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Emerging evidence from randomized clinical trials (RCTs) comparing distal radial access (DRA) with conventional radial access (RA) is available. The aim of this study was to provide a quantitative appraisal of the effects of DRA) vs conventional RA for coronary angiography with or without intervention. The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for RCT comparing DRA vs conventional RA for coronary angiography and/or intervention. Data were pooled by meta-analysis using a random-effects model. The primary endpoint was radial artery occlusion (RAO) at the longest available follow-up. Fourteen studies enrolling 6,208 participants were included. Compared with conventional RA, DRA was associated with a significant lower risk of RAO, either detected at latest follow-up (risk ratio [RR]: 0.36; 95% CI: 0.23-0.56; P < 0.001; number needed to treat [NNT] = 30) or in-hospital (RR: 0.32; 95% CI: 0.19-0.53; P < 0.001; NNT = 28), as well as EASY (Early Discharge After Transradial Stenting of Coronary Arteries) ≥II hematoma (RR: 0.51; 95% CI: 0.27-0.96; P = 0.04; NNT = 107). By contrast, DRA was associated with a higher risk of access site crossover (RR: 3.08; 95% CI: 1.88-5.06; P < 0.001; NNT = 12), a longer time for radial puncture (standardized mean difference [SMD]: 3.56; 95% CI: 0.96-6.16; P < 0.001), a longer time for sheath insertion (SMD: 0.37; 95% CI: 0.16-0.58; P < 0.001), and a higher number of puncture attempts (SMD: 0.59, 95% CI: 0.48-0.69; P < 0.001). Compared with conventional RA, DRA is associated with lower risks of RAO and EASY ≥II hematoma but requires longer time for radial artery cannulation and sheath insertion, more puncture attempts, and a higher access site crossover. [Display omitted] [ABSTRACT FROM AUTHOR]

Little is known about the safety and clinical utility of retrograde autologous priming (RAP) in patients undergoing minimally invasive mitral valve surgery. The study authors hypothesized that RAP would increase the oxygen delivery index (DO2i) while decreasing red blood cell transfusion requirements compared to valve surgery without RAP. The study was an observational analysis. A single institutional study. The authors analyzed data from 500 consecutive patients who underwent minimally invasive isolated mitral valve repair from December 31, 2012, to December 31, 2019. RAP was performed in 235 patients (47%) prior to the initiation of cardiopulmonary bypass (CPB). A continuous monitoring system was used for DO2 management during CPB. The mean arterial pressure was maintained between 55 and 70 mmHg, and the cardiac index was set at 2.4 L/min/m2, with adjustments in accordance with DO2i. The trigger point for red cell blood transfusion during CPB was hemoglobin <7 g/dL. Baseline hematocrit was lower in the RAP group compared to the no-RAP group (33.4 ± 3.6 v 38.1 ± 4.9, respectively; p < 0.001). Both CPB and cross-clamp times were similar between groups. Hematocrit during CPB was significantly higher in the RAP group compared to the no-RAP group (27.6 ± 2.6 v 25.9 ± 5.1, respectively; p < 0.001). RAP was also associated with significantly higher mean DO2i (292 ± 19.5 v 282.9 ± 35.1 mL/min/m2, respectively; p < 0.001) and fewer red blood cells transfusions during the intraoperative and immediate postoperative periods (p < 0.001). In a minimally invasive mitral valve context, RAP was safe and associated with better DO2i, higher hematocrit, and fewer intraoperative and postoperative red blood cell transfusions. [Display omitted] [ABSTRACT FROM AUTHOR]

