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The centromere, defined by the enrichment of CENP-A (a Histone H3 variant) containing nucleosomes, is a specialised chromosomal locus that acts as a microtubule attachment site. To preserve centromere identity, CENP-A levels must be maintained through active CENP-A loading during the cell cycle. A central player mediating this process is the Mis18 complex (Mis18α, Mis18ß and Mis18BP1), which recruits the CENP-A-specific chaperone HJURP to centromeres for CENP-A deposition. Here, using a multi-pronged approach, we characterise the structure of the Mis18 complex and show that multiple hetero- and homo-oligomeric interfaces facilitate the hetero-octameric Mis18 complex assembly composed of 4 Mis18α, 2 Mis18ß and 2 Mis18BP1. Evaluation of structure-guided/separation-of-function mutants reveals structural determinants essential for cell cycle controlled Mis18 complex assembly and centromere maintenance. Our results provide new mechanistic insights on centromere maintenance, highlighting that while Mis18α can associate with centromeres and deposit CENP-A independently of Mis18ß, the latter is indispensable for the optimal level of CENP-A loading required for preserving the centromere identity.
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Proteína A Centromérica , Centrómero , Centrómero/metabolismo , Proteína A Centromérica/metabolismo , Proteína A Centromérica/genética , Proteína A Centromérica/química , Humanos , Proteínas Cromosómicas no Histona/metabolismo , Proteínas Cromosómicas no Histona/química , Proteínas Cromosómicas no Histona/genética , Unión Proteica , Ciclo Celular/genética , Modelos Moleculares , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/genética , Nucleosomas/metabolismo , Nucleosomas/química , Proteínas Adaptadoras Transductoras de SeñalesRESUMEN
BACKGROUND AND AIMS: Drug-coated balloons (DCBs) have demonstrated favourable outcomes following endovascular therapy for femoropopliteal artery (FPA) disease. However, uncertainty remains whether the use of intravascular ultrasound (IVUS) can improve the outcomes of DCBs. METHODS: This prospective, multicentre, randomized trial, conducted at seven centres in South Korea, compared the outcomes of IVUS-guided vs. angiography-guided angioplasty for treating FPA disease with DCBs. Patients were assigned to receive IVUS-guided (n = 119) or angiography-guided (n = 118) angioplasty using DCBs. The primary endpoint was 12-month primary patency. RESULTS: Between May 2016 and August 2022, 237 patients were enrolled and 204 (86.0%) completed the trial (median follow-up; 363 days). The IVUS guidance group showed significantly higher primary patency [83.8% vs. 70.1%; cumulative difference 19.6% (95% confidence interval 6.8 to 32.3); P = .01] and increased freedom from clinically driven target lesion revascularization [92.4% vs. 83.0%; difference 11.6% (95% confidence interval 3.1 to 20.1); P = .02], sustained clinical improvement (89.1% vs. 76.3%, P = .01), and haemodynamic improvement (82.4% vs. 66.9%, P = .01) at 12 months compared with the angiography guidance group. The IVUS group utilized larger balloon diameters and pressures for pre-dilation, more frequent post-dilation, and higher pressures for post-dilation, resulting in a greater post-procedural minimum lumen diameter (3.90 ± 0.59 vs. 3.71 ± 0.73 mm, P = .03). CONCLUSIONS: Intravascular ultrasound guidance significantly improved the outcomes of DCBs for FPA disease in terms of primary patency, freedom from clinically driven target lesion revascularization, and sustained clinical and haemodynamic improvement at 12 months. These benefits may be attributed to IVUS-guided optimization of the lesion before and after DCB treatment.
