Studies of macromolecular crowding have shown its important effects on molecular transport and interactions in living cells. Less clear is the effect of crowding when its influence is incorporated ...into a complex network of interactions. Here, we explore the effects of crowding in the cell nucleus on a model of gene transcription as a network of reactions involving transcription factors, RNA polymerases, and DNA binding sites for these proteins. The novelty of our approach is that we determine the effects of crowding on the rates of these reactions using Brownian dynamics and Monte Carlo simulations, allowing us to integrate molecular-scale information, such as the shapes and sizes of each molecular species, into the rate equations of the model. The steady-state cytoplasmic mRNA concentration shows several regimes with qualitatively different dependences on the volume fraction, ϕ, of crowding agents in the nucleus, including a broad range of parameter values where it depends nonmonotonically on ϕ, with maximum mRNA production occurring at a physiologically relevant value. The extent of this crowding dependence can be modulated by a variety of means, suggesting that the transcriptional output of a gene can be regulated jointly by the local level of macromolecular crowding in the nucleus, together with the local concentrations of polymerases and DNA-binding proteins, as well as other properties of the gene’s physical environment.
Recently, Society for Vascular Surgery guideline recommends evaluating anatomic pattern with use of Global Limb Anatomic Staging System (GLASS) in Chronic Limb-Threatening Ischemia (CLTI) patients. ...The aim of this study is to validate GLASS stage into CLTI patients on hemodialysis (HD) and investigate the impact of GLASS stage to wound healing and amputation-free survival (AFS). Between April 2009 and March 2018, we performed EVT for 154 limbs in CLTI patients on HD. GLASS was defined as femoropopliteal (FP) and infrapopliteal (IP) segments separately graded (0–4), then combined into three GLASS stages for the limb (I–III). We divided them into three GLASS stages with using this system. We compared the clinical outcomes between three groups (GLASS I, GLASS II, and GLASS III). Patient characteristics were almost similar between the three groups. Lesion characteristics was more complex and the rate of success was lower in GLASS III. Cox regression multivariate analysis revealed that diabetes mellitus (HR 2.4, 95% CI 1.37–4.01,
p
< 0.01) and WIfI high (HR 2.3, 95% CI 1.04–6.01,
p
= 0.04) were the predictors of non-wound healing, whereas age (HR 1.6, 95% CI 1.09–2.29,
p
= 0.01), WIfI clinical stage 4 (HR 2.4, 95% CI 1.30–4.36,
p
< 0.01), and non-ambulatory status (HR 2.0, 95% CI 1.17–3.29,
p
= 0.01) were the predictors of AFS. GLASS stage in CLTI patient on HD could not predict wound healing, and AFS in this study.
Objects
We aim at examining the long‐term clinical outcome after Xience everolimus‐eluting stent (X‐EES) implantation.
Background
Long‐term clinical outcomes beyond 5 years after X‐EES implantation ...remain unclear.
Methods
This retrospective study has collected data from 1184 consecutive patients, corresponding to 1463 lesions, who were treated with X‐EES alone in the Nagoya Heart Center between January 2010 and December 2013. The primary endpoint was the 10‐year cumulative incidence of target lesion failure (TLF), defined as cardiac death, target vessel myocardial infarction (MI), and clinically indicated target lesion revascularization (TLR). Definite/probable stent thrombosis (ST) was evaluated as a secondary outcome.
Results
At 10 years, the cumulative incidence of TLF was recorded to be 12.4%, whereas that of cardiac death, target vessel MI, and clinically indicated TLR was at 4.4%, 4.1%, and 7.8%, respectively. The cumulative rate of definite/probable ST was observed to remain low (0.3% at 30 days; 0.3% at 1 year; 0.6% at 5 years; and 1.1% at 10 years). In the multivariate analysis, the risk factors of TLF were insulin‐treated diabetes (hazard ratio (HR), 1.93; 95% confidence interval (CI), 1.13‐3.29; P = .02), left ventricular dysfunction (HR, 2.28; 95% CI, 1.43‐3.62; P < .01), hemodialysis (HR, 2.22; 95% CI, 1.39‐3.56; P < .01), prior percutaneous coronary intervention (HR, 1.68; 95% CI, 1.18‐2.41; P < .01), peripheral vascular disease (HR, 1.70; 95% CI, 1.07‐2.69; P < .01), severe calcification (HR, 2.08; 95% CI, 1.36‐3.09; P < .01), and in‐stent restenosis (HR, 2.93; 95% CI, 1.64‐4.89; P < .01).
Conclusions
The incidence rates of the long‐term adverse effects after X‐EES implantation, such as late TLR and ST, were determined to be low in this study; however, they increased over time until 10 years after stent implantation.
