The term sepsis refers to a complex and heterogeneous syndrome. Although great progress has been made in improving the diagnosis and treatment of this condition, it continues to have a huge impact on ...morbidity and mortality worldwide. Mesenchymal stem cells are a population of multipotent cells that have immunomodulatory properties, anti-apoptotic effects, and antimicrobial activity. We studied these capacities in a porcine model of peritoneal sepsis.
We infused human adipose-derived mesenchymal stem cells (ADSCs) into a porcine model of peritoneal sepsis. Twenty piglets were treated with antibiotics alone (control group) or antibiotics plus peritoneal infusion of ADSCs at a concentration of 2 × 10
cells/kg or 4 × 10
cells/kg (low- and high-dose experimental groups, respectively). The animals were evaluated at different time points to determine their clinical status, biochemical and hematologic parameters, presence of inflammatory cytokines and chemokines in blood and peritoneal fluid, and finally by histologic analysis of the organs of the peritoneal cavity.
One day after sepsis induction, all animals presented peritonitis with bacterial infection as well as elevated C-reactive protein, haptoglobin, IL-1Ra, IL-6, and IL-1b. Xenogeneic ADSC infusion did not elicit an immune response, and peritoneal administration of the treatment was safe and feasible. One day after infusion, the two experimental groups showed a superior physical condition (e.g., mobility, feeding) and a significant increase of IL-10 and TGF-β in blood and a decrease of IL-1Ra, IL-1b, and IL-6. After 7 days, all animals treated with ADSCs had better results concerning blood biomarkers, and histopathological analysis revealed a lower degree of inflammatory cell infiltration of the organs of the peritoneal cavity.
Intraperitoneal administration of ADSCs as an adjuvant therapy for sepsis improves the outcome and diminishes the effects of peritonitis and associated organ damage by regulating the immune system and reducing intra-abdominal adhesions in a clinically relevant porcine model of abdominal sepsis.
Abstract
Rear‐edge tree populations are experiencing a combination of higher temperatures and more intense droughts that might push individuals beyond their tolerance limits. This trend towards ...rising atmospheric CO
2
is concurrent with an increase in intrinsic water use efficiency (iWUE), which theoretically enhances photosynthesis and decrease evapotranspiration rates, consequently improving tree resistance to drought. However, it remains unclear whether iWUE is favouring tree growth under current climate conditions, particularly when climate and iWUE legacy effects are simultaneously considered.
We evaluated this question with an extensive sampling along Iberian rear‐edge (dry) populations comprising four mountain ranges and two distinct altitudes. We simultaneously examined the effects of climate and iWUE on secondary growth using annually resolved basal area increments (BAIs) for the period 1901–2017. We used linear mixed models including second‐order autocorrelation and 1‐year legacy effects of iWUE and summer drought.
BAI and iWUE increased across the studied period. iWUE increase was driven by changes in atmospheric CO
2
concentration and water availability during the growing season. Climate and iWUE exerted direct and lagged effects on beech growth. Water availability during growing season was the main driver of tree growth, combining direct and indirect effects through its impact on iWUE. Legacy effects of water availability and iWUE were more important than growing season conditions. The net effect of iWUE shifted when lagged effects were considered, resulting in a net negative impact on tree growth.
Synthesis
: Our results reveal that climate and iWUE legacy effects must be considered to assess the net iWUE effect on secondary growth. Considering lagged effects, the current increase in iWUE is constraining tree growth. Modelling efforts of tree growth response to climate warming should include climate and iWUE legacy effects to adequately assess terrestrial ecosystem carbon balance.
Myelofibrosis (MF) occurs as part of the natural history of polycythemia vera (PV) and essential thrombocythemia (ET), and remarkably shortens survival. Although JAK2V617F and CALR allele burden are ...the main transformation risk factors, inflammation plays a critical role by driving clonal expansion toward end-stage disease. NF-κB is a key mediator of inflammation-induced carcinogenesis. Here, we explored the involvement of miR-146a, a brake in NF-κB signaling, in MPN susceptibility and progression. rs2910164 and rs2431697, that affect miR-146a expression, were analyzed in 967 MPN (320 PV/333 ET/314 MF) patients and 600 controls. We found that rs2431697 TT genotype was associated with MF, particularly with post-PV/ET MF (HR = 1.5; p < 0.05). Among 232 PV/ET patients (follow-up time=8.5 years), 18 (7.8%) progressed to MF, being MF-free-survival shorter for rs2431697 TT than CC + CT patients (p = 0.01). Multivariate analysis identified TT genotype as independent predictor of MF progression. In addition, TT (vs. CC + CT) patients showed increased plasma inflammatory cytokines. Finally, miR-146a
mice showed significantly higher Stat3 activity with aging, parallel to the development of the MF-like phenotype. In conclusion, we demonstrated that rs2431697 TT genotype is an early predictor of MF progression independent of the JAK2V617F allele burden. Low levels of miR-146a contribute to the MF phenotype by increasing Stat3 signaling.
