constituents of the particulate matter were carbonaceous materials, such as humic acid, water soluble organics, and less soluble fatty acids, including stearic acid and tristearin. A significant percentage of the organic particles, up to 28 %, were composed of internally mixed with salts. Basic characteristics such as size distribution and composition of agricultural aerosols were found to be different than the properties of those found in urban and semi-urban aerosols. Failing to account for such differences will lead to serious errors in estimates of aerosol effects on climate, visibility, and public health. [ABSTRACT FROM AUTHOR]

Open-lot, concentrated animal feeding operations (CAFOs) in the southern High Plains, such as cattle feed-yards and open-lot dairies, emit fugitive particulate matter (PM) that occasionally reduces downwind visibility. The long-path visibility transmissometer (LPV) can be used to measure changes in total atmospheric extinction, a direct measure of path-averaged visibility impairment. To our knowledge, no researchers have used transmissometry as a surrogate to estimate aerosol concentrations downwind of open-lot livestock facilities. We compare time-resolved PM mass concentrations (µg m-3) and atmospheric extinction coefficients (km-1) measured simultaneously along the downwind boundary of a commercial cattle feedyard to compute "extinction efficiency," the change in atmospheric extinction that results from a unit change in PM mass concentration. Expected values for the in-situ extinction efficiency of total suspended particulate (TSP) and its fraction less than 10 microns (PM10) aerodynamic equivalent diameter (AED) are 0.2 to 0.5 m² g-1 and 0.4 to 0.8 m² g-1, respectively. Determination of the atmospheric extinction efficiency of feedyard dust will enable transmissometry to be used as an intuitive, real-time surrogate for measuring time-averaged PM10 and/or TSP concentrations. [ABSTRACT FROM AUTHOR]

Paroxysmal cold hemoglobinuria (PCH) is a rare disease in adults, and its concurrent presentation with warm-type autoimmune hemolytic anemia (AIHA) has not yet been reported. We encountered a 19-year-old woman with AIHA and a positive Donath-Landsteiner test result identified by a hemolytic attack during blood transfusion. She also showed positive results for the direct Coombs and Donath-Landsteiner antibody tests. After treatment with prednisolone followed by rituximab, the AIHA improved, and the Donath-Landsteiner antibody test result turned negative. Clinicians should be aware that patients may present with concurrent warm-type AIHA and PCH and consider rituximab for its treatment.

Introduction: The CD34 + CD38 - population in bone marrow includes hematopoietic stem/progenitor cells. Recently, in acute myeloid leukemia, the focus has shifted to flow cytometry analysis targeting CD34 + CD38 - leukemic cells due to their effectiveness in minimal/measurable residual disease detection and prognosis prediction. Nevertheless, the immunophenotype and cell frequency of these cells in the bone marrow, in the absence of leukemic cells, remains unknown. We aimed to evaluate detailed characteristics of CD34 + CD38 - cells in both normal and leukemic cells by flow cytometry., Methods: We compared the cell frequency and immunophenotype of the CD34 + CD38 - fraction in the following groups: patients with idiopathic thrombocytopenic purpura and malignant lymphoma as controls (n = 17), post-treatment patients without abnormal blasts (n = 35), and patients with myeloid malignancies (n = 86). The comparison was based on the presence or absence of CD45RA expression, a marker commonly used to prospectively isolate lymphoid-primed cell populations within the CD34 + CD38 - fraction., Results: The CD34 + CD38 - CD45RA + cell population exhibited a significant expansion in bone marrow without leukemic cells 1 month after cord blood transplantation and in various type of myeloid malignancies, compared to the control group (p < 0.01). Continuous CD45RA expression and notable expansion of the CD34 + CD38 - CD45RA - population were exclusively observed in myelodysplastic syndrome-related diseases. The CD34 + CD38 - CD45RA + population displayed frequent expression of various markers in both leukemic and non-leukemic cells, in contrast to the CD34 + CD38 - CD45RA - population., Conclusions: The CD34 + CD38 - fraction should be carefully evaluated considering the nature of normal hematopoietic precursor cells, their cell frequency and immunophenotype, including CD45RA expression pattern, for improving the accuracy of myeloid malignancy diagnosis., (© 2023 International Clinical Cytometry Society.)