Intraoperative temperature regimen usually is planned preoperatively by a "team." Selecting and understanding the impact of the temperature regimen (normothermia, or mild, moderate, or severe hypothermia) usually are related to the type of cardiac surgery (eg, using circulatory arrest or open-heart surgery). Cardiopulmonary bypass constitutes a challenging situation for monitoring temperature because of the rapid and extraordinary degree of heat transferred through the bypass circuit during heating and cooling. The core compartment undergoes the fastest temperature changes because of the rapid rate of blood reinfused into the organs. In modern cardiac surgery, different types and technologies of heater–cooler devices can be used in clinical practice, thanks to the development process that took its cue from past experiences. In this context, the authors review the role of thermal exchange in cardiac surgery and the progress achieved from first-to-second-generation heater–cooler devices. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is the most lethal gynecological cancer. OC cells have high proliferative capacity, are invasive, resist apoptosis, and tumors often display rearrangement of extracellular matrix (ECM) components, contributing to accelerated tumor progression. The multifunctional protein tissue transglutaminase (TG2) is known to be secreted in the tumor microenvironment, where it interacts with fibronectin (FN) and the cell surface receptor integrin β1. However, the mechanistic role of TG2 in cancer cell proliferation is unknown. Here, we demonstrate that TG2 directly interacts with and facilitates the phosphorylation and activation of the integrin effector protein integrin-linked kinase (ILK) at Ser246. We show that TG2 and p-Ser246-ILK form a complex that is detectable in patientderived OC primary cells grown on FN-coated slides. In addition, we show that coexpression of TGM2 and ILK correlates with poor clinical outcome. Mechanistically, we demonstrate that TG2-mediated ILK activation causes phosphorylation of glycogen synthase kinase-3α/β, allowing β-catenin nuclear translocation and transcriptional activity. Furthermore, inhibition of TG2 and ILK using small molecules, neutralizing antibodies, or shRNA-mediated knockdown blocks cell adhesion to the FN matrix, as well as the Wnt receptor response to the Wnt-3A ligand, and ultimately, cell adhesion, growth, and migration. In conclusion, we demonstrate that TG2 directly interacts with and activates ILK in OC cells and tumors and define a new mechanism that links ECM cues with β-catenin signaling in OC. These results suggest a central role of TG2-FN-integrin clusters in ECM rearrangement and indicate that downstream effector ILK may represent a potential new therapeutic target in OC. [ABSTRACT FROM AUTHOR]

Mycoplasma synoviae causes infectious synovitis and respiratory tract infections in chickens and is responsible for significant economic losses in the poultry industry. Effective attachment and colonisation of the trachea is critical for the persistence of the organism and progression of the disease it causes. The respiratory tract infection is usually sub-clinical, but concurrent infection with infectious bronchitis virus (IBV) is known to enhance the pathogenicity of M. synoviae. This study aimed to explore differentially expressed genes in the tracheal mucosa, and their functional categories, during chronic infection with M. synoviae , using a M. synoviae -IBV infection model. The transcriptional profiles of the trachea were assessed 2 weeks after infection using RNA sequencing. In chickens infected with M. synoviae or IBV, only 1 or 8 genes were differentially expressed compared to uninfected chickens, respectively. In contrast, the M. synoviae -IBV infected chickens had 621 upregulated and 206 downregulated genes compared to uninfected chickens. Upregulated genes and their functional categories were suggestive of uncontrolled lymphoid cell proliferation and an ongoing pro-inflammatory response. Genes associated with anti-inflammatory effects, pathogen removal, apoptosis, regulation of the immune response, airway homoeostasis, cell adhesion and tissue regeneration were downregulated. Overall, transcriptional changes in the trachea, 2 weeks after infection with M. synoviae and IBV, indicate immune dysregulation, robust inflammation and a lack of cytotoxic damage during chronic infection. This model provides insights into the pathogenesis of chronic infection with M. synoviae. • Mycoplasma synoviae causes respiratory tract infections in chickens. • The tracheal response to infection with M. synoviae was assessed at 2 weeks post infection. • Transcriptional changes were indicative of uncontrolled lymphoid cell proliferation and robust inflammation. • This analysis provides insights into the pathogenesis of chronic infection with M. synoviae. [ABSTRACT FROM AUTHOR]

Several strategies are being pursued to overcome the alarming pandemics of obesity and type 2 diabetes (T2D). In recent years, duodenal mucosal resurfacing (DMR) has shown its potential to improve glycemic indices. Following animal studies, which demonstrated feasibility and safety, the procedure has been applied in two human studies. The DMR procedure has been considered feasible and safe in humans with a limited occurrence of complications and adverse events. Reductions in glycated haemoglobin, weight, fasting plasma glucose, and alanine transaminase have been proven at different follow-up time-points. The length of the ablation may induce different outcomes, having the patients with long duodenal segment ablated showed greater beneficial effects. The current evidence does not still prove the apparent insulin-sensitizing mechanism explaining the impact of the DMR procedure on hepatic glucose production. However, the initial findings have demonstrated a positive risk-benefit ratio and an effect on the treatment of metabolic diseases, such as T2D. Future studies should clarify the mechanisms underlying the positive effects and durability of the treatment using controlled trial conditions on larger number of patients. [ABSTRACT FROM AUTHOR]