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•xPt/TNT catalysts were synthesized for the vapor phase impregnation methodology.•The catalysts showed uniformly dispersed Pt particles supported on titania nanotubes (TNT).•A strong ...metal-support interaction between Pt and TNT support hinder Pt nanoparticles to agglomerate into larger particles, even at high Pt loadings.•xPt/TNT materials show a high catalytic activity in naphthalene hydrogenation.
A range of Pt loadings (0.9–21.5 wt. %) on titania nanotubes (TNT) catalysts were prepared with a view to address metal-support interaction effects on Pt nanoparticles (size, dispersion, shape) and were prepared by a vapor-phase impregnation method using Pt(acac). The reduced catalysts were characterized by XRD, TEM, H2-TPD, CO adsorption FTIR and examined as catalysts in naphthalene hydrogenation. Pt nanoparticles have a very uniform size between 1.4–2.2 nm for Pt loadings 0.9–21.5 wt% as indicated by TEM, H2-TPD and CO-adsorption FTIR. A strong metal-support interaction between Pt and TNT support hinder Pt nanoparticles to agglomerate into larger particles, even at high Pt loadings. Both Pt edge sites and exposed surface total Pt sites are highest at 10.2 wt.% Pt loading and parallels naphthalene hydrogenation activity which peaks at this loading.
Abstract Parkinson's disease (PD) is diagnosed when striatal dopamine (DA) loss exceeds a certain threshold and the cardinal motor features become apparent. The presymptomatic compensatory mechanisms ...underlying the lack of motor manifestations despite progressive striatal depletion are not well understood. Most animal models of PD involve the induction of a severe dopaminergic deficit in an acute manner, which departs from the typical, chronic evolution of PD in humans. We have used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administered to monkeys via a slow intoxication protocol to produce a more gradual development of nigral lesion. Twelve control and 38 MPTP-intoxicated monkeys were divided into four groups. The latter included monkeys who were always asymptomatic, monkeys who recovered after showing mild parkinsonian signs, and monkeys with stable, moderate and severe parkinsonism. We found a close correlation between cell loss in the substantia nigra pars compacta (SNc) and striatal dopaminergic depletion and the four motor states. There was an overall negative correlation between the degree of parkinsonism (Kurlan scale) and in vivo PET (18 F-DOPA Ki and11 C-DTBZ binding potential), as well as with TH-immunoreactive cell counts in SNc, striatal dopaminergic markers (TH, DAT and VMAT2) and striatal DA concentration. This intoxication protocol permits to establish a critical threshold of SNc cell loss and dopaminergic innervation distinguishing between the asymptomatic and symptomatic parkinsonian stages. Compensatory changes in nigrostriatal dopaminergic activity occurred in the recovered and parkinsonian monkeys when DA depletion was at least 88% of control, and accordingly may be considered too late to explain compensatory mechanisms in the early asymptomatic period. Our findings suggest the need for further exploration of the role of non-striatal mechanisms in PD prior to the development of motor features.
Breastfeeding is recognized worldwide as the best option for infant feeding. Expressing breast milk is an alternative for mothers to provide their infants all the benefits of maternal milk. During ...breast milk expression, mothers receive a distinct kind of sensory stimulation, because there is no direct bodily or affective interaction with their infants, many women report feeling isolated, generating a love-hate relation with pumping, and even low levels of satisfaction while expressing breast milk. While it is well known that the prefrontal, parietal, and temporal cortices play important roles in the emotional and cognitive processing of maternal stimuli, knowledge about how these cortical areas function during breastfeeding is lacking. This study was designed to characterize EEG activity in the prefrontal and parietal cortices and the affective scores of primiparous breastfeeding mothers during two conditions of milk expression: breast milk expression and direct breastfeeding. Participants reported higher valence and arousal and a pleasant state during direct breastfeeding. In the direct breastfeeding condition, both prefrontal areas showed a higher absolute power (AP) of the slow bands, with a lower AP of the alpha band in the parietal cortex. A lower correlation between frontopolar and dorsolateral areas with a higher correlation between prefrontal and parietal cortices was obtained mainly in the right hemisphere. This EEG activity could be linked to an internal state of focused attention and, simultaneously, open monitoring of the environment that suggests an integration of the motive-emotional and cognitive processes necessary for adequate mother-baby interaction during direct breastfeeding.
•During direct breastfeeding, prefrontal areas showed higher absolute power in the slow bands.•EEG activity during direct breastfeeding could be related to a motivational-cognitive state.•Direct breastfeeding is a pleasurable state for the mother.
Pseudomonas aeruginosa is one of the most worrisome infectious bacteria due to its intrinsic and acquired resistance against several antibiotics and the recalcitrance of its infections; hence, the ...development of novel antimicrobials effective against multidrug‐resistant P. aeruginosa is mandatory. In this work, silver nanoparticles obtained by green synthesis using a leaf extract and fungi were tested against a battery of clinical strains from cystic fibrosis, pneumonia and burnt patients, some of them with multidrug resistance. Both nanoparticles showed a potent antibacterial effect, causing severe damage to the cell wall, membrane and DNA, and inducing the production of reactive oxygen species. Moreover, the nanoparticles derived from fungi showed synergistic antibacterial effects with the antibiotics meropenem and levofloxacin for some clinical strains and both kinds of nanoparticles were nontoxic for larvae of the moth Galleria mellonella, encouraging further research for their implementation in the treatment of P. aeruginosa infections.
