Meldgaardleblanc0757

INTRODUCTION Survivors of extreme prematurity may have disrupted lung development. We hypothesized that the multiple breath washout (MBW) index Scond, which is intended to reflect ventilation inhomogeneity from the conducting airways, could be a sensitive marker of respiratory impairment in this group. METHODS Spirometry, TLco, and MBW were cross-sectionally evaluated at 8 to 14 years of age in children born at less then 28 weeks between 2004 and 2010 in Udine, Italy. Age-matched controls born at term were also included. Bronchopulmonary dysplasia (BPD) was defined as oxygen-dependence at 36 weeks postmenstrual age. The limits of normal were the 5th percentile of the reference population (Global Lung Initiative) for spirometry and TLco and the 95th percentile of controls for Lung Clearance Index, Scond, and Sacin from MBW. RESULTS Results were obtained in 47 extremely preterm children (53% boys, mean ± standard deviation age 11.3 ± 2.0 years, 40% with BPD) and 60 controls (50% boys, 11.6 ± 1.9 years). There were significant differences between preterm children and controls in all lung function outcomes, except for Sacin. Among children born less then 28 weeks, Scond tended to be frequently abnormal than FEV1 z-score (29% vs 14%, P = .06). At multivariable linear regression, in the preterm group, current asthma was significantly associated with a higher Scond (B = 0.019, 95% confidence interval, 0.000-0.038), whereas BPD was not. CONCLUSION Almost a third of extremely preterm children at school age showed Scond alterations that affected also children without BPD. Longitudinal studies should clarify the prognostic meaning of Scond abnormalities in this group. © 2020 Wiley Periodicals, Inc.AIMS Heart failure with mid-range ejection fraction (HFmrEF) has been proposed as a distinct HF phenotype, but whether patients on this category fare worse, similarly, or better than those with HF with reduced EF (HFrEF) or preserved EF (HFpEF) in terms of rehospitalization risks over time remains unclear. METHODS AND RESULTS We prospectively included 2961 consecutive patients admitted for acute HF (AHF) in our institution. Of them, 158 patients died during the index admission, leaving the sample size to be 2803 patients. Patients were categorized according to their EF HFrEF if EF ≤ 40% (n = 908, 32.4%); HFmrEF if EF = 41-49% (n = 449, 16.0%); and HFpEF if EF ≥ 50% (n = 1446, 51.6%). Covariate-adjusted incidence rate ratios (IRRs) were used to evaluate the association between EF status and recurrent all-cause and HF-related admissions. At a median follow-up of 2.6 years (inter-quartile range 1.0-5.3), 1663 (59.3%) patients died, and 6035 all-cause readmissions were registered in 2026 patients (72.3%), 2163 of them HF related. Rates of all-cause readmission per 100 patients-years of follow-up were 150.1, 176.9, and 163.6 in HFrEF, HFmrEF, and HFpEF, respectively (P = 0.097). After multivariable adjustment, when compared with that of patients with HFrEF and HFpEF, HFmrEF status was not significantly associated with a different risk of all-cause readmissions (IRR = 0.99; 95% confidence interval [CI], 0.77-1.27; P = 0.926; and IRR = 0.93; 95% CI, 0.74-1.18; P = 0.621, respectively) or HF-related readmissions (IRR = 1.06; 95% CI, 0.77-1.46; P = 0.725; and IRR = 1.11; 95% CI, 0.82-1.50; P = 0.511, respectively). CONCLUSIONS Following an admission for AHF, patients with HFmrEF had a similar rehospitalization burden and a similar risk of recurrent all-cause and HF-related admissions than had patients with HFrEF or HFpEF. Regarding morbidity risk, HFmrEF seems not to be a distinct HF phenotype. © 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.AIMS Non-compaction cardiomyopathy (NCM) is a congenital heart disease characterized by an arrest of the myocardial compaction process. Although NCM patients have impaired formation of microvasculature, the functional impact of these changes remains undefined. We sought to analyse a potential correlation between myocardial ischemia and heart failure severity in NCM patients. METHODS AND RESULTS We enrolled 41 NCM patients (28 male and 13 female), aged 21-70 years. In all patients, we have determined left ventricular end-diastolic volume (LVEDV), left ventricular ejection fraction (LVEF), and global longitudinal strain (GLS) by echocardiography. At the same time, serum levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been measured, and myocardial single-photon emission computed tomography at rest and on stress was used to define significant myocardial ischemia defined as summed difference score ≥ 2. Myocardial ischemia has been demonstrated in 11 patients (27%, Group A), and 30 patients showed no significant ischemic changes (73%, Group B). The groups did not differ in sex, age, kidney, or liver function. When compared with Group B, Group A had significantly lower LVEF (35 ± 15% in Group A vs. 53 ± 11% in Group B, P less then 0.001), higher LVEDV (188 ± 52 mL vs. 136 ± 52 mL, P = 0.007), lower GLS (-9.9 ± 5.2% vs. -14.5 ± 4.1%, P = 0.001), and higher NT-proBNP levels (1691 ± 1883 pg/mL vs. 422 ± 877 pg/mL, P = 0.006). Overall, higher summed difference score was associated with lower LVEF (r = -0.48, P = 0.001), higher LVEDV (r = 0.39, P = 0.012), lower GLS (r = 0.352, P = 0.024), and higher levels of NT-proBNP (r = 0.66, P less then 0.001). CONCLUSIONS The presence of myocardial ischemia in patients with NCM is associated with worse left ventricular function, dilation of the left ventricle, and more pronounced neurohumoral activation. © 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.Filamentous fungi are important cell factories for large-scale enzyme production. However, production levels are often low, and