This paper introduces hands-on curricular modules integrated with research in atmospheric ice nucleation, which is an important phenomenon potentially influencing global climate change. The primary goal of this work is to promote meaningful laboratory exercises to enhance the competence of students in the fields of science, technology, engineering, and math (STEM) by applying an appropriate methodology to laboratory ice nucleation measurements. To achieve this goal, three laboratory modules were developed with 18 STEM interns and tested by 28 students in a classroom setting. Students were trained to experimentally simulate atmospheric ice nucleation and cloud droplet freezing. For practical training, this work utilized a simple freezing assay device called the West Texas Cryogenic Refrigerator Applied to Freezing Test (WT-CRAFT) system. More specifically, students were provided with hands-on lessons to calibrate WT-CRAFT with deionized water and apply analytical techniques to understand the physicochemical properties of bulk water and droplet freezing. All procedures to implement the developed modules were typewritten during this process, and shareable read-ahead exploration materials were developed and compiled as a curricular product. Additionally, students conducted complementary analyses to identify possible catalysts of heterogeneous freezing in the water. The water analyses included: pH, conductivity, surface tension, and electron microscopy-energy-dispersive X-ray spectroscopy. During the data and image analysis process, students learned how to analyze droplet freezing spectra as a function of temperature, screen and interpret the data, perform uncertainty analyses, and estimate ice nucleation efficiency using computer programs. Based on the formal program assessment of learning outcomes and direct (yet deidentified) student feedback, we broadly achieved our goals to (1) improve their problem-solving skills by combining multidisciplinary science and math skills and (2) disseminate data and results with variability and uncertainty. The developed modules can be applied at any institute to advance undergraduate and graduate curricula in environmental science., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society and Division of Chemical Education, Inc.)

The trRosetta structure prediction method employs deep learning to generate predicted residue-residue distance and orientation distributions from which 3D models are built. We sought to improve the method by incorporating as inputs (in addition to sequence information) both language model embeddings and template information weighted by sequence similarity to the target. We also developed a refinement pipeline that recombines models generated by template-free and template utilizing versions of trRosetta guided by the DeepAccNet accuracy predictor. Both benchmark tests and CASP results show that the new pipeline is a considerable improvement over the original trRosetta, and it is faster and requires less computing resources, completing the entire modeling process in a median < 3 h in CASP14. Our human group improved results with this pipeline primarily by identifying additional homologous sequences for input into the network. We also used the DeepAccNet accuracy predictor to guide Rosetta high-resolution refinement for submissions in the regular and refinement categories; although performance was quite good on a CASP relative scale, the overall improvements were rather modest in part due to missing inter-domain or inter-chain contacts., (© 2021 The Authors. Proteins: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC.)

We develop a deep learning framework (DeepAccNet) that estimates per-residue accuracy and residue-residue distance signed error in protein models and uses these predictions to guide Rosetta protein structure refinement. The network uses 3D convolutions to evaluate local atomic environments followed by 2D convolutions to provide their global contexts and outperforms other methods that similarly predict the accuracy of protein structure models. Overall accuracy predictions for X-ray and cryoEM structures in the PDB correlate with their resolution, and the network should be broadly useful for assessing the accuracy of both predicted structure models and experimentally determined structures and identifying specific regions likely to be in error. Incorporation of the accuracy predictions at multiple stages in the Rosetta refinement protocol considerably increased the accuracy of the resulting protein structure models, illustrating how deep learning can improve search for global energy minima of biomolecules.