A new chronic total occlusion (CTO) guidewire, Conquest Pro 12 Sharpened Tip (CP12ST), has a stronger penetration force than the original CP12 and a deflection effect that it does not have. The ...CP12ST enables us to advance into hard plaque that has not ever penetrated, which might change CTO treatment as shown in three cases.
Background. Severely calcified coronary artery stenting remains a challenge due to stent thrombosis, target vessel failure, and higher mortality. Moreover, optimal vessel preparation for calcified ...plaque with a crack formation pattern has not been established yet. We aimed to identify the effect of crack formation in calcified plaque in the coronary artery on the lumen area after stenting. Materials and Methods. We evaluated 50 consecutive patients undergoing drug-eluting stent implantation for severely calcified lesions by using optical frequency domain imaging (OFDI) (54 lesions); we analyzed OFDI image slices every 3 mm and evaluated the segments of 242 images in those who had the arc of calcium more than 180°. Crack formation in calcified plaque was classified into three types: type 0, no cracks; type 1, no dissection between calcified plaque and vessel wall; and type 2, any dissection between calcified plaque and vessel wall. Results. Type 2 had a significantly higher area expansion ratio between preballooning and poststenting (type 0, 196% (interquartile range (IQR), 163–244); type 1, 210% (IQR, 174–244); type 2, 237% (IQR, 203–294)). Conclusions. The dissection between calcified plaque and vessel wall was a significant factor affecting lumen area expansion after stenting.
Background:Despite mounting evidence of increased cardiovascular events in patients with peripheral arterial disease (PAD), the overall incidence of cardiovascular events in PAD patients has not been ...fully clarified in Japan. The prospective Surveillance of cardiovascular Events in Antiplatelet-treated arterioSclerosis Obliterans patients in JapaN (SEASON) is a prospective observational multicenter study and here we report the baseline clinical characteristics, including atherosclerosis risk factor prevalence, in PAD patients treated with antiplatelet agents.Methods and Results:The SEASON registry enrolled 11,375 patients in 1,745 institutions and the data for 10,322 patients were analyzed. At baseline, the average age was 73.8±9.9 years, 60.0% were male and 83.9% were in Fontaine stage I or II. They had arteriosclerosis risk factors, such as current smoking (16.2%), hypertension (61.5%), diabetes mellitus (38.3%) and dyslipidemia (38.8%). There were complications including heart disease (29.7%), cerebrovascular disease (17.1%) and chronic kidney disease (14.3%). A subpopulation analysis revealed that the proportions of patients with risk factors were high in patients with lower ankle-brachial pressure index value.Conclusions:The baseline characteristics of the SEASON population demonstrate that real-world PAD patients have cardiovascular risk factors and comorbidities next to definite PAD patients. Further analysis of this database will contribute to understanding the real-world situation of PAD patients receiving antiplatelet therapy in Japan. (Circ J 2016; 80: 712–721)
Background Edaravone is widely used to treat acute ischemic stroke (AIS) within 24 hours of onset. We aimed to evaluate current edaravone treatment practices and the efficacy and safety of edaravone ...used with recombinant tissue plasminogen activator (tPA) in AIS patients within 4.5 hours of onset. The results were compared with those of the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Registry (SITS-ISTR) study. Methods PROTECT4.5 was a prospective observational study conducted from April 2010 to March 2013 in Japan. The primary end points were favorable outcomes (modified Rankin Scale score mRS 0-1) at 3 months after onset and incidence of symptomatic intracranial hemorrhage (sICH) within 36 hours of treatment. For comparison with SITS-ISTR, patients were categorized based on the time from onset to treatment (within 3 hours of and 3-4.5 hours after onset) and baseline National Institutes of Health Stroke Scale score (NIHSS). Results Among the 11,384 registered patients, 11,126 and 8274 patients were included in the safety and efficacy analysis populations, respectively. The proportions of patients with mRS 0-1 receiving edaravone alone and edaravone + tPA were 51.3% (95% confidence interval, 49.7%-52.8%) and 39.0% (37.6%-40.5%), respectively. The incidence of sICH within 36 hours after tPA treatment (edaravone + tPA group) was 1.6% (1.3%-2.0%). When compared with the SITS-ISTR results, those treated with edaravone + tPA appeared to show better outcomes in patients with NIHSS score ≥16. Conclusions The efficacy and safety of edaravone combined with tPA and administered within 4.5 hours of AIS onset were demonstrated with numerically lower incidence of sICH and better outcomes.
First of all, preparation of searching for interventional collateral channels retrogradely was planned and tip injection by a microcatheter (Caravel MC 150 cm, ASAHI INTECC) was performed in order. ......3 stents were deployed for RCA seg1-3. In particular, CTO PCI has higher risk of them compared with non-CTO PCI. ...if a guidewire went into sublumen, the smooth switching from antegrade to retrograde approach would be important because of the procedural success and increasing contrast use.
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