Mycoplasma gallisepticum causes chronic respiratory disease in poultry. A novel vaccine, Vaxsafe MG304 (the ts-304 strain), has greater protective efficacy in chickens than the Vaxsafe MG (strain ts-11) vaccine when delivered by eye drop at 3 weeks of age. Applying this vaccine in the hatchery to 1-day-old birds, using mass administration methods, would improve animal welfare and reduce labour costs associated with handling individual birds. This study assessed the protection provided by vaccination with Vaxsafe MG304 after administration to 1-day-old chicks. Chicks were administered a single dose of the vaccine to assess the efficacy of either a high dose (107.0 colour changing units, CCU) or a low dose (105.7 CCU) after eye drop or spray (in water or gel) administration against experimental challenge with virulent M. gallisepticum strain Ap3AS at 7 weeks of age. The vaccine was able to colonise the palatine cleft of chicks after vaccination by eye drop (at both doses) or by spray (in water or gel) (at the high dose). The high dose of vaccine, when delivered by eye drop or spray, was shown to be safe and induced a serological response and protective immunity (as measured by tracheal mucosal thickness and air sac lesion scores) against challenge. Vaccination of 1-day-old chicks with Vaxsafe MG304 by eye drop induced protective immunity equivalent to vaccination at 3 weeks of age. Vaxsafe MG304 was also protective when applied by both coarse- and gel spray methods at the higher dose and is therefore a suitable live attenuated vaccine for use in 1-day-old chicks. • Applying vaccines in the hatchery to 1-day-old birds would improve animal welfare and reduce costs associated with handling individual birds. • Vaccination with 107.0 CCU of Vaxsafe MG304 by eye drop or spray induced protective immunity against challenge. • This is the first study investigating a gel-based delivery method for the administration of a live attenuated mycoplasma vaccine. [ABSTRACT FROM AUTHOR]

Zinc Oxide (ZnO) nanoparticles are widely used both in the industry and in biomedical applications for their chemical and physical nanomaterial properties. It is therefore essential to go in depth into the cytotoxicity mechanisms and interactions between nanomaterials and cells. The aim of this work was to evaluate the dissolution of ZnO nanoparticles and their uptake, from a few minutes after treatments up to 24 h. ZnO nanoparticles routes of entry into the human colon carcinoma cells (LoVo) were followed at different times by a thorough ultrastructural investigation and semiquantitative analysis. The intracellular release of Zn 2 + ions by Zinquin fluorescent dye, and phosphorylated histone H2AX (γ-H2AX) expression were evaluated. The genotoxic potential of ZnO nanoparticles was also investigated by determining the levels of 8-hydroxyl-2′-deoxyguanosine (8-oxodG). The experimental data show that ZnO nanoparticles entered LoVo cells by either passive diffusion or endocytosis or both, depending on the agglomeration state of the nanomaterial. ZnO nanoparticles coming into contact with acid pH of lysosomes altered organelles structure, resulting in the release of Zn 2 + ions. The simultaneous presence of ZnO nanoparticles and Zn 2 + ions in the LoVo cells determined the formation of reactive oxygen species at the mitochondrial and nuclear level, inducing severe DNA damage. [ABSTRACT FROM AUTHOR]

Recent genetic studies have provided overwhelming evidence of the involvement of microglia-related molecular networks in the pathophysiology of Alzheimer’s disease (AD). However, the precise mechanisms by which microglia alter the course of AD neuropathology remain poorly understood. Here we discuss current evidence of the neuroprotective functions of microglia with a focus on optical imaging studies that have revealed a role of these cells in the encapsulation of amyloid deposits (“microglia barrier”). This barrier modulates the degree of plaque compaction, amyloid fibril surface area, and insulation from adjacent axons thereby reducing neurotoxicity. We discuss findings implicating genetic variants of the microglia receptor, triggering receptor expressed on myeloid cells 2, in the increased risk of late onset AD. We provide evidence that increased AD risk may be at least partly mediated by deficient microglia polarization toward amyloid deposits, resulting in ineffective plaque encapsulation and reduced plaque compaction, which is associated with worsened axonal pathology. Finally, we propose possible avenues for therapeutic targeting of plaque-associated microglia with the goal of enhancing the microglia barrier and potentially reducing disease progression. [ABSTRACT FROM AUTHOR]

Nowadays Fiber Reinforced Polymers (FRPs) represent a well-established technique for rehabilitation of Reinforced Concrete (RC) and masonry structures. However, the severe degradation of mechanical properties of FRP under high temperature and fire as well as poor sustainability represents major weak points of organic-based systems. The use of eco-friendly inorganic geopolymeric matrices, alternative to the polymeric resins, would be highly desirable to overcome these issues. The present work aims to investigate the bond characteristic of a novel Steel Reinforced Geopolymeric Matrix (SRGM) strengthening system externally bonded to a concrete substrate having low mechanical properties. SRGM composite material consists of stainless steel cords embedded into a fireproof geopolymeric matrix. Single-lap shear tests by varying the bonded length were carried out. The main failure mode observed of SRGM-concrete joints was debonding at the fiber-matrix interface. Test results also suggest the effective bond length. On the basis of the experimental results, a cohesive bond-slip law was proposed. [ABSTRACT FROM AUTHOR]