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Angioplastia de Balón , Arteria Femoral , Enfermedad Arterial Periférica , Arteria Poplítea , Ultrasonografía Intervencional , Grado de Desobstrucción Vascular , Humanos , Ultrasonografía Intervencional/métodos , Masculino , Angioplastia de Balón/métodos , Arteria Femoral/diagnóstico por imagen , Femenino , Arteria Poplítea/diagnóstico por imagen , Enfermedad Arterial Periférica/terapia , Enfermedad Arterial Periférica/diagnóstico por imagen , Estudios Prospectivos , Anciano , Persona de Mediana Edad , Materiales Biocompatibles Revestidos , Resultado del Tratamiento , AngiografíaRESUMEN
Viroporins constitute a class of viral membrane proteins with diverse roles in the viral life cycle. They can self-assemble and form pores within the bilayer that transport substrates, such as ions and genetic material, that are critical to the viral infection cycle. However, there is little known about the oligomeric state of most viroporins. Here, we use native mass spectrometry in detergent micelles to uncover the patterns of oligomerization of the full-length SARS-CoV-2 envelope (E) protein, poliovirus VP4, and HIV Vpu. Our data suggest that the E protein is a specific dimer, VP4 is exclusively monomeric, and Vpu assembles into a polydisperse mixture of oligomers under these conditions. Overall, these results revealed the diversity in the oligomerization of viroporins, which has implications for the mechanisms of their biological functions as well as their potential as therapeutic targets.
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COVID-19 , Infecciones por VIH , Poliovirus , Humanos , SARS-CoV-2/metabolismo , Proteínas Viroporinas , Proteínas Reguladoras y Accesorias Virales , Proteínas del Virus de la Inmunodeficiencia Humana/química , Proteínas del Virus de la Inmunodeficiencia Humana/metabolismoRESUMEN
RATIONALE & OBJECTIVE: The association of long-term cumulative blood pressure (BP) loads with the risk of incident chronic kidney disease (CKD) remains a matter of debate. This study aimed to investigate this association among healthy Korean adults with normal kidney function. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We analyzed 5,221 participants without CKD in the Korean Genome and Epidemiology Study. Cumulative systolic and diastolic BP (SBP and DBP) loads were calculated as the ratios of the areas under the curve (AUC) for SBP ≥120 mmHg or ≥80 mmHg for DBP divided by the AUC for all SBP or DBP measurements during the exposure period. These AUCs were categorized into four groups: group 0 (reference), cumulative BP load of 0 and groups 1-3, tertiles of cumulative BP loads. OUTCOME: Primary endpoint was incident CKD defined as a composite of an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2 or proteinuria greater than 1+ on dipstick examination for at least two consecutive measurements ≥90 days apart. ANALYTICAL APPROACH: Multivariable Cox proportional hazards regression to estimate the independent association of cumulative BP loads with incident CKD. RESULTS: Higher cumulative SBP and DBP loads were associated with an increased risk of incident CKD (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.12-1.35 for SBP and HR 1.14, 95% CI 1.04-1.26 for DBP loads for each 1.0 unit greater load). Compared to SBP group 0, groups 2 and 3 were associated with 1.94- and 1.89-fold greater risk of incident CKD. Compared to DBP group 0, groups 2 and 3 were associated with 1.42- and 1.54-fold greater risks. These associations of high cumulative BP loads with an increased risk of incident CKD remained consistent even in subgroups not taking antihypertensive agents or without prior hypertension diagnosis. LIMITATIONS: The assessment of CKD outcomes relied on eGFR and spot urine tests. CONCLUSIONS: These findings highlight the association between high cumulative SBP and DBP loads and the occurrence of CKD, even in individuals with normal BP levels.
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Iliac artery angioplasty with stenting is an effective alternative treatment modality for aortoiliac occlusive diseases. Few randomized controlled trials have compared the efficacy and safety between self-expandable stent (SES) and balloon-expandable stent (BES) in atherosclerotic iliac artery disease. In this randomized, multicenter study, patients with common or external iliac artery occlusive disease were randomly assigned in a 1:1 ratio to either BES or SES. The primary end point was the 1-year clinical patency, defined as freedom from any surgical or percutaneous intervention due to restenosis of the target lesion after the index procedure. The secondary end point was a composite event from major adverse clinical events at 1 year. A total of 201 patients were enrolled from 17 major cardiovascular intervention centers in South Korea. The mean age of the enrolled patients was 66.8 ± 8.5 years and 86.2% of the participants were male. The frequency of critical limb ischemia was 15.4%, and the most common target lesion was in the common iliac artery (75.1%). As the primary end point, the 1-year clinical patency as primary end point was 99% in the BES group and 99% in the SES group (p > 0.99). The rate of repeat revascularization at 1 year was 7.8% in the BES group and 7.0% in the SES group (p = 0.985; confidence interval, 1.011 [0.341-2.995]). In our randomized study, the treatment of iliac artery occlusive disease with self-expandable versus balloon-expandable stent was comparable in 12-month clinical outcomes without differences in the procedural success or geographic miss rate regardless of the deployment method in the distal aortoiliac occlusive lesion (ClinicalTrials.gov, NCT01834495).