this limitation has stimulated research focusing on the manipulation of genes with predicted function in the protein secretory pathway. This pathway is the major route for the delivery of proteins to the cell exterior, and a positive relationship between the production of recombinant enzymes and the unfolded protein response (UPR) pathway has been observed. In this study, Aspergillus nidulans was exposed to UPR-inducing chemicals and differentially expressed genes were identified by RNA-seq. Twelve target genes were deleted in A. read more nidulans recombinant strains producing homologous and heterologous GH10 xylanases. The knockout of pbnA (glycosyltransferase), ydjA (Hsp40 co-chaperone), trxA (thioredoxin) and cypA (cyclophilin) improved the production of the homologous xylanase by 78, 171, 105 and 125% respectively. Interestingly, these deletions decreased the overall protein secretion, suggesting that the production of the homologous xylanase was specifically altered. However, the production of the heterologous xylanase and the secretion of total proteins were not altered by deleting the same genes. Considering the results, this approach demonstrated the possibility of rationally increase the production of a homologous enzyme, indicating that trxA, cypA, ydjA and pbnA are involved in protein production by A. nidulans. © 2020 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.This study develops a computational model of the braided stent for interpreting the mechanism of stent flattening during deployment into curved arteries. Stent wires are expressed using Kirchhoff's rod theory and their mechanical behavior is treated using a corotational beam formulation. The equation of motion of the braided stent is solved in a step-by-step manner using the resultant elastic force and mechanical interactions of wires with friction. Examples of braided-stent deployment into idealized arteries with various curvatures are numerically simulated. In cases of low curvature, the braided stent expands from a catheter by releasing the bending energy stored in stent wires, while incomplete expansion is found at both stent ends (ie, the fish-mouth phenomenon), where relatively little bending energy is stored. In cases of high curvature, much torsional energy is stored in stent wires locally in the midsection of the curvature and the bending energy for stent self-expansion is not fully released even after deployment, leading to stent flattening. These findings suggest that the mechanical state of the braided stent and its transition during deployment play an important role in the underlying mechanism of stent flattening. NOVELTY STATEMENT This study developed a computational mechanical model of the braided stent for interpreting stent flattening, which is a critical issue observed during deployment into highly curved arteries. Mechanical behaviors of the stent wires are appropriately treated by corotational beam element formulation with considering multiple contacts. We conducted numerical examples of the stent deployment into curved arteries and found that the mechanical state of the braided stent during deployment associated with occurrences of the stent flattening. We believe this finding gives new insight into the mechanism of stent flattening and would advance the design of the stent and its deployment protocol. © 2020 John Wiley & Sons, Ltd.In this review, we focus on the phenomenon of chimerism and especially microchimerism as one of the currently underexplored explanations for differences in health and behavior. Chimerism is an amalgamation of cells from two or more unique zygotes within a single organism, with microchimerism defined by a minor cell population of less then 1%. This article first presents an overview of the primary techniques employed to detect and quantify the presence of microchimerism and then reviews empirical studies of chimerism in mammals including primates and humans. In women, male microchimerism, a condition suggested to be the result of fetomaternal exchange in utero, is relatively easily detected by polymerase chain reaction molecular techniques targeting Y-chromosomal markers. Consequently, studies of chimerism in human diseases have largely focused on diseases with a predilection for females including autoimmune diseases, and female cancers. We detail studies of chimerism in human diseases and also discuss some potential implications in behavior. Understanding the prevalence of chimerism and the associated health outcomes will provide invaluable knowledge of human biology and guide novel approaches for treating diseases. © 2020 Wiley Periodicals, Inc.This study presents a simulation-based methodology to design porous stents to induce suitable hemodynamic environments inside Abdominal Aortic Aneurysm (AAA) sacs. In the proposed methodology, an optimization algorithm iteratively modifies the porosity distribution of the stent, and executes a computational fluid dynamics (CFD) simulation to determine the effect of these changes on the hemodynamic conditions inside the aneurysm sac. The optimization iterations proceed until relevant hemodynamic parameters are within ranges prescribed a priori by the user as desirable to control the progression of the AAA. The resulting porosity distribution uniquely describes the porous stent design that can control the hemodynamic environment (e.g., shear stress at the aneurysm wall, pressure distribution, residence time), reducing AAA rupture risks and improving treatment efficacy. To demonstrate its potential, the proposed methodology is applied to idealized AAA geometry under steady-state flow conditions, though it may be easily applied to more complex AAA geometries under transient, pulsatile flow conditions.