Case report: Stenosis turned leak … and turned stenosis-complications of paravalvular prosthetic leak closure with a plug device.

Paravalvular leak is one of the most common complications and is among the most important prognostic factors of short- and long-term mortality after transcatheter aortic valve implantation (TAVI). Percutaneous valvular leak repair constitutes a first-line treatment for paravalvular leaks and is associated with high success rates and few serious complications nowadays. To the best of our knowledge, this is the first case where placement of the device through the stenting of the bioprosthesis resulted in creating a new symptomatic stenosis that required surgery. We present a case of a patient with low-flow, low-gradient aortic stenosis treated with transfemoral implantation of a biological aortic prosthesis. One month after the procedure, the patient presented with acute pulmonary oedema and a paravalvular leak was discovered, which was corrected by percutaneous repair with a plug device. Five weeks after the valvular leak repair, the patient was readmitted for heart failure. At this time, a new aortic stenosis and paravalvular leak were diagnosed and the patient was referred for surgery. The new aortic mixed diseased was caused by the positioning of the plug device through the valve's metal stenting, which resulted in a paravalvular leak and pressed against the valve's leaflets, causing valvular stenosis. The patient was referred for surgical replacement and evolved well afterward. This case illustrates a rare complication of a complex procedure, and it highlights the need for multidisciplinary decisions and good cooperation between the cardiology and cardiac surgery teams to develop better criteria in the selection of the appropriate technique for managing paravalvular leaks after TAVI

Ability of FFR-CT to detect the absence of hemodynamically significant lesions in patients with high-risk NSTE-ACS admitted in the emergency department with chest pain, study design and rationale.

In the era of High-sensitive troponin (hs-Tn), up to 50% of patients with a mild increase of hs-Tn will finally have a normal invasive coronary angiogram. Fractional Flow Reserve (FFR) derived from coronary computed tomographic angiography (FFR-CT) has never been used as a non-invasive tool for the diagnosis of coronary artery disease in patients with high-risk acute coronary syndrome without ST segment elevation (NSTE-ACS). The study aims to determine the role of coronary CT angiography and FFR-CT in the setting of high-risk NSTE-ACS. We will conduct a prospective trial, enrolling 250 patients admitted with high-risk NSTE-ACS who will rapidly undergo a coronary CT angiography and then a coronary angiography with FFR measurements. Results of coronary CT, FFR-CT and coronary angiography (± FFR) will be compared. In conclusion, non-invasive identification of patients with high-risk NSTE-ACS who could avoid coronary angiography would reduce procedure related risks and medical costs

Occupational choice, number of entrepreneurs and output: theory and empirical evidence with Spanish data

This paper extends the (Lucas, Bell J Econ 9:508–523,1978) model of occupational choices by individuals with different skills, beyond the simple options of self-employment or wage-employment, by including a second choice for the self-employed. That is, an option to hire employees and so become self-employed with employees (SEWEs), or to be self-employed without employees (SEWNEs). We solve for the market equilibrium and examine the sensitivity of relative sizes of occupational groups, and of the level of productivity, to changes in the exogenous parameters. The results show that the positive (negative) association between number of SEWEs (SEWNEs) and productivity, observed in the Spanish data, can be explained, under certain conditions, as the result of cross-region and time differences in average skills. These findings point to the importance of distinguishing between SEWEs and SEWNEs in drawing valid conclusions concerning any link between entrepreneurship and economic development

Comparative Long-Term Effect of Three Anti-P2Y12 Drugs after Percutaneous Angioplasty: An Observational Study Based on Electronic Drug Adherence Monitoring