Background: Analysis of pooled clinical data has shown the safety of 3 months of dual antiplatelet therapy with everolimus-eluting cobalt-chromium stents (Co-Cr EESs). This study evaluated early and mid-term vascular responses to Co-Cr EESs in patients with stable coronary artery disease., Methods: The Multicenter Comparison of Early and Late Vascular Responses to Everolimus-Eluting Cobalt-Chromium Stent and Platelet Aggregation Studies in Patients With Stable Angina Managed as Elective Case (MECHANISM-Elective) study (NCT02014818) is a multicenter optical coherence tomography (OCT) registry. Enrolled patients were evaluated by OCT immediately after everolimus-eluting stent implantation were prospectively allocated to 1 month (n = 50) or 3 months (n = 50) OCT follow-up and then received a 12-month OCT evaluation. The incidences of intrastent thrombus (IS-Th) and irregular protrusion (IRP) were also assessed., Results: The percentage of uncovered struts was 6.4% ± 10.3% at 1 month (P < 0.001 vs. postprocedure) and 0.5% ± 0.9% at 12 months (P < 0.001 vs. 1 month). The corresponding values in the 3-month cohort were 2.0% ± 2.5% (P < 0.001 vs. postprocedure) and 0.5% ± 1.5% (P < 0.001 vs. 3 months). The incidence of IS-Th was 32.7% at 1 month, 5.4% at 3 months, and 2.0% at 12 months. IRP was observed in 21.8% of patients post-EES but had totally resolved at 1, 3, and 12 months., Conclusion: Early and mid-term vascular reactions after Co-Cr EES implantation in stable patients with coronary artery disease in the MECHANISM-Elective included dynamic resolution of IS-Th and IRP and rapid decrease in uncovered struts. Thus, EES may allow shortening of dual antiplatelet therapy duration less than 3 months in this patient subset., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

ChIP-seq is a technique to determine binding locations of transcription factors, which remains a central challenge in molecular biology. Current practice is to use a 'control' dataset to remove background signals from a immunoprecipitation (IP) 'target' dataset. We introduce the AIControl framework, which eliminates the need to obtain a control dataset and instead identifies binding peaks by estimating the distributions of background signals from many publicly available control ChIP-seq datasets. We thereby avoid the cost of running control experiments while simultaneously increasing the accuracy of binding location identification. Specifically, AIControl can (i) estimate background signals at fine resolution, (ii) systematically weigh the most appropriate control datasets in a data-driven way, (iii) capture sources of potential biases that may be missed by one control dataset and (iv) remove the need for costly and time-consuming control experiments. We applied AIControl to 410 IP datasets in the ENCODE ChIP-seq database, using 440 control datasets from 107 cell types to impute background signal. Without using matched control datasets, AIControl identified peaks that were more enriched for putative binding sites than those identified by other popular peak callers that used a matched control dataset. We also demonstrated that our framework identifies binding sites that recover documented protein interactions more accurately., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Intra-stent thrombus (IS-Th) formed immediately after percutaneous coronary intervention (PCI) is associated with subsequent adverse coronary events. However, the impact of on-treatment platelet reactivity on IS-Th is unknown. PRASFIT-Elective is a multicenter study of PCI patients receiving prasugrel (20/3.75 mg, loading/maintenance dose) or clopidogrel (300/75 mg), with aspirin (100 mg). Among the 742 study patients, 111 were pre-specified for the OCT sub-study. Of these, 82 underwent OCT immediately after PCI to assess IS-Th and at an 8-month follow-up to evaluate the fate of the IS-Th. Lesions were considered resolved when IS-Th were detected after PCI but not on the follow-up or persistent when IS-Th were observed on both scans. The P2Y12 Reactive Unit (PRU) value was determined at the initial PCI and 4 and 48 weeks post-PCI. In 76 patients (86 lesions), we detected 230 IS-Th initially, and 196 IS-Th (85.2%) were resolved at the 8-month OCT. At PCI, but not 4 or 48 weeks after, the resolved IS-Th group had a lower PRU than the persistent IS-Th group (199 ± 101 vs. 266 ± 102, p = 0.008). Multivariate logistic regression analyses revealed that lower PRU at PCI and less calcified lesions were independent predictive factors for the resolution of IS-Th. Local lesion-related factors and lower on-treatment platelet reactivity at the time of PCI may contribute to the resolution of IS-Th after EES implantation, potentially improving clinical outcome.

Sexual reproduction roots the eukaryotic tree of life, although its loss occurs across diverse taxa. Asexual reproduction and clonal lineages persist in these taxa despite theoretical arguments suggesting that individual clones should be evolutionarily short-lived due to limited phenotypic diversity. Here, we present quantitative evidence that an obligate asexual lineage emerged from a sexual population of the marine diatom Thalassiosira pseudonana and rapidly expanded throughout the world's oceans. Whole genome comparisons identified two lineages with characteristics expected of sexually reproducing strains in Hardy-Weinberg equilibrium. A third lineage displays genomic signatures for the functional loss of sexual reproduction followed by a recent global colonization by a single ancestral genotype. Extant members of this lineage are genetically differentiated and phenotypically plastic, potentially allowing for rapid adaptation when they are challenged by natural selection. Such mechanisms may be expected to generate new clones within marginal populations of additional unicellular species, facilitating the exploration and colonization of novel environments, aided by exponential growth and ease of dispersal.