The paper presents an experimental and analytical study carried out on a set of Reinforced Concrete (RC) beams strengthened with a new eco-friendly composite material (Steel Reinforced Geopolymeric Matrix, SRGM) by using traditional Externally Bonded (EB) and innovative Inhibiting-Repairing-Strengthening (IRS) techniques. The proposed IRS solution is addressed to RC members with deteriorated cover concrete and/or corroded bars. It consists in the installation of a stainless steel fabric in the cover concrete, restoring this latter with an inorganic fireproof geopolymeric matrix which also acts as a corrosion inhibitor. The IRS solution reduces the time and then the costs of intervention with an environmentally friendly technology. It can be an effective alternative to EB technique. In order to simulate existing RC structures, two groups of large-scale RC beams were casted with low concrete strength and corroded smooth round/ribbed bars. Four RC beams were strengthened with IRS-SRGM/EB-SRGM systems and monotonically tested under four-point bending. Test results showed that the IRS-SRGM system provided greater load carrying capacity and ductility than the EB-SRGM system. Finally, a theoretical prediction of the tested beams, by means of a fracture mechanics based model, was carried out. The analytical/experimental comparisons are satisfactory. [ABSTRACT FROM AUTHOR]

The paper presents the results obtained from a numerical and analytical analysis carried out on a set of concrete beams reinforced with steel bars, Fiber Reinforced Polymer (FRP) bars and hybrid combinations of FRP-steel bars. To this purpose a database of experimental results, available in literature, was collected. A simple and reliable two-dimensional Finite Element (FE) model was defined. In the numerical simulations, the linear and nonlinear behavior of all materials was adequately modeled by appropriate constitutive laws. To simulate the concrete post-cracking tensile behavior a specific tension stiffening model was used. In order to overcome convergence difficulties, to simulate the quasi-static response of RC beams, a dynamic approach was adopted. Furthermore, to assess the effectiveness of the current Italian guideline, on same set of RC beams, an analytical analysis was performed. The comparisons between numerical/analytical results and experimental data highlighted the reliability of both the proposed FE model and the analytical model. The results show that the tension stiffening model used in the FE analysis provides good results with low and normal reinforcement ratios, whereas the numerical predictions are not acceptable with high reinforcement ratios. The analytical results provided by the Italian guideline are satisfactory, compared to experimental data. [ABSTRACT FROM AUTHOR]

Prophylactic use of antimicrobials after administration of live vaccines is a common practice in the poultry industry, but the impact of this on the efficacy and duration of protection induced by the vaccines is unknown. The effect of treatment with tylosin on the efficacy of vaccination with the live attenuated M. gallisepticum strain, Vaxsafe MG ts-304, was examined. This vaccine has previously been shown to provide protection for at least 57 weeks. Ten-week-old specific-pathogen-free chickens were vaccinated with Vaxsafe MG ts-304 and then treated with tylosin at a therapeutic dose in drinking water from 6 weeks after vaccination. Tylosin was withdrawn 5 days before challenge with M. gallisepticum strain Ap3AS at 6, 10, 14, 18 or 22 weeks after vaccination. Air sac lesions, tracheal mucosal thickening and the concentrations of serum antibodies against M. gallisepticum were assessed at 2 weeks after challenge. The protection induced by the vaccine in the 6 weeks before initiation of tylosin treatment persisted for 18 weeks after vaccination, with lesions only observed in the air sacs of vaccinated birds that had been treated with tylosin after challenge at 22 weeks after vaccination. Concentrations of serum antibodies against M. gallisepticum began to decrease in vaccinated birds that had been treated with tylosin from 16 weeks after vaccination. This study has suggested that treatment of chickens with tylosin after vaccination with a live attenuated mycoplasma vaccine reduces the duration of protective immunity afforded by the vaccine. • The impact of prophylactic antibiotic treatment on the efficacy and duration of protection induced by live bacterial vaccines in poultry was unknown. • The duration of immunity provided by the Vaxsafe MG ts-304 attenuated mycoplasma vaccine was shortened by treatment of chickens with tylosin. • Better understanding of the immunity offered by Vaxsafe MG ts-304 will assist in optimising its use, and thus control of mycoplasmosis, in the field. • Improving vaccinal control of mycoplasmas can reduce the use of antibiotics in poultry and thus improve public health. [ABSTRACT FROM AUTHOR]