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BACKGROUND: We aimed to compare clinical outcomes between immediate and staged complete revascularization in primary percutaneous coronary intervention (PCI) for treating ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD). METHODS: A total of 248 patients were enrolled in a prospective, randomized, and multicenter registry. Immediate revascularization was defined as one-time PCI of culprit and non-culprit lesions at the initial procedure. Staged revascularization was defined as PCI of non-culprit lesions at a later date (mean, 4.4 days; interquartile range, 1-11.4), following initial culprit revascularization. The end points were major adverse cardiovascular events (MACE; composite of total death, recurrent myocardial infarction, and revascularization), any individual components of MACE, cardiac death, stent thrombosis, and stroke at 12 months. RESULTS: During a follow-up of 1 year, MACE occurred in 12 patients (11.6%) in the immediate revascularization group and in 8 patients (7.5%) in staged revascularization group (hazard ratio [HR] 1.60, 95% confidence interval [CI] 0.65-3.91). The incidence of total death was numerically higher in the immediate group than in the staged group (9.7% vs 2.8%, HR 3.53, 95% CI 0.97-12.84); There were no significant differences between the 2 groups in risks of any individual component of MACE, cardiac death, stroke, and in-hospital complications, such as need for transfusion, bleeding, acute renal failure, and acute heart failure. This study was prematurely terminated due to halt of production of everolimus-eluting stents (manufactured as PROMUS Element by Boston Scientific, Natick, Massachusetts). CONCLUSIONS: Due to its limited power, no definite conclusion can be drawn regarding complete revascularization strategy from the present study. Further large randomized clinical trials would be warranted to confirm optimal timing of complete revascularization for patients with STEMI and MVD.
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Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Accidente Cerebrovascular , Humanos , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/cirugía , Infarto del Miocardio con Elevación del ST/terapia , Intervención Coronaria Percutánea/métodos , Estudios Prospectivos , Factores de Riesgo , Resultado del Tratamiento , Accidente Cerebrovascular/etiología , Muerte , Revascularización MiocárdicaRESUMEN
SARS-CoV-2 is the novel coronavirus that is the causative agent of COVID-19, a sometimes-lethal respiratory infection responsible for a world-wide pandemic. The envelope (E) protein, one of four structural proteins encoded in the viral genome, is a 75-residue integral membrane protein whose transmembrane domain exhibits ion channel activity and whose cytoplasmic domain participates in protein-protein interactions. These activities contribute to several aspects of the viral replication-cycle, including virion assembly, budding, release, and pathogenesis. Here, we describe the structure and dynamics of full-length SARS-CoV-2 E protein in hexadecylphosphocholine micelles by NMR spectroscopy. We also characterized its interactions with four putative ion channel inhibitors. The chemical shift index and dipolar wave plots establish that E protein consists of a long transmembrane helix (residues 8-43) and a short cytoplasmic helix (residues 53-60) connected by a complex linker that exhibits some internal mobility. The conformations of the N-terminal transmembrane domain and the C-terminal cytoplasmic domain are unaffected by truncation from the intact protein. The chemical shift perturbations of E protein spectra induced by the addition of the inhibitors demonstrate that the N-terminal region (residues 6-18) is the principal binding site. The binding affinity of the inhibitors to E protein in micelles correlates with their antiviral potency in Vero E6 cells: HMA ≈ EIPA > DMA >> Amiloride, suggesting that bulky hydrophobic groups in the 5' position of the amiloride pyrazine ring play essential roles in binding to E protein and in antiviral activity. An N15A mutation increased the production of virus-like particles, induced significant chemical shift changes from residues in the inhibitor binding site, and abolished HMA binding, suggesting that Asn15 plays a key role in maintaining the protein conformation near the binding site. These studies provide the foundation for complete structure determination of E protein and for structure-based drug discovery targeting this protein.