Objectives: This study sought to investigate the effect of daily glucose fluctuation on coronary plaque properties in patients with coronary artery disease (CAD) pre-treated with lipid-lowering therapy., Background: There is growing evidence that glucose fluctuation, as a residual risk apart from dyslipidemia, is an important factor contributing to the development of CAD., Methods: This prospective study enrolled 70 consecutive CAD patients who were referred for percutaneous coronary intervention and whose low-density lipoprotein cholesterol level was <120 mg/dl under statin treatment or <100 mg/dl without statins. Daily glucose fluctuation was analyzed by measuring the mean amplitude of glycemic excursion (MAGE). The plaque properties in the culprit and nonculprit lesions were assessed by virtual histology intravascular ultrasound, and the volume percentage of necrotic core within the plaque (%NC) and the presence of thin-cap fibroatheroma were evaluated., Results: In total, 165 lesions were evaluated in 70 patients (40 diabetic and 30 nondiabetic patients). %NC was well correlated with MAGE (r = 0.490, p <0.001). A linear mixed effect model showed that MAGE had the strongest effect on %NC (coefficient β = 0.080 ± 0.020 [standard error], p < 0.001). The generalized linear mixed effect model revealed that MAGE was the only independent predictor of the presence of thin-cap fibroatheroma (odds ratio: 1.037; 95% confidence interval: 1.010 to 1.065; p = 0.007)., Conclusions: Daily glucose fluctuation may have an effect on coronary plaque vulnerability in patients with CAD pre-treated with lipid-lowering therapy. Further investigations should address the rationale for the early detection and control of glucose fluctuation in the era of universal statin use for CAD patients., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Essential thrombocythemia (ET) has been reported to cause acute coronary disease. However, the efficacy of anti-platelet therapy for ET is unclear since there are individual differences in the platelet function of ET patients. Here we report a case of a 62-year-old man with ET who was admitted to our hospital because of acute coronary syndrome. He underwent coronary angioplasty. Dual anti-platelet therapy with aspirin (81 mg/day) and clopidogrel (75 mg/day) was subsequently initiated. We evaluated platelet reactivity in P2Y12 reaction units, and subsequently determined anti-platelet drugs and corresponding doses. < Learning objective: Essential thrombocythemia (ET) is a myeloproliferative disorder that causes acute coronary disease. As there are individual differences in the platelet function of patients with ET, the efficacy of anti-platelet therapy for these patients varies. Evaluation of platelet reactivity using P2Y12 reaction units is useful in determining appropriate anti-platelet drugs and corresponding doses.>.

Background: Previous reports have suggested the importance of delayed arterial healing and the development of neoatherosclerosis as major contributors to stent thrombosis and delayed restenosis. The difference of in vivo assessment of long-term vessel healing between first-generation drug-eluting stents and current generation everolimus-eluting stents (EESs) is limited. The aim of this study was to evaluate long-term arterial healing in EES in comparison with the first generation sirolimus-eluting stents (SES)., Methods: We evaluated 31 EES (23 patients) and 8 SES (7 patients) by serial optical coherence tomography at 12 months (mid-phase) and 24 months (late-phase) after stenting and evaluated the change in neointimal thickness (NIT), the percentages of uncovered struts, peri-strut low intensity area (PLIA; region around stent struts homogenously lower-intensity appearance than surrounding tissue), and thrombus., Results: Although the average NIT showed no significant changes from the mid- to the late-phase follow-up in both EES and SES groups, the change in NIT and minimum lumen area was significantly larger in SES than EES (5.2±29.4 vs. 37.2±48.9; p=0.02, -0.06±0.36 vs. -0.45±0.74; p=0.04, respectively). The incidence of uncovered struts and struts with PLIA of EES was lower than those of SES, at both phases. Stents with in-stent thrombus of EES tended to be lower than that of SES at both phase follow-ups., Conclusion: Although both SES and EES showed progressive luminal narrowing from the mid- to the late-phase follow-up, the extent of delayed lumen narrowing and delayed neointimal proliferation was significantly less in the second generation EES than the first generation SES. EESs seem to offer sustained stability in efficacy, without sacrificing safety, up to 2 years after implantation., (Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Aims: Biodegradable polymer-based drug-eluting stents are thought to be safer than durable polymer-based stents. However, the long-term vascular response remains unclear. The aim of this study was to compare the biocompatibility of durable polymer-based sirolimus-eluting (SES) and everolimus-eluting (EES) stents with biodegradable polymer-based biolimus-eluting (BES) stents in a porcine coronary model. Stents were implanted in porcine coronaries. Acetylcholine challenge tests and optical coherence tomography (OCT) examination were performed at one month. Animals were sacrificed at three and six months (n=6 each), and the stents were analysed histologically. At one month, acetylcholine challenge tests revealed a trend towards greatest vasoconstriction in SES, less in BES, and least in EES, but the differences were not significant. OCT analysis demonstrated the highest incidence of uncovered struts in SES, followed by BES, while EES showed almost complete strut coverage (41.7±27.0%, 24.5±23.8%, 0.4±0.8%, respectively; p=0.004). Upon histological analysis at three months, SES showed a significantly higher inflammatory score than BES and EES (2.9±1.4, 0.8±0.9, 0.5±0.4, respectively; p=0.001), and this was maintained at six months (1.6±1.5, 0.3±0.3, 0.4±0.6, respectively; p=0.049). While SES showed an increased inflammatory reaction, EES and BES showed minimal inflammation. These results indicate that the late inflammatory reaction does not necessarily depend on degradability of the polymer, if the combination of the drug, metal, and polymer is biocompatible.

