Continuous-flow left ventricular assist systems increase the rate of survival among patients with advanced heart failure but are associated with the development of pump thrombosis. We investigated ...the effects of a new magnetically levitated centrifugal continuous-flow pump that was engineered to avert thrombosis.
We randomly assigned patients with advanced heart failure to receive either the new centrifugal continuous-flow pump or a commercially available axial continuous-flow pump. Patients could be enrolled irrespective of the intended goal of pump support (bridge to transplantation or destination therapy). The primary end point was a composite of survival free of disabling stroke (with disabling stroke indicated by a modified Rankin score >3; scores range from 0 to 6, with higher scores indicating more severe disability) or survival free of reoperation to replace or remove the device at 6 months after implantation. The trial was powered for noninferiority testing of the primary end point (noninferiority margin, -10 percentage points).
Of 294 patients, 152 were assigned to the centrifugal-flow pump group and 142 to the axial-flow pump group. In the intention-to-treat population, the primary end point occurred in 131 patients (86.2%) in the centrifugal-flow pump group and in 109 (76.8%) in the axial-flow pump group (absolute difference, 9.4 percentage points; 95% lower confidence boundary, -2.1 P<0.001 for noninferiority; hazard ratio, 0.55; 95% confidence interval CI, 0.32 to 0.95 two-tailed P=0.04 for superiority). There were no significant between-group differences in the rates of death or disabling stroke, but reoperation for pump malfunction was less frequent in the centrifugal-flow pump group than in the axial-flow pump group (1 0.7% vs. 11 7.7%; hazard ratio, 0.08; 95% CI, 0.01 to 0.60; P=0.002). Suspected or confirmed pump thrombosis occurred in no patients in the centrifugal-flow pump group and in 14 patients (10.1%) in the axial-flow pump group.
Among patients with advanced heart failure, implantation of a fully magnetically levitated centrifugal-flow pump was associated with better outcomes at 6 months than was implantation of an axial-flow pump, primarily because of the lower rate of reoperation for pump malfunction. (Funded by St. Jude Medical; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755 .).
Microplastics have been a global concern due to their potential and widespread risks to organisms and environments. In this study, we investigated the abundance, distribution, and characteristics of ...microplastics (MPs) in the surface waters of the Bahía Blanca Estuary (BBE), specifically in its inner and middle zone. The results showed the dominant shape of MPs were fibers, being black, transparent, and blue the main colors. The concentrations of MPs ranged from 182 to 33,373 items m–3 with a mean value of 6162 items m–3. The highest concentrations of MPs were detected in the middle zone of the estuary, a site that receives untreated sewage effluents from the city. The most abundant size ranges were from 0.5 to 1.5 mm (44.21%) and ˂0.5 mm (40.21%) and were predominant at all the sampling sites. The concentration of mesoplastics in the inner zone (16 items m–3) presented larger values than in the middle zone (5 items m–3). A wide variety of polymeric materials with predominance of microfibers such as cellulose-based, polyacrylonitrile, polyethylene terephthalate, and polypropylene were identified. Polyester/alkyd resins and poli(vinyl chloride) were also found. The analysis of MPs surface through SEM/EDX detected a variety of elements such as C, O, Si, Al, K, Ca, Cl, Ti, Fe, S, and P, indicating potential contaminant carriers in the water column. Some plastic particles presented a high degree of degradation on their surface morphology. Untreated sewage discharges appear to be a significant input of MPs. Therefore, the results provided in the present study should be considered by stakeholders interested in the management and conservation of this large coastal wetland with significant ecological and economic value.
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•A mean of 6162 items m-3 was found in the surface waters of the estuary.•Cellulose, polyacrylonitrile, and polyesters were the most common polymers.•Mesoplastics (˃5 mm) were more abundant in the inner part of the estuary.•Black and transparent microplastics were the most conspicuous.•Sewage waters seemed to be the main input source of microplastics pollution.