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Amilorida/farmacología , Tratamiento Farmacológico de COVID-19 , Proteínas de la Envoltura de Coronavirus/metabolismo , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/metabolismo , Amilorida/farmacocinética , Animales , Antivirales/farmacología , Sitios de Unión/efectos de los fármacos , COVID-19/virología , Chlorocebus aethiops , Proteínas de la Envoltura de Coronavirus/química , Humanos , Canales Iónicos/metabolismo , Resonancia Magnética Nuclear Biomolecular , Unión Proteica/efectos de los fármacos , Conformación Proteica/efectos de los fármacos , Dominios Proteicos , Células Vero , Ensamble de Virus/efectos de los fármacosRESUMEN
Clinical outcomes after non-ST-segment-elevation myocardial infarction (NSTEMI) in patients with (symptom-to-door time [SDT] ≥ 24 h) or without (SDT < 24 h) delayed hospitalization among patients with or without diabetes were compared. From the Korea Acute Myocardial Infarction Registry-National Institute of Health, a total of 4517 patients with NSTEMI who underwent new-generation drug-eluting stents implantation were recruited and they were classified into the diabetes mellitus (DM) and non-DM groups. These two groups were subdivided into groups with and without delayed hospitalization. The primary clinical outcome was the occurrence of major adverse cardiac and cerebrovascular events (MACCE), defined as all-cause death, recurrent myocardial infarction, repeat coronary revascularization, and stroke. The secondary clinical outcome was the occurrence of individual components of MACCE and stent thrombosis. Although after multivariable and propensity score-adjusted analyses in the DM group, the primary and secondary clinical outcomes between the SDT < 24 h and SDT ≥ 24 h groups were similar; in the non-DM group, all-cause (p = 0.003 and p = 0.007, respectively) and cardiac (p = 0.001 and p = 0.008, respectively) death rates were significantly higher in the SDT ≥ 24 h group than in the SDT < 24 h group. Our results suggested that there was no significant difference in prognosis between diabetic patients with and without delayed SDT, but delayed SDT was associated with poor prognosis in nondiabetic patients.
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Diabetes Mellitus , Stents Liberadores de Fármacos , Infarto del Miocardio , Infarto del Miocardio sin Elevación del ST , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio sin Elevación del ST/diagnóstico por imagen , Infarto del Miocardio sin Elevación del ST/terapia , Infarto del Miocardio sin Elevación del ST/etiología , Resultado del Tratamiento , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/etiología , Infarto del Miocardio/etiología , Infarto del Miocardio/terapia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologíaRESUMEN
Shape from focus enables microscopic 3D sensing by combining it with a microscope system. However, edge bleeding artifacts of estimated depth easily occur in this environment. Therefore, this study analyzed artifacts and proposed a method to reduce edge bleeding artifacts. As a result of the analysis, the artifact factors are the depth of field of the lens, object texture, brightness difference between layers, and the slope of the object. Additionally, to reduce artifacts, a weighted focus measure value method was proposed based on the asymmetry of local brightness in artifacts. The proposed reduction method was evaluated through simulation and implementation. Edge bleeding artifact reduction rates of up to 60% were shown in various focus measure operators. The proposed method can be used with postprocessing algorithms and reduces edge bleeding artifacts.
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Ultrasonic sensors are inexpensive and provide highly accurate measurements, even with simple hardware configurations, facilitating their use in various fields. When multiple ultrasonic sensors exist in the measurement space, crosstalk occurs due to other nodes, which leads to incorrect measurements. Crosstalk includes not only receiving homogeneous signals from other nodes, but also overlapping by other signals and interference by heterogeneous signals. This paper proposes using frequency sweep keying modulation to provide robustness against overlap and a faster region-based convolutional neural network (R-CNN) demodulator to reduce the interference caused by heterogeneous signals. The demodulator works by training Faster R-CNN with the spectrograms of various received signals and classifying the received signals using Faster R-CNN. Experiments implementing an ultrasonic crosstalk environment showed that, compared to on-off keying (OOK), phase-shift keying (PSK), and frequency-shift keying (FSK), the proposed method can implement CDMA even with shorter codes and is robust against overlap. Compared to correlation-based frequency sweep keying, the time-of-flight error was reduced by approximately 75%. While the existing demodulators did not consider heterogeneous signals, the proposed method ignored approximately 99% of the OOK and PSK signals and approximately 79% of the FSK signals. The proposed method performed better than the existing methods and is expected to be used in various applications.