Background: Although drug-eluting stents have significantly reduced the midterm incidence of target lesion revascularization (TLR), in vivo studies on long-term vessel healing of sirolimus-eluting stents (SESs) and paclitaxel-eluting stents (PESs) are limited. The aim of this study was to compare long-term arterial healing with SESs and PESs., Methods: We evaluated 27 SESs (23 patients) and 21 PESs (20 patients) by serial optical coherence tomography at 6 months (midphase) and ≥ 3 years (late phase) after stenting and evaluated the change of neointimal thickness (NIT), the percentages of uncovered and malapposed struts, peristrut low-intensity area (region around stent struts with a homogeneously lower intensity appearance than surrounding tissue), thrombus, and atherogenic neointima., Results: At follow-up, most SESs showed a progressive increase in the average NIT, whereas PESs showed variable changes. Between midphase and late phase, NIT increased significantly in SESs (midphase, 94.1 ± 49.3; late phase, 130.2 ± 78.7; P = 0.001) but decreased significantly in PESs (midphase, 167.4 ± 122.9; late phase, 136.0 ± 77.7; P = 0.04). The percentages of uncovered struts decreased significantly in SESs; conversely, variable changes were observed in PESs. Peristrut low-intensity area and thrombus formation decreased in SESs but remained largely unchanged in PESs. The prevalence of atherogenic neointima was greater in the late phase than in the midphase in both groups but was similar for both stents., Conclusions: Long-term vessel healing was different for SESs and PESs. Progressive vessel healing was consistently observed in SESs, whereas a heterogeneous process of delayed vessel healing was noted for PESs., (Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Although hemodialysis (HD) is a suggested risk factor for stent thrombosis, its contribution to local vessel healing after drug-eluting stent (DES) implantation is unclear., Methods: A total of 121 patients (152 lesions treated with DES) who underwent 8-month follow-up coronary angiography with optical coherence tomography (OCT) were enrolled, and the findings were compared between patients with and without HD. To match baseline differences, mid-term OCT findings of 42 propensity score-matched lesions (21 non-HD vs. 21 HD) were compared. Effects of HD on the efficacy of antiplatelet therapy were also evaluated by VerifyNow assay (Accumetrics, San Diego, CA, USA)., Results: Patients with HD had a significantly higher rate of thrombus formation than those without (64% vs. 33%, p = 0.007), although the baseline parameters and lesion characteristics differed between the groups. Multivariate logistic regression analysis revealed that HD was associated with an increased risk of thrombus formation (odds ratio 5.991, 95% confidence interval: 1.972-18.199, p = 0.002). Even after propensity-matching for patient background and balancing of angiographic and OCT variables, the risk of thrombus formation remained significantly higher in HD patients. The P2Y12-reaction unit was significantly increased after HD (Pre HD: 211 ± 75 vs. Post HD: 262 ± 59, p = 0.01), but patients without HD showed no increase during the same elapsed time (221 ± 88 vs. 212 ± 96, p = 0.19)., Conclusions: HD is a potential risk factor for subclinical thrombus attachment after DES therapy. Systemic problems, such as residual platelet reactivity, associated with HD as well as local vessel features in HD patients might contribute to the increased incidence of thrombus attachment and subsequent onset of thrombotic event after DES implantation., (Copyright © 2013. Published by Elsevier Ltd.)