Aims: Dual platelet inhibition using anti-P2Y12 drugs and aspirin is the standard of care in patients after percutaneous coronary interventions (PCI). Prasugrel and ticagrelor have been shown to be more potent than clopidogrel with less high on-treatment platelet reactivity. Whether differences in long-term adherence to these drugs can partly explain different antiplatelet efficacy has not been studied so far. The objective was to compare the long-term P2Y12 receptor inhibition and drug adherence to different anti-P2Y12 drugs, and to assess the impact of adherence on the pharmacodynamic effect.Methods: Monocentric, prospective, observational study. Stable outpatients treated with clopidogrel 75 mg once daily, prasugrel 10 mg once daily or ticagrelor 90 mg twice daily after PCI with stent implantation were included. Drug adherence was recorded during 6 months using electronic monitoring. Platelet responsiveness was assessed with the vasodilator-stimulated phosphoprotein platelet reactivity index (VASP-PRI) at inclusion, 3 and 6 months.Results: 120 patients had VASP-PRI and adherence data available. At 6-months, mean VASP-PRI (±SD) was 17.7 ± 11.0% with ticagrelor, 29.2 ± 15.5% with prasugrel and 47.2 ± 17.6% with clopidogrel (ANOVA, P < 0.0001).Median [IQR] taking adherence was 96 [82–100]% with ticagrelor, 100 [97–101]% with prasugrel and 100 [99–101]% with clopidogrel (p = 0.0001). Median [IQR] correct dosing was 88 [73–95]% with ticagrelor, 97 [92.5–98]% with prasugrel and 98 [96–99]% with clopidogrel (p = 0.0001).Anti-P2Y12 drug (p ≤ 0.001) and diabetes (p = 0.014) emerged as predictors of poor antiplatelet response after adjusting for age, BMI, sex, and CYP2C19∗2 carriers status.Conclusion: Drug adherence to anti-P2Y12 drugs assessed with electronic monitoring was very high. However, anti-P2Y12 drugs showed significant differences in antiplatelet activity, with newer anti-P2Y12 drugs ticagrelor and prasugrel exerting a stronger P2Y12 receptor inhibition.These data suggest that pharmacokinetic-pharmacodynamic differences between oral anti-P2Y12 drugs are more important than adherence in determining antiplatelet efficacy when adherence to prescription is high.The study was registered (Current Controlled Trials ISRCTN85949729)

Detection of Burkholderia in the seeds of Psychotria punctata (Rubiaceae) – Microscopic evidence for vertical transmission in the leaf nodule symbiosis

<div><p>Background and aims</p><p>The bacterial leaf nodule symbiosis is a close interaction between endophytes and their plant hosts, mainly within the coffee family. The interaction between Rubiaceae species and <i>Burkholderia</i> bacteria is unique due to its obligate nature, high specificity, and predominantly vertical transmission of the endophytes to the next generation of host plants. This vertical transmission is intriguing since it is the basis for the uniqueness of the symbiosis. However, unequivocal evidence of the location of the endophytes in the seeds is lacking. The aim of this paper is therefore to demonstrate the presence of the host specific endophyte in the seeds of <i>Psychotria punctata</i> and confirm its precise location. In addition, the suggested location of the endophyte in other parts of the host plant is investigated.</p><p>Methods</p><p>To identify and locate the endophyte in <i>Psychotria punctata</i>, a two-level approach was adopted using both a molecular screening method and fluorescent <i>in situ</i> hybridisation microscopy.</p><p>Key results</p><p>The endophytes, molecularly identified as <i>Candidatus</i> Burkholderia kirkii, were detected in the leaves, vegetative and flower buds, anthers, gynoecium, embryos, and young twigs. In addition, they were <i>in situ</i> localised in leaves, flowers and shoot apical meristems, and, for the first time, in between the cotyledons of the embryos.</p><p>Conclusions</p><p>Both independent techniques detected the host specific endophyte in close proximity to the shoot apical meristem of the embryo, which confirms for the first time the exact location of the endophytes in the seeds. This study provides reliable proof that the endophytes are maintained throughout the growth and development of the host plant and are transmitted vertically to the offspring.</p></div

Variational Principle underlying Scale Invariant Social Systems

MaxEnt's variational principle, in conjunction with Shannon's logarithmic information measure, yields only exponential functional forms in straightforward fashion. In this communication we show how to overcome this limitation via the incorporation, into the variational process, of suitable dynamical information. As a consequence, we are able to formulate a somewhat generalized Shannonian Maximum Entropy approach which provides a unifying "thermodynamic-like" explanation for the scale-invariant phenomena observed in social contexts, as city-population distributions. We confirm the MaxEnt predictions by means of numerical experiments with random walkers, and compare them with some empirical data

Performance of highly sensitive cardiac troponin T assay to detect ischaemia at PET-CT in low-risk patients with acute coronary syndrome: a prospective observational study.

Highly sensitive troponin T (hs-TnT) assay has improved clinical decision-making for patients admitted with chest pain. However, this assay's performance in detecting myocardial ischaemia in a lowrisk population has been poorly documented. To assess hs-TnT assay's performance to detect myocardial ischaemia at positron emission tomography/CT (PET-CT) in low-risk patients admitted with chest pain. Patients admitted for chest pain with a nonconclusive ECG and negative standard cardiac troponin T results at admission and after 6 hours were prospectively enrolled. Their hs-TnT samples were at T0, T2 and T6. Physicians were blinded to hs-TnT results. All patients underwent a PET-CT at rest and during adenosine-induced stress. All patients with a positive PET-CT result underwent a coronary angiography. Forty-eight patients were included. Six had ischaemia at PET-CT. All of them had ≥1 significant stenosis at coronary angiography. Areas under the curve (95% CI) for predicting significant ischaemia at PET-CT using hs-TnT were 0.764 (0.515 to 1.000) at T0, 0.812(0.616 to 1.000) at T2 and 0.813(0.638 to 0.989) at T6. The receiver operating characteristicbased optimal cut-off value for hs-TnT at T0, T2 and T6 needed to exclude significant ischaemia at PET-CT was &lt;4 ng/L. Using this value, sensitivity, specificity, positive and negative predictive values of hs-TnT to predict significant ischaemia were 83%/38%/16%/94% at T0, 100%/40%/19%/100% at T2 and 100%/43%/20%/100% at T6, respectively. Our findings suggest that in low-risk patients, using the hs-TnT assay with a cut-off value of 4 ng/L demonstrates excellent negative predictive value to exclude myocardial ischaemia detection at PET-CT, at the expense of weak specificity and positive predictive value. ClinicalTrials.gov Identifier: NCT01374607