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The increased peripheral arterial disease (PAD) incidence associated with aging and increased incidence of cardiovascular conditions underscores the significance of assessing lower limb perfusion. This study aims to report on the correlation and utility of two novel non-invasive instruments: transcutaneous oxygen pressure (TcPO2 ) and forward-looking infrared (FLIR) thermography. A total of 68 patients diagnosed with diabetic foot ulcer and PAD who underwent vascular studies at a single institution between March 2022 and March 2023 were included. Cases with revascularization indications were treated by a cardiologist. Following the procedure, ambient TcPO2 and FLIR thermography were recorded on postoperative days 1, 7, 14, 21 and 28. In impaired limbs, TcPO2 was 12.3 ± 2 mmHg and FLIR thermography was 28.7 ± 0.9°C. TcPO2 (p = 0.002), FLIR thermography (p = 0.015) and ankle-brachial index (p = 0.047) values significantly reduced with greater vascular obstruction severity. Revascularization (n = 39) significantly improved TcPO2 (12.5 ± 1.7 to 19.1 ± 2.2 mmHg, p = 0.011) and FLIR (28.8 ± 1.8 to 32.6 ± 1.6°C; p = 0.018), especially in severe impaired angiosomes. TcPO2 significantly increased immediately post-procedure, then gradually, whereas the FLIR thermography values plateaued from day 1 to 28 post-procedure. In conclusion, FLIR thermography is a viable non-invasive tool for evaluating lower limb perfusion based on angiosomes, comparable with TcPO2 .
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Cryo-EM structures of the KMT2A/MLL1 core complex bound on nucleosome core particles (NCPs) suggest unusual rotational dynamics of the MLL1 complex approaching its physiological substrate. However, the functional implication of such dynamics remains unclear. Here, we show that the MLL1 core complex also shows high rotational dynamics bound on the NCP carrying the catalytically inert histone H3 lysine 4 to methionine (K4M) mutation. There are two major binding modes of the MLL1 complex on the NCPK4M. Importantly, disruption of only one of the binding modes compromised the overall MLL1 activity in an NCP-specific manner. We propose that the MLL1 core complex probably exists in an equilibrium of poised and active binding modes. The high rotational dynamics of the MLL1 complex on the NCP is a feature that can be exploited for loci-specific regulation of H3K4 methylation in higher eukaryotes.
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N-Metiltransferasa de Histona-Lisina/metabolismo , Proteína de la Leucemia Mieloide-Linfoide/metabolismo , Nucleosomas/metabolismo , N-Metiltransferasa de Histona-Lisina/química , N-Metiltransferasa de Histona-Lisina/ultraestructura , Histonas/metabolismo , Humanos , Metilación , Modelos Moleculares , Proteína de la Leucemia Mieloide-Linfoide/química , Proteína de la Leucemia Mieloide-Linfoide/ultraestructura , Unión Proteica , Conformación ProteicaRESUMEN
Phospholipid bicelles are valuable membrane model systems to study membrane proteins by NMR and other physicochemical techniques. The range of bicelle compositions that are compatible with uniaxial alignment of the lipid bilayers in a magnetic field is still limited with regard to the addition of large amounts (>20%) of cholesterol and/or sphingolipids. Here, we demonstrate that n-dodecyl-ß-D-melibioside (DDMB), which was recently introduced as a detergent to produce sphingolipid-cholesterol-rich isotropic bicelles for solution NMR studies, can also be used to produce magnetically alignable lipid bilayers with high cholesterol content that are well suited for solid-state NMR of membrane proteins. Remarkably, DDMB enables the preparation of high q bicelles that contain 50% mol cholesterol while retaining their ability to form a stable, well-aligned liquid crystalline bilayer phase in a magnetic field. We show that the intact 46-residue membrane-bound form of Pf1 bacteriophage coat protein and a truncated construct of the membrane protein Vpu from HIV-1 (residues 2-30) in DDMB bicelles are well aligned and undergo fast and uniaxial rotational diffusion about the bilayer normal, similarly to what is observed in other bicelle and macrodisc systems. We also demonstrate a spectroscopic method that measures the increase in the thickness of DMPC bilayers that results from the addition of cholesterol, using the PISA-wheel spectral patterns of trans-membrane helices as a molecular goniometer. For example, we find that the hydrophobic thickness of DMPC bilayers is increased by approximately 2.5 Å in the presence of 35% mol cholesterol.
