Plastic fiber-optic probes for characterizing fluidized beds in bubbling regime

Bubble measurements on a fluidized bed in bubbling regime using optical fibre probes (OFP) are reported. Comparisons between commercial pressure transducers (PT) measurements and OFP have also been carried out. OFP are able to detect smaller bubbles than the PT and reflect more localized phenomena in the bed.Publicad

Short-term Effects of Overnight Orthokeratology on Corneal Sub-basal Nerve Plexus Morphology and Corneal Sensitivity

Objective: To assess the effects of a short period of orthokeratology (OK) on corneal subbasal nerve plexus (SBNP) morphology and corneal sensitivity. Methods: Measurements were made in 56 right eyes of 56 subjects with low-to-moderate myopia who wore 2 OK lens designs (Group CRT: HDS 100 Paragon CRT, n=35; Group SF: Seefree; n=21) for a period of 1 month and in 15 right eyes of noncontact lens wearers as controls. The variables determined in each participant were corneal sensitivity using a Cochet-Bonnet esthesiometer and 12 SBNP variables determined on laser scanning confocal microscopy images using 3 different software packages. Correlation between SBNP architecture and corneal sensitivity was also examined. Results: Few changes were observed over the 1-month period in the variables examined in the OK treatment and control groups. However, significant reductions were detected over time in the number of nerves in the central cornea in the groups CRT (P=0.029) and SF (P=0.043) and in central corneal sensitivity in CRT (P=0.047) along with significant increases in central and midperipheral corneal Langerhans cell counts in SF (P=0.001 and 0.048, respectively). Conclusions: This study provides useful data to better understand the anatomical changes induced by OK in corneal SBNP. The different response observed to the 2 OK lens designs requires further investigation

Long-Term Impacts of Orthokeratology Treatment on Sub-Basal Nerve Plexus and Corneal Sensitivity Responses and Their Reversibility

Purpose: To examine the effects of one year of overnight orthokeratology (OK) treatment on the sub-basal nerve plexus (SBNP) and corneal sensitivity and to assess the reversibility of these effects one month after treatment interruption. Methods: Thirty-two subjects with low-moderate myopia underwent OK treatment for one year. Fifteen non-contact lens wearers served as controls. At the time points baseline, one year of treatment, and one month after removing the OK lenses, two tests were conducted: corneal sensitivity (Cochet-Bonnet esthesiometer) and SBNP imaging by in vivo confocal microscopy. Results: In participants wearing OK lenses, significant reductions over the year were produced in SBNP nerve density (P=0.001 and P=0.006) and number of nerves (P<0.001 and P=0.001) in the central and mid-peripheral cornea, respectively. Differences over the year were also detected in central objective tortuosity (P=0.002). After lens removal, baseline values of nerve density (P=0.024 and P=0.001) and number of nerves (P=0.021 and P<0.001) for the central and mid-peripheral cornea, respectively, were not recovered. At one month post-treatment, a difference was observed from one-year values in central corneal sensitivity (P=0.045) and mid-peripheral Langerhans cell density (P=0.033), and from baseline in mid-peripheral objective tortuosity (P=0.049). Direct correlation was detected at one year between nerve density and tortuosity both in the central (P<0.01; r=0.69) and mid-peripheral cornea (P<0.01; r=0.76). Conclusions: Long-term OK treatment led to reduced SBNP nerve density and this was directly correlated with corneal tortuosity. After one month of treatment interruption, nerve density was still reduced

Genomic profiling of fungal cell wall-interfering compounds: identification of a common gene signature

[Background]: The fungal cell wall forms a compact network whose integrity is essential for cell morphology and viability. Thus, fungal cells have evolved mechanisms to elicit adequate adaptive responses when cell wall integrity (CWI) is compromised. Functional genomic approaches provide a unique opportunity to globally characterize these adaptive mechanisms. To provide a global perspective on these CWI regulatory mechanisms, we developed chemical-genomic profiling of haploid mutant budding yeast cells to systematically identify in parallel those genes required to cope with stresses interfering the cell wall by different modes of action: β-1,3 glucanase and chitinase activities (zymolyase), inhibition of β-1,3 glucan synthase (caspofungin) and binding to chitin (Congo red). [Results]: Measurement of the relative fitness of the whole collection of 4786 haploid budding yeast knock-out mutants identified 222 mutants hypersensitive to caspofungin, 154 mutants hypersensitive to zymolyase, and 446 mutants hypersensitive to Congo red. Functional profiling uncovered both common and specific requirements to cope with different cell wall damages. We identified a cluster of 43 genes highly important for the integrity of the cell wall as the common >signature of cell wall maintenance (CWM)>. This cluster was enriched in genes related to vesicular trafficking and transport, cell wall remodeling and morphogenesis, transcription and chromatin remodeling, signal transduction and RNA metabolism. Although the CWI pathway is the main MAPK pathway regulating cell wall integrity, the collaboration with other signal transduction pathways like the HOG pathway and the invasive growth pathway is also required to cope with the cell wall damage depending on the nature of the stress. Finally, 25 mutant strains showed enhanced caspofungin resistance, including 13 that had not been previously identified. Only three of them, wsc1δ, elo2δ and elo3δ, showed a significant decrease in β-1,3-glucan synthase activity. [Conclusions]: This work provides a global perspective about the mechanisms involved in cell wall stress adaptive responses and the cellular functions required for cell wall integrity. The results may be useful to uncover new potential antifungal targets and develop efficient antifungal strategies by combination of two drugs, one targeting the cell wall and the other interfering with the adaptive mechanisms.This work was supported by grants BIO2010-22146, BIO2013-48136-P (MINECO, Spain) and S2010/BMD-2414 (Comunidad de Madrid) to J.A, and grant BIO2012-35372 (MINECO, Spain) to JCR.Peer Reviewe