Basalt reinforced composites are recently developed materials. These mineral amorphous fibres are a valid alternative to carbon fibres for their lower cost, and to glass fibres for their strength. In ...order to use basalt reinforced composites for structural applications, it is necessary to perform a mechanical characterisation. With this aim in the present work experimental results of several static and fatigue tests are described. Two polymeric matrices are taken into account, vinylester and epoxy, to assess their influence on the evaluated parameters. In parallel to these mechanical tests, also the thermal answer of the specimens to mechanical loads is evaluated by means of thermography. This experimental technique allows defining the composite local heating during the application of mechanical loads and its behaviour in details. Final discussion on obtained results is proposed focussing the attention on basalt fibre composite behaviour, and comparing mechanical properties of BFRP with other composite materials in glass and carbon fibres.
Microplastics (plastics <5 mm) contamination is of worldwide concern and represents a threat to the environment, biota, and humans. Also, they are potential carriers of other contaminants, increasing ...their adverse effects. In this study, it was analyzed for the first time the chemical composition and abundance of microplastics (MPs) in the commercial shrimp Pleoticus muelleri. Fibers were the predominant plastics (mean: 1.31 fibers g−1 wet weight) in the abdominal muscle of the shrimps being black, the dominant colour. μ-Raman showed that fibers were composed of polyethylene (PE), polypropylene (PP), and cellulose. Also, weathering and topography of the fibers were analyzed through wide-field confocal microscopy. C, O, Si, Al, K, as well as Fe, Zn, S, Ba, Br, and Ti on the plastic surface were detected with SEM/EDS, indicating potential carriers of contaminants.
The shrimp Pleoticusmuelleri ingests fibers with different chemical elements adsorbed on the plastic surface.
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•First study of the chemical characterization of microplastics in Pleoticus muelleri•Shrimps ingest mainly synthetic fibers.•Ba, Br, Zn, and Fe found in the MPs, could outline a potential health concern.•MPs in the edible part of the shrimps may be transferred to humans.
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•Local indigenous communities are exposed to toxic metals from mining activities.•Resuspension from the dry tailings could be transported up to 50 km in distance towards neighbouring ...villages.•Settled dust concentrations present high enrichment factors when compared with regional background values.•Children exposed to elevated metal concentrations might be at risk of non-carcinogenic and carcinogenic diseases.
Indigenous communities from northern Chile have historically been exposed to the impacts of massive copper industrial activities conducted in the region. Some of the communities belonging to the Alto El Loa Indigenous Development Area are located less than 10 km from the “Talabre'' tailings dam, which contains residues from copper production and other metals that can be toxic to human health (e.g., As, Sb, Cd, Mo, Pb). Given the increasing demand of copper production to achieve net-zero emission scenarios and concomitant expansions of the tailings, the exposure to toxic metals is a latent risk to local communities. Despite the impact that copper production could generate on ancestral communities from northern Chile, studies and monitoring are limited and the results are often not made accessible for local communities. Here, we evaluate such risks by characterizing metal concentrations in dust collected from roofs and windows of houses from the Alto El Loa area. Our results showed that As, Sb, Cd, Cu, Mo, Ag, S, and Pb concentrations in these matrices can be connected to local copper mining activities. Additionally, air transport models indicate that high concentrations of toxic elements (As, Sb, and Cd) can be explained by the atmospheric transport of particles from the tailings in a NE direction up to 50 km away. Pollution indices and Health Risk Assessment suggested a highly contaminated region with a health risk for its inhabitants. Our analysis on a local scale seeks to make visible the case of northern Chile as a critical territory where actions should be taken to mitigate the effects of mining in the face of this new scenario of international demand for the raw materials necessary for the transition to a net-zero carbon global society.
Heart failure leads to mitochondrial dysfunction and metabolic abnormalities of the failing myocardium coupled with an energy-depleted state and cardiac remodeling. The mitochondrial deacetylase ...sirtuin 3 (SIRT3) plays a pivotal role in the maintenance of mitochondrial function through regulating the mitochondrial acetylome. It is interesting to note that unique cardiac and systemic microRNAs have been shown to play an important role in cardiac remodeling by modulating key signaling elements in the myocardium.