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Dimiristoilfosfatidilcolina , Membrana Dobles de Lípidos , Colesterol/química , Dimiristoilfosfatidilcolina/química , Membrana Dobles de Lípidos/química , Proteínas de la Membrana , Fosfolípidos/químicaRESUMEN
Various sensors are embedded in automobiles to implement intelligent safety technologies such as autonomous driving and front-rear collision avoidance technology. In particular, ultrasonic sensors have been used in the past because they have an accuracy of centimeters to sub-centimeters in air despite their low cost and low hardware complexity. Recently, the crosstalk problem between ultrasonic sensors has been raised because the number of ultrasonic sensors in the unit space has increased as the number of vehicles increases. Various studies have been conducted to solve the crosstalk, but a demodulation error occurs when signals overlap. Therefore, in this paper, we propose a method that is robust to ultrasonic signal overlap, is robust even at shorter code length, and has reduced time of flight (TOF) error compared to the existing method by applying frequency sweep keying modulation based on code division multiple access (CDMA). As a result of the experiment, the code was detected accurately regardless of the overlap ratio of the two signals, and it was robust even in situations where the power of the two signals was different. In addition, it shows an accurate TOF estimation even if the ID code length is shorter than the existing on-off-keying, frequency shift keying, and phase shift keying methods.
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Understanding microbe-host interactions at the molecular level is a major goal of fundamental biology and therapeutic drug development. Structural biology strives to capture biomolecular structures in action, but the samples are often highly simplified versions of the complex native environment. Here, we present an Escherichia coli model system that allows us to probe the structure and function of Ail, the major surface protein of the deadly pathogen Yersinia pestis. We show that cell surface expression of Ail produces Y. pestis virulence phenotypes in E. coli, including resistance to human serum, cosedimentation of human vitronectin, and pellicle formation. Moreover, isolated bacterial cell envelopes, encompassing inner and outer membranes, yield high-resolution solid-state NMR spectra that reflect the structure of Ail and reveal Ail sites that are sensitive to the bacterial membrane environment and involved in the interactions with human serum components. The data capture the structure and function of Ail in a bacterial outer membrane and set the stage for probing its interactions with the complex milieu of immune response proteins present in human serum.
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Yersinia pestis , Proteínas de la Membrana Bacteriana Externa , Escherichia coli , Humanos , Virulencia , Factores de VirulenciaRESUMEN
BACKGROUND: Self-expanding nitinol stent (SENS) implantation is commonly oversized in the superficial femoral artery (SFA), and leads to chronic outward force (COF) and in-stent restenosis (ISR). This study aimed to investigate the impact of COF of oversizing SENS on ISR of SFA. METHODS: In patients with implanted SENS in SFA, intimal hyperplasia especially between proximal segment and distal segment was evaluated by quantitative angiography, and the impact of COF on mid-term angiographic outcomes was investigated. In addition, porcine model with implanted SENS was used to evaluate the impact of COF on angiographic and histopathologic outcomes at 1 month. Excised stented arteries were evaluated by histopathologic analysis. RESULTS: We analyzed 65 SENS in 61 patients with follow-up angiography at 6 months to 1 year. The baseline diameter was 6.8 ± 0.71 mm and length were 97.0 ± 33.8 mm for the SENS. The ratio of the diameter of the stent to the reference vessel was 1.3 ± 0.24 at the proximal portion and 1.53 ± 0.27 at the distal portion (P < 0.001). In the long SFA stent, stent-to-vessel ratio was significantly higher in the distal stent than in the proximal stent (1.3 ± 0.2 vs. 1.55 ± 0.25, P = 0.001). ISR incidence was higher at the distal stent (37.3% vs 52.6%, P = 0.029). All 11 pigs survived for 4 weeks after SENS implantation. The vessel diameter was 4.04 ± 0.40 mm (control group) vs 4.45 ± 0.63 mm (oversized group), and the implanted stent diameter was 5.27 ± 0.46 mm vs. 7.18 ± 0.4 mm (P = 0.001). The stent-to-vessel diameter ratio was 1.31 ± 0.12 versus 1.63 ± 0.20 (P < 0.001). After 4 weeks, restenosis % was 29.5 ± 12.9% versus 46.8 ± 21.5% (P = 0.016). The neointimal area was 5.37 ± 1.15 mm2 vs. 8.53 ± 5.18 mm2 (P = 0.05). The restenosis % was 39.34 ± 8.53% versus 63.97 ± 17.1% (P = 0.001). CONCLUSIONS: COF is an important cause of restenosis in the distal portion of the SFA stent. Optimal sizing of the SFA stent is important to reduce the incidence of restenosis. Therefore, COF was an important factor of restenosis following distal SFA stenting.