The goal of the paper is to assess the effectiveness of some Fiber Reinforced Polymer (FRP)–concrete bond–slip laws, widely used in the numerical analyses, to model Steel Reinforced Grout (SRG)–concrete and/or Steel Reinforced Polymer (SRP)–concrete interfaces. The assessment was carried out through a suitable Finite Element (FE) study developed on a set of externally strengthened Reinforced Concrete (RC) beams. For this purpose a database of experimental results, available in literature, was collected. A two-dimensional FE model was defined for each tested beam. The linear and nonlinear behavior of all materials was adequately modeled, whereas the connection between concrete surface and external reinforcing layer was simulated by a cohesive element with a suitable damage model. The numerical and experimental comparisons were used to evaluate the reliability and adaptability of the FRP–concrete bond–slip laws to predict the structural behavior of RC beams externally strengthened to flexure with SRG and SRP innovative systems. The study showed that among a set of bi-linear FRP–concrete bond–slip laws one was also suitable to simulate the behavior of SRG–concrete interface. For the SRP–concrete interface a modification of the same bond–slip law was proposed, calibrated and validated against the available experimental data. [ABSTRACT FROM AUTHOR]

Previous investigations demonstrated that pretreatment with non-cytotoxic concentrations of voacamine had a chemosensitizing effect on cultured multidrug resistant osteosarcoma cells exposed to doxorubicin; whereas when used alone at high concentrations voacamine induced apoptosis-independent cell death on both sensitive and resistant cells. To gain insight into the mechanism of action of voacamine at the subcellular level, we developed an analytical high-performance thin-layer chromatography technique to assess the intracellular content of voacamine that could be correlated with the induction of cell death and consequent morphological and ultrastructural changes. The results of the quantitative analysis not only did allow us to measure both the amount of unmodified voacamine molecules (determined by the method) and the amount of molecules which reacted with cellular components (undetectable), but also to confirm the findings of our previous studies and support the validity of this method. [ABSTRACT FROM AUTHOR]

The KNOTTED-like transcription factors (KNOX) contribute to plant organ development. The expression patterns of peach KNOX genes showed that the class 1 members act precociously (S1–S2 stages) and differentially during drupe growth. Specifically, the transcription of KNOPE1 and 6 decreased from early (cell division) to late (cell expansion) S1 sub-stages, whilst that of STMlike1 , 2, KNOPE2 , 2.1 ceased at early S1. The KNOPE1 role in mesocarp was further addressed by studying the mRNA localization in the pulp cells and vascular net at early and late S1. The message signal was first diffuse in parenchymatous cells and then confined to hypodermal cell layers, showing that the gene down-tuning accompanied cell expansion. As for bundles, the mRNA mainly featured in the procambium/phloem of collateral open types and subsequently in the phloem side of complex structures (converging bundles, ducts). The KNOPE1 overexpression in Arabidopsis caused fruit shortening, decrease of mesocarp cell size, diminution of vascular lignification together with the repression of the major gibberellin synthesis genes AtGA20ox1 and AtGA3ox1 . Negative correlation between the expression of KNOPE1 and PpGA3ox1 was observed in four cultivars at S1, suggesting that the KNOPE1 repression of PpGA3ox1 may regulate mesocarp differentiation by acting on gibberellin homeostasis. [ABSTRACT FROM AUTHOR]

The paper presents a theoretical prediction of the structural behavior of reinforced concrete (RC) beams externally strengthened to flexure by using a unidirectional ultra-high tensile strength steel (UHTSS) reinforcing mesh embedded in an inorganic matrix (Steel Reinforced Grout, SRG) or in an organic matrix (Steel Reinforced Polymer, SRP). For these innovative composite materials are not yet available in literature specific standard documents, guidelines or analytical models capable to predict the structural behavior of the strengthened elements. Therefore, in order to evaluate the flexural strength of the strengthened beams some analytical models to predict the maximum axial strain developed in Fiber Reinforced Polymer (FRP) systems at the onset of intermediate debonding failure, have been used. The goal is to assess the effectiveness of current analytical models used, up to day, to FRP strengthening systems to the SRG and SRP strengthening systems. For this aim, a database of experimental results on RC beams strengthened in bending by bonded SRG and SRP systems has been collected. The comparisons between the theoretical predictions and the experimental data, in terms of debonding strain values, load carrying capacity, load-midspan deflection curves, have highlighted the reliability and adaptability of the current analytical models. Finally, in order to evaluate the effectiveness of the SRG and SRP systems for strengthening RC beams a parametric study was also carried out. [ABSTRACT FROM AUTHOR]