Cellular signaling was analyzed in human cardiomyocyte-like AC16 cells, and acetylation levels in rodent models of SIRT3
and transgenic microRNA-195 (miR-195) overexpression were compared with wild type. Luciferase assays, Western blotting, immunoprecipitation assays, and echocardiographic analysis were performed. Enzymatic activities of pyruvate dehydrogenase (PDH) and ATP synthase were measured.
In failing human myocardium, we observed induction of miR-195 along with decreased expression of the mitochondrial deacetylase SIRT3 that was associated with increased global protein acetylation. We further investigated the role of miR-195 in SIRT3-mediated metabolic processes and its impact on regulating enzymes involved in deacetylation. Proteomic analysis of the total acetylome showed increased overall acetylation, and specific lysine acetylation of 2 central mitochondrial metabolic enzymes, PDH and ATP synthase, as well. miR-195 downregulates SIRT3 expression through direct 3'-untranslated region targeting. Treatments with either sirtuin inhibitor nicotinamide, small interfering RNA-mediated SIRT3 knockdown or miR-195 overexpression enhanced acetylation of PDH complex and ATP synthase. This effect diminished PDH and ATP synthase activity and impaired mitochondrial respiration.SIRT3
and miR-195 transgenic mice consistently showed enhanced global protein acetylation, including PDH complex and ATP synthase, associated with decreased enzymatic activity.
Altogether, these data suggest that increased levels of miR-195 in failing myocardium regulate a novel pathway that involves direct SIRT3 suppression and enzymatic inhibition via increased acetylation of PDH and ATP synthase that are essential for cardiac energy metabolism.
ABSTRACT
In this paper, we present the results of a spectroscopic campaign devoted to ascertaining the actual nature of a sample of five objects reported as chemically peculiar stars in the Catalogue ...of Ap, HgMn and Am stars (2009, A&A, 498, 961). Spectroscopic observations were obtained with Catania Astrophysical Observatory Spectropolarimeter. For each of the objects, we derive the effective temperature, gravity, rotational and radial velocities, and chemical abundances using the spectral synthesis method. All the targets were found to be SB1 systems. Our abundance analysis led us to classify HD 40788 and HD 187959 as marginal Am stars and HD 202431 as an Am star, and to confirm HD 134793 as an SrEuCr Ap star and, finally, HD 189652 as a normal star. Finally, we confirm that Am stars can possibly be used as an accurate tool to date stellar populations in galaxies.
Cystic fibrosis is a life-limiting disease that is caused by defective or deficient cystic fibrosis transmembrane conductance regulator (CFTR) protein activity. Phe508del is the most common CFTR ...mutation.
We conducted two phase 3, randomized, double-blind, placebo-controlled studies that were designed to assess the effects of lumacaftor (VX-809), a CFTR corrector, in combination with ivacaftor (VX-770), a CFTR potentiator, in patients 12 years of age or older who had cystic fibrosis and were homozygous for the Phe508del CFTR mutation. In both studies, patients were randomly assigned to receive either lumacaftor (600 mg once daily or 400 mg every 12 hours) in combination with ivacaftor (250 mg every 12 hours) or matched placebo for 24 weeks. The primary end point was the absolute change from baseline in the percentage of predicted forced expiratory volume in 1 second (FEV1) at week 24.
A total of 1108 patients underwent randomization and received study drug. The mean baseline FEV1 was 61% of the predicted value. In both studies, there were significant improvements in the primary end point in both lumacaftor-ivacaftor dose groups; the difference between active treatment and placebo with respect to the mean absolute improvement in the percentage of predicted FEV1 ranged from 2.6 to 4.0 percentage points (P<0.001), which corresponded to a mean relative treatment difference of 4.3 to 6.7% (P<0.001). Pooled analyses showed that the rate of pulmonary exacerbations was 30 to 39% lower in the lumacaftor-ivacaftor groups than in the placebo group; the rate of events leading to hospitalization or the use of intravenous antibiotics was lower in the lumacaftor-ivacaftor groups as well. The incidence of adverse events was generally similar in the lumacaftor-ivacaftor and placebo groups. The rate of discontinuation due to an adverse event was 4.2% among patients who received lumacaftor-ivacaftor versus 1.6% among those who received placebo.