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Angioplastia/instrumentación , Arteria Femoral/fisiopatología , Hemodinámica , Enfermedad Arterial Periférica/terapia , Stents Metálicos Autoexpandibles , Aleaciones , Angioplastia/efectos adversos , Animales , Constricción Patológica , Femenino , Arteria Femoral/diagnóstico por imagen , Arteria Femoral/patología , Humanos , Modelos Animales , Neointima , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/patología , Enfermedad Arterial Periférica/fisiopatología , Diseño de Prótesis , Falla de Prótesis , Recurrencia , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Estrés Mecánico , Sus scrofa , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIM: This study aims to evaluate the extrinsic effects of conditional factors affecting quantitative parameters and to establish the optimization of indocyanine green (ICG) angiography using in vitro experiments and a prospective observational study. METHOD: In vitro experiments were performed to evaluate the correlation between conditional factors such as camera distance, surrounding lighting, fluorescence emission sources and ICG doses. The fluorescence intensity was measured from the ICG-containing test tube in each condition. In the clinical study, ICG angiography was applied to patients with colorectal cancer (n = 164). The quantitative perfusion parameters were the maximal fluorescence intensity (FMAX ), slope, T1/2MAX and perfusion time ratio (TR). Camera position, distance to colon, fluorescence emission source, surrounding lighting, site of angiography and ICG specific mode were considered as conditional factors and compared with the quantitative parameters to identify the optimal condition of ICG angiography. RESULTS: The fluorescence intensity had an inverse correlation with distance, and the transitional zone was shown at a distance of 4-5 cm by slope differential. FMAX , T1/2MAX and slope were affected significantly by camera distance, site of angiography, fluorescence emission source and ICG mode as conditional factors. On multivariate analysis, FMAX was independently associated with spectral ICG mode with red inversion, laser mode and camera distance. Conversely, TR was not related to any conditional factors. CONCLUSION: Since quantitative parameters of ICG angiography are influenced by various conditions, a standardized protocol is required. The application of ICG specific modes with a constant distance of 4-5 cm can provide optimized fluorescence images.
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Neoplasias Colorrectales , Cirugía Colorrectal , Laparoscopía , Fuga Anastomótica , Angiografía , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/cirugía , Angiografía con Fluoresceína , Humanos , Verde de Indocianina , PerfusiónRESUMEN
BACKGROUND: The comparative clinical outcomes between prediabetes and type 2 diabetes mellitus (T2DM) in older adults with AMI in the era of newer-generation drug-eluting stents (DES) are limited. We investigated the 2-year clinical outcomes of these patients. METHODS: A total of 5492 AMI patients aged ≥65 years were classified into three groups according to their glycemic status: normoglycemia (group A: 1193), prediabetes (group B: 1696), and T2DM (group C: 2603). The primary outcome was the occurrence of major adverse cardiac events (MACE), defined as all-cause death, recurrent myocardial infarction (Re-MI), and any repeat revascularization. The secondary outcome was stent thrombosis (ST). RESULTS: The primary and secondary outcomes cumulative incidences were similar between the prediabetes and T2DM groups. In both the prediabetes and T2DM groups, the cumulative incidences of MACE (adjusted hazard ratio [aHR]: 1.373; p = 0.020 and aHR: 1.479; p = 0.002, respectively) and all-cause death or MI (aHR: 1.436; p = 0.022 and aHR: 1.647; p = 0.001, respectively) were significantly higher than those in the normoglycemia group. Additionally, the cumulative incidence of all-cause death in the T2DM group was significantly higher than that in the normoglycemia group (aHR, 1.666; p = 0.003). CONCLUSIONS: In this retrospective study, despite the 2-year clinical outcomes of the patients with prediabetes and T2DM in the older adults were worse than those in the normoglycemia group; they were similar between the prediabetes and T2DM groups. Hence, comparable treatment strategies should be strengthened between prediabetes and T2DM in older adults with AMI. TRIAL REGISTRATION: Retrospectively registered.