Outcomes after TAVI in patients with atrial fibrillation and a history of recent PCI:Results from the ENVISAGE-TAVI AF trial

Background: Patients with atrial fibrillation (AF) and a recent (≤ 90 days) percutaneous coronary intervention (PCI) undergoing transcatheter aortic valve implantation (TAVI) are at high bleeding risk due to the addition of oral antiplatelet (OAP) agents on top of oral anticoagulants. Data on outcomes of these patients are needed to optimize antithrombotic treatment. Methods: This analysis compared annualized clinical event rates in patients with and without a recent PCI enrolled in ENVISAGE-TAVI AF, a prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban and vitamin K antagonists in AF patients after TAVI. The primary efficacy and safety outcomes were net adverse clinical events (NACE) and major bleeding. Results: Overall, 132 (94.3%) patients with a recent PCI (n = 140) received OAP after TAVI, compared with 692 (55.9%) patients without a recent PCI (n = 1237). Among patients with a recent PCI on OAP agents, use of dual antiplatelet therapy decreased to 5.5%, and use of single antiplatelet therapy (SAPT) increased to 78.0% over 3 months post-randomization. Conversely, use of SAPT predominated at all time points in patients without a recent PCI history. There were no significant differences in the incidence of NACE or other outcomes assessed, except for major bleeding events, which were more frequent in patients with vs without a recent PCI history (hazard ratio [95% confidence interval]: 2.17 [1.27, 3.73]; P = 0.005). Conclusions: Patients with AF undergoing TAVI with a recent PCI have a similar risk of ischemic events and mortality, but an increased risk of major bleeding compared with patients without a recent PCI. Graphical abstract: [Figure not available: see fulltext.].</p

Tratamiento percutáneo de insuficiencia mitral severa por rotura de neocuerdas

Percutaneous mitral valve repair techniques have raised substantial interest in recent years, because they allow treating serious lesions avoiding surgical complications with good results in well-selected patients. Echocardiography is absolutely essential in the transcatheter mitral repair procedure and in the selection of candidates for this technique. We present a clinical case of percutaneous edge-to-edge mitral repair treatment in a patient with recurrence of severe mitral regurgitation after having previously undergone neochordal implantation, in which echocardiography played an essential role.Las técnicas de reparación mitral percutánea han generado mucho interés en los últimos años ya que permiten tratar lesiones graves evitando las complicaciones quirúrgicas y con buenos resultados en pacientes bien seleccionados. La ecocardiografía es completamente imprescindible en la reparación mitral transcatéter y en la selección de pacientes candidatos a esta técnica. Presentamos un caso clínico de tratamiento percutáneo de reparación mitral borde a borde en una paciente con recurrencia de insuficiencia mitral grave tras haber sido previamente intervenida con el implante de neocuerdas en el que rol de la ecocardiografía fue esencial

Eco-fusión. Aplicación en el intervencionismo estructural cardíaco

The evolution in percutaneous structural intervention has generated a parallel development in advanced imaging techniques. Echocardiography plays a key role in structural intervention in patient selection, assessment during the fluoroscopy and immediate analysis of outcomes and early detection of complications; echo-fusion images appear as a complementary tool in which two techniques with dynamic images are complemented in a single image in order to guide, decrease intervention time and reduce complications.La evolución en el intervencionismo estructural percutáneo ha generado un desarrollo paralelo en las técnicas de imagen avanzada. La ecocardiografía en el intervencionismo estructural juega un papel básico en la selección de los pacientes, en la valoración durante el procedimiento y en el análisis inmediato de los resultados y la detección precoz de complicaciones. Las imágenes de fusión eco/fluoroscopia aparecen como una herramienta complementaria en la que dos técnicas con imágenes dinámicas se complementan en una sola imagen con el fin de orientar, disminuir el tiempo de intervención y disminuir las complicaciones

Baseline ECG and prognosis after transcatheter aortic valve implantation: the role of interatrial block