Relationship between CMR-derived parameters of ischemia/reperfusion injury and the timing of CMR after reperfused ST-segment elevation myocardial infarction.

To investigate the influence of cardiovascular magnetic resonance (CMR) timing after reperfusion on CMR-derived parameters of ischemia/reperfusion (I/R) injury in patients with ST-segment elevation myocardial infarction (STEMI). The study included 163 reperfused STEMI patients undergoing CMR during the index hospitalization. Patients were divided according to the time between revascularization and CMR (T &lt;sub&gt;revasc-CMR&lt;/sub&gt; : Tertile-1 ≤ 43; 43 &lt; Tertile-2 ≤ 93; Tertile-3 &gt; 93 h). T2-mapping derived area-at-risk (AAR) and intramyocardial-hemorrhage (IMH), and late gadolinium enhancement (LGE)-derived infarct size (IS) and microvascular obstruction (MVO) were quantified. T1-mapping was performed before and &gt; 15 min after Gd-based contrast-agent administration yielding extracellular volume (ECV) of infarct. Main factors influencing I/R injury were homogenously balanced across T &lt;sub&gt;revasc-CMR&lt;/sub&gt; tertiles. T2 values of infarct and remote regions increased with increasing T &lt;sub&gt;revasc-CMR&lt;/sub&gt; tertiles (infarct: 60.0 ± 4.9 vs 63.5 ± 5.6 vs 64.8 ± 7.5 ms; P &lt; 0.001; remote: 44.3 ± 2.8 vs 46.1 ± 2.8 vs ± 46.1 ± 3.0; P = 0.001). However, T2 value of infarct largely and significantly exceeded that of remote myocardium in each tertile yielding comparable T2-mapping-derived AAR extent throughout T &lt;sub&gt;revasc-CMR&lt;/sub&gt; tertiles (17 ± 9% vs 19 ± 9% vs 18 ± 8% of LV, respectively, P = 0.385). Similarly, T2-mapping-based IMH detection and quantification were independent of T &lt;sub&gt;revasc-CMR&lt;/sub&gt; . LGE-derived IS and MVO were not influenced by T &lt;sub&gt;revasc-CMR&lt;/sub&gt; (IS: 12 ± 9% vs 12 ± 9% vs 14 ± 9% of LV, respectively, P = 0.646). In 68 patients without MVO, T1-mapping based ECV of infarct region was comparable across T &lt;sub&gt;revasc-CMR&lt;/sub&gt; tertiles (P = 0.470). In STEMI patients, T2 values of infarct and remote myocardium increase with increasing CMR time after revascularization. However, these changes do not give rise to substantial variation of T2-mapping-derived AAR size nor of other CMR-based parameters of I/R. ISRCTN03522116 . Registered 30.4.2018 (retrospectively registered)

Establishment of proximity-dependent biotinylation approaches in different plant model systems

Proximity labeling is a powerful approach for detecting protein-protein interactions. Most proximity labeling techniques use a promiscuous biotin ligase (PBL) or a peroxidase fused to a protein of interest, enabling the covalent biotin labelling of proteins and subsequent capture and identification of interacting and neighbouring proteins without the need for the protein complex to remain intact. To date, only few papers report on the use of proximity labeling in plants. Here, we present the results of a systematic study applying a variety of biotin-based proximity labeling approaches in several plant systems using various conditions and bait proteins. We show that TurboID is the most promiscuous variant in several plant model systems and establish protocols which combine Mass Spectrometry-based analysis with harsh extraction and washing conditions. We demonstrate the applicability of TurboID in capturing membrane-associated protein interactomes using Lotus japonicus symbiotically active receptor kinases as test-case. We further benchmark the efficiency of various PBLs in comparison with one-step affinity purification approaches. We identified both known as well as novel interactors of the endocytic TPLATE complex. We furthermore present a straightforward strategy to identify both non-biotinylated as well as biotinylated peptides in a single experimental setup. Finally, we provide initial evidence that our approach has the potential to infer structural information of protein complexes