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Diabetes Mellitus Tipo 2 , Stents Liberadores de Fármacos , Infarto del Miocardio , Intervención Coronaria Percutánea , Estado Prediabético , Anciano , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Humanos , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/epidemiología , Intervención Coronaria Percutánea/efectos adversos , Estado Prediabético/diagnóstico , Estado Prediabético/epidemiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Optimal stenting strategy for long femoropopliteal artery lesions still remains undefined. Longer stent length has been shown to be associated with increased risk of restenosis. We sought to compare the efficacy of spot versus long stenting in the treatment of femoropopliteal artery disease. METHODS: This study was designed as a multicenter randomized controlled trial to compare immediate and mid-term outcomes of spot versus long primary stenting for femoropopliteal arterial lesions. A total of 125 patients were randomized 1:1 to spot stenting group (n = 59) or long stenting group (n = 66). RESULTS: All lesions were treated with self-expanding bare nitinol stents. Baseline clinical and lesion characteristics were similar between the 2 groups except for male gender and current smoker. The mean lesion length was 24.1 ± 8.8 cm. Technical success was achieved in all patients. The 1-year primary patency and TLR-free (target lesion revascularization) survival did not differ significantly between the 2 groups. However, the spot stenting group showed a trend toward higher primary patency (86.1% vs. 72.7%, P = 0.158) and TLR-free survival (94.2% vs. 82.5%, P = 0.120). The total stented length (hazard ratio [HR] 1.01, 95% confidence interval [CI] 1.00-1.01, P = 0.011) and age (HR 0.94, 95% CI 0.90-1.00, P = 0.035) were independent predictors of restenosis. CONCLUSIONS: The spot stenting appears to be more favorable than the long stenting in terms of primary patency and TLR-free survival, although the difference was not statistically significant. The stented length was an independent predictor of restenosis.
Asunto(s)
Angioplastia de Balón/instrumentación , Arteria Femoral , Enfermedad Arterial Periférica/terapia , Arteria Poplítea , Stents Metálicos Autoexpandibles , Anciano , Aleaciones , Angioplastia de Balón/efectos adversos , Angioplastia de Balón/métodos , Constricción Patológica , Femenino , Arteria Femoral/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/fisiopatología , Arteria Poplítea/fisiopatología , Supervivencia sin Progresión , Diseño de Prótesis , Recurrencia , República de Corea , Factores de Riesgo , Factores de Tiempo , Grado de Desobstrucción VascularRESUMEN
Human endothelial-overexpressed lipopolysaccharide-associated factor 1 (EOLA1) has been suggested to regulate inflammatory responses in endothelial cells by controlling expression of proteins, interleukin-6 and vascular cell adhesion molecule-1, and by preventing apoptosis. To elucidate the structural basis of the EOLA1 function, we determined its crystal structure at 1.71 Å resolution and found that EOLA1 is structurally similar to an activating signal cointegrator-1 homology (ASCH) domain with a characteristic ß-barrel fold surrounded by α-helices. Despite its low sequence identity with other ASCH domains, EOLA1 retains a conserved 'GxKxxExR' motif in its cavity structure. The cavity harbors aromatic and polar residues, which are speculated to accommodate nucleotide molecules as do YT521-B homology (YTH) proteins. Additionally, EOLA1 exhibits a positively charged cleft, similar to those observed in YTH proteins and the ASCH protein from Zymomonas mobilis that exerts ribonuclease activity. This implies that the positively charged cleft in EOLA1 could stabilize the binding of RNA molecules. Taken together, we suggest that EOLA1 controls protein expression through RNA binding to play protective roles against endothelial cell injuries resulting from lipopolysaccharide (LPS)-induced inflammation responses.