Background: The clinical significance of conduction disturbances after transcatheter aortic valve implantation has been described; however, little is known about the influence of baseline ECGs in the prognosis of these patients. Our aim was to study the influence of baseline ECG parameters, including interatrial block (IAB), in the prognosis of patients treated with transcatheter aortic valve implantation. Methods and Results: The BIT (Baseline Interatrial Block and Transcatheter Aortic Valve Implantation) registry included 2527 patients with aortic stenosis treated with transcatheter aortic valve implantation. A centralized analysis of baseline ECGs was performed. Patients were divided into 4 groups: normal P wave duration (<120 ms); partial IAB (P wave duration ≥120 ms, positive in the inferior leads); advanced IAB (P wave duration ≥120 ms, biphasic [+/-] morphology in the inferior leads); and nonsinus rhythm (atrial fibrillation/flutter and paced rhythm). The mean age of patients was 82.6±9.8 years and 1397 (55.3%) were women. A total of 960 patients (38.0%) had a normal P wave, 582 (23.0%) had partial IAB, 300 (11.9%) had advanced IAB, and 685 (27.1%) presented with nonsinus rhythm. Mean follow‐up duration was 465±171 days. Advanced IAB was the only independent predictor of all‐cause mortality (hazard ratio [HR], 1.48; 95% CI, 1.10-1.98 [P=0.010]) and of the composite end point (death/stroke/new atrial fibrillation) (HR, 1.51; 95% CI, 1.17-1.94 [P=0.001]). Conclusions: Baseline ECG characteristics influence the prognosis of patients with aortic stenosis treated with transcatheter aortic valve implantation. Advanced IAB is present in about an eighth of patients and is associated with all‐cause death and the composite end point of death, stroke, and new atrial fibrillation during follow‐up

Interaction between SARS-CoV PBM and Cellular PDZ Domains Leading to Virus Virulence

The interaction between SARS-CoV PDZ-binding motifs (PBMs) and cellular PDZs is responsible for virus virulence. The PBM sequence present in the 3a and envelope (E) proteins of SARS-CoV can potentially bind to over 400 cellular proteins containing PDZ domains. The role of SARS-CoV 3a and E proteins was studied. SARS-CoVs, in which 3a-PBM and E-PMB have been deleted (3a-PBM-/E-PBM-), reduced their titer around one logarithmic unit but still were viable. In addition, the absence of the E-PBM and the replacement of 3a-PBM with that of E did not allow the rescue of SARS-CoV. E protein PBM was necessary for virulence, activating p38-MAPK through the interaction with Syntenin-1 PDZ domain. However, the presence or absence of the homologous motif in the 3a protein, which does not bind to Syntenin-1, did not affect virus pathogenicity. Mutagenesis analysis and in silico modeling were performed to study the extension of the PBM of the SARS-CoV E protein. Alanine and glycine scanning was performed revealing a pair of amino acids necessary for optimum virus replication. The binding of E protein with the PDZ2 domain of the Syntenin-1 homodimer induced conformational changes in both PDZ domains 1 and 2 of the dimer.This work was supported by grants from the Government of Spain (PID2022-140328OB-I00, MCIN/AEI/10.13039/501100011033/FEDER, UE; PID2019-107001RB-I00 AEI/FEDER, UE and PIE_INTRAMURAL_LINEA 1-202020E079), CSIC (PIE_INTRAMURAL -202020E043), the European Zoonotic Anticipation and Preparedness Initiative (ZAPI) (IMI_JU_115760), the European Commission (H2020-SC1-2019, ISOLDA Project No. 848166-2), and the U.S. National Institutes of Health (NIH) (2P01AI060699). JMH received a contract from Comunidad de Madrid (Y2020/BIO- 6576, COVID-PREclinical-MODels-CM).Peer reviewe

Impact of operatoŕs experience on peri-procedural outcomes with Watchman FLX: Insights from the FLX-SPA registry

Background: The Watchman FLX is a device upgrade of the Watchman 2.5 that incorporates several design enhancements intended to simplify left atrial appendage occlusion (LAAO) and improve procedural outcomes. This study compares peri-procedural results of LAAO with Watchman FLX (Boston Scientific, Marlborough, Massachusetts) in centers with varying degrees of experience with the Watchman 2.5 and Watchman FLX. Methods: Prospective, multicenter, 'real-world' registry including consecutive patients undergoing LAAO with the Watchman FLX at 26 Spanish sites (FLX-SPA registry). Implanting centers were classified according to the center's prior experience with the Watchman 2.5. A further division of centers according to whether or not they had performed ≤ 10 or > 10Watchman FLX implants was prespecified at the beginning of the study. Procedural outcomes of institutions stratified according to their experience with the Watchman 2.5 and FLX devices were compared. Results: 359 patients [mean age 75.5 (SD8.1), CHA2DS2-VASc 4.4 (SD1.4), HAS-BLED 3.8(SD0.9)] were included. Global success rate was 98.6%, successful LAAO with the first selected device size was achieved in 95.5% patients and the device was implanted at first attempt in 78.6% cases. There were only 9(2.5%) major peri-procedural complications. No differences in efficacy or safety results according to the centeŕs previous experience with Watchman 2.5 and procedural volume with Watchman FLX existed. Conclusions: The Watchman FLX attains high procedural success rates with complete LAA sealing in unselected, real-world patients, along with a low incidence of peri-procedural complications, regardless of operatoŕs experience with its previous device iteration or the number of Watchman FLX devices implanted