These data show that lumacaftor in combination with ivacaftor provided a benefit for patients with cystic fibrosis homozygous for the Phe508del CFTR mutation. (Funded by Vertex Pharmaceuticals and others; TRAFFIC and TRANSPORT ClinicalTrials.gov numbers, NCT01807923 and NCT01807949.).
Trimethylamine-N-oxide (TMAO)-a gut-microbiota metabolite-is a biomarker of cardiometabolic risk. No studies have investigated TMAO as an early biomarker of longitudinal glucose increase or prevalent ...impaired glucose regulation. In a longitudinal cohort study, 300 diabetes-free men and women (77%) aged 20-55 years (mean = 34±10) were enrolled at baseline and re-examined at 2-years to investigate the association between TMAO and biomarkers of diabetes risk. Plasma TMAO was measured using Ultra Performance Liquid Chromatography-Mass Spectrometry. After an overnight fast, FPG was measured longitudinally, HbA1C and insulin were measured only at baseline. Insulin resistance was defined using HOMA-IR. Multivariable generalized linear models regressed; i) FPG change (year 2 minus baseline) on baseline TMAO tertiles; and ii) HOMA-IR and HbA1c on TMAO tertiles. Multivariable relative risk regressions modeled prevalent prediabetes across TMAO tertiles. Mean values of 2-year longitudinal FPG±SE across tertiles of TMAO were 86.6±0.9, 86.7±0.9, 86.4±0.9 (p = 0.98). Trends were null for FPG, HbA1c, HOMA-IR, cross-sectionally. The prevalence ratio of prediabetes among participants in 2nd and 3rd TMAO tertiles (vs. the 1st) were 1.94 95%CI 1.09-3.48 and 1.41 95%CI: 0.76-2.61. TMAO levels are associated with increased prevalence of prediabetes in a nonlinear fashion but not with insulin resistance or longitudinal FPG change.
Primary graft dysfunction (PGD) is one of the most common causes of early death after orthotopic heart transplantation. Mechanical circulatory support devices are required for severe forms of PGD. ...Venoarterial extracorporeal membrane oxygenation (VA-ECMO) and temporary ventricular assist device (VAD) support have both been reported to be useful for severe PGD.
Between January 2007 and December 2015, 597 patients received a heart transplant at our center. Of those, severe PGD developed in 44 patients (7.4%), and they received a continuous-flow external VAD (n = 17) or VA-ECMO (n = 27) support within 24 hours after transplant. We compared early and late outcomes between groups.
Baseline characteristics were similar between groups. Implantation of the temporary VAD required longer cardiopulmonary bypass time compared with VA-ECMO (323 ± 86 minutes vs 216 ± 65 minutes, p < 0.0001). Patients who received a VAD were more likely to have longer support time (14 ± 17 days vs 5.2 ± 3.9 days, p = 0.011), a higher incidence of major bleeding requiring chest reexploration (77% vs 30%, p = 0.0047), and a higher incidence of renal failure requiring renal replacement therapy (53% vs 11%, p = 0.0045) after surgery. Overall hospital mortality was 27%. In-hospital mortality for VAD and VA-ECMO patients were 41% and 19%, respectively (p = 0.16). Ten patients (59%) were weaned from VAD support, and 24 (89%) were weaned from VA-ECMO support after adequate graft function recovery (p = 0.03). The 3-year post-transplant survival was 41% in the VAD group and 66% in the VA-ECMO group (p = 0.13).
For severe PGD, support with VA-ECMO appears to result in better clinical outcomes compared with VAD.
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