The consequences of acute strut malapposition in everolimus-eluting stents (EES) are unknown. This study investigated the impact of strut-vessel (S-V) distance and plaque type underneath acute strut malapposition on the mid-term vessel response in EES. Twenty-nine patients (35 EES) underwent optical coherence tomography (OCT) immediately after percutaneous coronary intervention and at 8-month follow-up. S-V distance and plaque type (lipid, calcified, or fibrous) underneath acute strut malapposition were evaluated. Follow-up OCT classified acute strut malapposition as persistent or resolved. The S-V cutoff value for predicting resolved strut malapposition and the incidence of intra-stent thrombi were determined. Among 569 cases of acute strut malapposition, involving 29,168 struts, 139 (24.4 %) were persistent. Mean S-V distance was significantly longer in persistent than in resolved strut malapposition (600 ± 294 vs. 231 ± 95 μm; P < 0.0001). S-V distance ≤380 μm was the best cutoff value for predicting resolved strut malapposition (sensitivity 93.5 %, specificity 69.8 %, area under curve 0.878). Acute strut malapposition with S-V distance ≤380 μm remained persistent more frequently over lipid/calcified than over fibrous plaques (lipid: 13.4 %, calcified: 18.2 %, fibrous: 4.2 %; lipid vs. fibrous, P = 0.001; calcified vs. fibrous, P = 0.02). Intra-stent thrombi were more frequent in stents with ≥1 persistent strut malapposition than in those without [4/11 stents (36.3 %) vs. 0/24 (0 %); P = 0.006]. Lipid and calcified plaque, together with S-V distance, affect the resolution of acute strut malapposition in EES. Persistent strut malapposition is associated with the presence of thrombi at follow-up, which could be the substrate for late stent thrombosis.

Background: The addition of highly purified eicosapentaenoic acid (EPA) to statin therapy prevents cardiovascular events. However, the impact of this treatment on vulnerable plaques remains unclear. The aim of this study was to assess the impact of adding EPA to a standard statin therapy on vulnerable plaques by serial optical coherence tomography (OCT)., Methods: Forty-nine non-culprit thin-cap fibroatheroma (TCFA) lesions in 30 patients with untreated dyslipidemia were included. Patients were randomly assigned to EPA (1800 mg/day) + statin (23 TCFA, 15 patients) or statin only (26 TCFA, 15 patients) treatment. The statin (rosuvastatin) dose was adjusted to achieve a target low-density lipoprotein (LDL) level of <70 mg/dL. Post-percutaneous intervention and 9-month follow-up OCT were performed to evaluate morphological changes of TCFAs. The EPA/arachidonic acid (EPA/AA) ratio and pentraxin-3 (PTX3) levels were also evaluated., Results: Despite similar follow-up LDL levels, the EPA + statin group had higher EPA/AA ratios and lower PTX3 levels than the statin group. OCT analysis showed that the EPA + statin group had a greater increase in fibrous-cap thickness, with a greater decrease in lipid arc and lipid length. Macrophage accumulation was less frequently detected in the EPA + statin group than in the statin group at follow-up. When the patients were categorized according to their follow-up PTX3 tertiles, fibrous-cap thickness showed significant increase, and the incidence of macrophages accumulation decreased with lower PTX3 levels., Conclusion: The concomitant use of EPA and rosuvastatin may stabilize vulnerable plaques better than the statin alone, possibly by suppressing arterial inflammation., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: This study directly compared optical coherence tomography (OCT) and histopathology for the assessment of vascular response to first- and second-generation drug-eluting stents. METHODS AND RESULTS: Sirolimus-, everolimus-, and biolimus-eluting stents (SES, EES, and BES, respectively) were randomly implanted into the coronary arteries of 12 porcine. OCT was conducted after implantation: at 1, 3, and 6 months; histopathology was assessed at 3 and 6 months. At 1-month OCT, EES had the highest neointimal area (NA) and lowest neointimal unevenness score (NUS). At 6 months, NA and NUS were equivalent among the stent types. ∆NA from 1 to 6 months was lowest for EES, and ∆NA correlated with the histopathological inflammation score at 6 months, which was highest for SES (P<0.001). The mean signal intensity (MSI) and the attenuation were different for the stent types at 3 months, and were associated with inflammation score. Moderate diagnostic efficiency for measuring MSI was found, with an optimal cut-off of 6.88 predicting a high (≥grade 3) inflammation score., Conclusions: EES had the greatest uniformity and the least neointimal proliferation and were associated with less persistent inflammation. OCT provides accurate morphometric data; furthermore, quantitative measurement of the optical properties may help assess histological inflammation, which was more predominantly associated with SES than with EES and BES.