Significance and Impact of the Study: The continuous rise of antibiotic resistance in bacteria such as Pseudomonas aeruginosa is a serious threat to human health, hence it is mandatory to identify novel ways to combat its infections. In this work, silver nanoparticles were synthesized in a green way using leaves and fugal extracts and its antibacterial effects were tested against clinical strains. The nanoparticles killed the strains due severe cellular damage affecting the membranes, the DNA and generating reactive oxygen species, in addition they were nontoxic and displayed synergy with some antibiotics; therefore, being a promising alternative to treat MDR P. aeruginosa infections.
Abstract
Understanding the formation and evolution of our Galaxy requires accurate distances, ages, and chemistry for large populations of field stars. Here, we present several updates to our ...spectrophotometric distance code, which can now also be used to estimate ages, masses, and extinctions for individual stars. Given a set of measured spectrophotometric parameters, we calculate the posterior probability distribution over a given grid of stellar evolutionary models, using flexible Galactic stellar-population priors. The code (called StarHorse) can accommodate different observational data sets, prior options, partially missing data, and the inclusion of parallax information into the estimated probabilities. We validate the code using a variety of simulated stars as well as real stars with parameters determined from asteroseismology, eclipsing binaries, and isochrone fits to star clusters. Our main goal in this validation process is to test the applicability of the code to field stars with known Gaia-like parallaxes. The typical internal precisions (obtained from realistic simulations of an APOGEE+Gaia-like sample) are ${\simeq } 8\,\,\rm{per\,\,cent}$ in distance, ${\simeq } 20\,\,\rm{per\,\,cent}$ in age, ${\simeq } 6\,\,\rm{per\,\,cent}$ in mass, and ≃ 0.04 mag in AV. The median external precision (derived from comparisons with earlier work for real stars) varies with the sample used, but lies in the range of ${\simeq } 0,2\,\,\rm{per\,\,cent}$ for distances, ${\simeq } 12,31\,\,\rm{per\,\,cent}$ for ages, ${\simeq } 4,12\,\,\rm{per\,\,cent}$ for masses, and ≃ 0.07 mag for AV. We provide StarHorse distances and extinctions for the APOGEE DR14, RAVE DR5, GES DR3, and GALAH DR1 catalogues.
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•347 stainless steel plates were welded under electromagnetic field of low intensity.•Welding with 3 mT improves the resistance to localized corrosion in the HAZ.•The electromagnetic ...interaction reduces the grain size adjacent to the fusion line.•The improvement in corrosion resistance results from chemical homogenization of the γ matrix.
The electromagnetic interaction of low intensity (EMILI) induced by the application of external electromagnetic fields of low intensity (EMFLI) during fusion welding of AISI 347 stainless steel improved the resistance to intergranular corrosion (RIGC). Microstructural observations and electrochemical methods were used to determine the metallurgical condition related to the enhanced RIGC. EMILI reduced the degree of sensitization (DOS) at the heat affected zone (HAZ) as compared to plain welds. EMILI induced Cr redistribution in the γ-matrix during welding, reducing the formation of δ-ferrite and minimizing Cr depletion.
Using combined asteroseismic and spectroscopic observations of 418 red-giant stars close to the Galactic disc plane (6 kpc < RGal ≲ 13 kpc, | ZGal| < 0.3 kpc), we measure the age dependence of the ...radial metallicity distribution in the Milky Way’s thin disc over cosmic time. The slope of the radial iron gradient of the young red-giant population (−0.058 ± 0.008 stat. ±0.003 syst. dex/kpc) is consistent with recent Cepheid measurements. For stellar populations with ages of 1−4 Gyr the gradient is slightly steeper, at a value of −0.066 ± 0.007 ± 0.002 dex/kpc, and then flattens again to reach a value of ~−0.03 dex/kpc for stars with ages between 6 and 10 Gyr. Our results are in good agreement with a state-of-the-art chemo-dynamical Milky-Way model in which the evolution of the abundance gradient and its scatter can be entirely explained by a non-varying negative metallicity gradient in the interstellar medium, together with stellar radial heating and migration. We also offer an explanation for why intermediate-age open clusters in the solar neighbourhood can be more metal-rich, and why their radial metallicity gradient seems to be much steeper than that of the youngest clusters. Already within 2 Gyr, radial mixing can bring metal-rich clusters from the innermost regions of the disc to Galactocentric radii of 5 to 8 kpc. We suggest that these outward-migrating clusters may be less prone to tidal disruption and therefore steepen the local intermediate-age cluster metallicity gradient. Our scenario also explains why the strong steepening of the local iron gradient with age is not seen in field stars. In the near future, asteroseismic data from the K2 mission will allow for improved statistics and a better coverage of the inner-disc regions, thereby providing tighter constraints on theevolution of the central parts of the Milky Way.
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