Background: Previous reports have shown potential disadvantages of limus-derivative drugs for the stenting treatment of patients with diabetes mellitus (DM). METHODS AND RESULTS: We studied 159 coronary artery lesions (DM: n=72, non-DM: n=87) in 123 patients treated with everolimus-eluting stent (EES) and who underwent scheduled 9-month follow-up angiography with optical coherence tomography (OCT) regardless of symptoms. In addition to standard OCT variables, neointimal unevenness score (maximum/average neointimal thickness) and stent eccentricity index (minimum/maximum stent diameter) were calculated for each cross-section. To investigate a potential baseline difference between DM and non-DM lesions, pre- and post-interventional intravascular ultrasound (IVUS) images were also evaluated as an IVUS subgroup analysis. The average neointimal thickness and neointimal coverage did not differ between DM and non-DM patients. DM patients had, however, greater asymmetric stent expansion and variability of neointimal thickness than non-DM patients. There was a weak, but significant association between average stent eccentricity index and neointimal unevenness score. The IVUS substudy showed that the culprit plaque volume and plaque eccentricity in DM patients were significantly greater than in non-DM patients., Conclusions: Although EES provided a similar level of average neointimal thickness and coverage both in the presence and absence of DM, uneven neointimal suppression occurred in DM patients. A larger plaque volume of the culprit lesion may hamper symmetric stent expansion, possibly explaining the non-uniform neointimal suppression in DM patients.

Background: Although both optical coherence tomography (OCT) and angioscopy are robust tools for detecting intrastent thrombi and neoatherosclerosis in vivo, whether OCT findings are comparable with angioscopy findings remains unclear., Methods and Results: 22 patients presenting with de novo lesions underwent 26 sirolimus-eluting stent (SES) implantations, with follow-up OCT and angioscopy at 10 months post-implantation for segmental assessment of the proximal, mid-, and distal SES segments (66 segments). The mean signal intensity index (signal intensity of the neointima/signal intensity of fibrous intimal hyperplasia) was quantified for angioscopically detected in-stent yellow and white segments. The detection rate for red thrombi was numerically higher with angioscopy than with OCT (17% vs. 9%; P=0.053). Angioscopically detected in-stent yellow segments were categorized into 3 OCT patterns: "high-attenuation tissue covering struts" (OCT-defined neoatherosclerosis), "high-attenuation tissue underneath struts," and "low-attenuation and low-intensity tissue covering struts"; further, macrophage-like appearance was most frequently observed with OCT-defined neoatherosclerosis (56%, 6.3%, and 0%, respectively, P<0.001). The mean signal intensity index of neoatherosclerosis was significantly lower than that of angioscopically detected in-stent white segments (0.929 vs. 0.997, P=0.004)., Conclusions: Current OCT-based definitions for thrombus detection may underestimate the presence of subclinical red thrombi. Qualitative and quantitative OCT assessments of the neointima may enhance the detection of neoatherosclerosis over SES in vivo.

Background: Nobori is a novel biolimus A9-eluting stent (BES) coated with a biodegradable polymer only on the abluminal side, which degrades over 6-9 months post-stent deployment. The course of vessel reaction after deployment at these time points remains unclear., Methods and Results: We serially evaluated 28 BES implanted in de novo coronary lesions of 23 patients using optical coherence tomography (OCT) at 6 and 12 months post-stenting. Standard OCT variables, the percentage of stent with peri-strut low-intensity area (PLIA, a region around stent struts homogenously showing lesser intensity than the surrounding tissue, suggesting fibrin deposition or impaired neointima maturation) and that with in-stent thrombi were evaluated. There was a significant, but small increase in neointimal thickness (72 ± 23 to 82 ± 25 µm, P=0.006) from the 6- to the 12-month follow-up, without a significant decrease in minimum lumen area (P=0.30). The incidences of uncovered and malapposed struts were low at 6 months and reduced further at 12 months (3.96 ± 3.97% to 1.51 ± 1.63%, P=0.001, and 0.50 ± 1.84% to 0.06 ± 0.24%, P=0.20, respectively). The frequency of stent with PLIA decreased during the follow-up (57% to 32%, P=0.05) and that with in-stent thrombi also numerically decreased (7% to 0%, P=0.24)., Conclusions: Neointimal hyperplasia was persistently suppressed following BES implantation up to 12 months. Simultaneously, favorable vessel healing was achieved at 6 months without a delaying adverse reaction for up to 12 months.

Background: The impact of paraoxonase-1 (PON1) activity on the response to clopidogrel may differ in patients treated with drug-eluting stents (DES) in association with CYP2C19 loss-of-function (LOF) polymorphisms., Methods: This study included 112 Japanese patients receiving clopidogrel (75 mg/day) and aspirin (100mg/day) who underwent optical coherence tomography (OCT) examination 9 months after DES implantation. The CYP2C19 genotype was analyzed and LOF carriers (1/2, 1/3, 2/2, 3/3, 2/3) were identified. At the 9-month follow-up, platelet reactivity was determined by measuring the P2Y12 reactivity unit (PRU) using a VerifyNow P2Y12 assay, PON1 activity was evaluated and intra-stent thrombus was evaluated by OCT., Results: Of the 112 Japanese patients, 75 were LOF carriers (67.0%). The patients were divided into tertiles according to the PON1 activity (tertile 1; <230 U/L, tertile 2; 230-283U/L, tertile 3; >283 U/L). In the VerifyNowP2Y12 analysis, tertile 1 had a higher PRU than tertiles 2 and 3 in LOF carriers, and there was no difference among tertiles in non-carriers. The highest incidence of intra-stent thrombus was observed in tertile 1 followed by tertiles 2 and 3 in LOF carriers, whereas there was no such difference in non-carriers. Multivariate analysis revealed that LOF carriers and PON1 activity tertile 1 were independent predictors of intra-stent thrombus in all patients. In LOF carriers, tertile 1 was the only independent predictor for intra-stent thrombus., Conclusion: Low PON1 activity is associated with a low response to clopidogrel and a high frequency of intra-stent thrombus only in LOF carriers., (© 2013.)

Aims: We performed this study to clarify natural consequences of abnormal structures (stent malapposition, thrombus, tissue prolapse, and stent edge dissection) after percutaneous coronary intervention (PCI)., Methods and Results: Thirty-five patients treated with 40 drug-eluting stents underwent serial optical coherence tomography (OCT) imaging immediately after PCI and at the 8-month follow-up. Among a total of 73 929 struts in every frame, 431 struts (26 stents) showed malapposition immediately after PCI. Among these, 49 remained malapposed at the follow-up examination. The mean distance between the strut and vessel wall (S-V distance) of persistent malapposed struts on post-stenting OCT images was significantly longer than that of resolved malapposed struts (342 ± 99 vs. 210 ± 49 μm; P <0.01). Based on receiver-operating characteristic curve analysis, an S-V distance ≤260 µm on post-stenting OCT images was the corresponding cut-off point for resolved malapposed struts (sensitivity: 89.3%, specificity: 83.7%, area under the curve = 0.884). Additionally, 108 newly appearing malapposed struts were observed on follow-up OCT, probably due to thrombus dissolution or plaque regression. Thrombus was observed in 15 stents post-PCI. Serial OCT analysis revealed persistent thrombus in 1 stent, resolved thrombus in 14 stents, and late-acquired thrombus in 8 stents. Tissue prolapse observed in 38 stents had disappeared at the follow-up. All eight stent edge dissections were repaired at the follow-up., Conclusion: Most cases of stent malapposition with a short S-V distance, thrombus, tissue prolapse, or minor stent edge dissection improved during the follow-up. These OCT-detected minor abnormalities may not require additional treatment.