Mesenchymal stem cells (MSC) are present in all organs and tissues. Several studies have shown the therapeutic potential effect of MSC or their derived products. However, the functional heterogeneity ...of MSC constitutes an important barrier for transferring these capabilities to the clinic. MSC heterogeneity depends on their origin (biological niche) or the conditions of potential donors (age, diseases or unknown factors). It is accepted that many culture conditions of the artificial niche to which they are subjected, such as O
2
tension, substrate and extracellular matrix cues, inflammatory stimuli or genetic manipulations can influence their resulting phenotype. Therefore, to attain a more personalized and precise medicine, a correct selection of MSC is mandatory, based on their functional potential, as well as the need to integrate all the existing information to achieve an optimal improvement of MSC features in the artificial niche.
•The vitamin D endocrine system have a variety of actions on cells and tissues involved in COVID-19 progression.•Early calcifediol (25-hydroxyvitamin D) treatment to hospitalized COVID-19 patients ...significantly reduced intensive care unit admissions-Calcifediol seems to be able to reduce severity of the COVID-19.•Calcifediol seems to be able to reduce severity of the disease.
The vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID-19 progression especially by decreasing the Acute Respiratory Distress Syndrome. Calcifediol can rapidly increase serum 25OHD concentration. We therefore evaluated the effect of calcifediol treatment, on Intensive Care Unit Admission and Mortality rate among Spanish patients hospitalized for COVID-19.
Parallel pilot randomized open label, double-masked clinical trial.
University hospital setting (Reina Sofia University Hospital, Córdoba Spain.)
76 consecutive patients hospitalized with COVID-19 infection, clinical picture of acute respiratory infection, confirmed by a radiographic pattern of viral pneumonia and by a positive SARS-CoV-2 PCR with CURB65 severity scale (recommending hospital admission in case of total score > 1).
All hospitalized patients received as best available therapy the same standard care, (per hospital protocol), of a combination of hydroxychloroquine (400 mg every 12 h on the first day, and 200 mg every 12 h for the following 5 days), azithromycin (500 mg orally for 5 days. Eligible patients were allocated at a 2 calcifediol:1 no calcifediol ratio through electronic randomization on the day of admission to take oral calcifediol (0.532 mg), or not. Patients in the calcifediol treatment group continued with oral calcifediol (0.266 mg) on day 3 and 7, and then weekly until discharge or ICU admission. Outcomes of effectiveness included rate of ICU admission and deaths.
Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50 %) p value X2 Fischer test p < 0.001. Univariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment versus without Calcifediol treatment: 0.02 (95 %CI 0.002−0.17). Multivariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment vs Without Calcifediol treatment ICU (adjusting by Hypertension and T2DM): 0.03 (95 %CI: 0.003-0.25). Of the patients treated with calcifediol, none died, and all were discharged, without complications. The 13 patients not treated with calcifediol, who were not admitted to the ICU, were discharged. Of the 13 patients admitted to the ICU, two died and the remaining 11 were discharged.
Our pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19. Calcifediol seems to be able to reduce severity of the disease, but larger trials with groups properly matched will be required to show a definitive answer.
The absence of a specific treatment for SARS-CoV-2 infection led to an intense global effort in order to find new therapeutic interventions and improve patient outcomes. One important feature of ...COVID-19 pathophysiology is the activation of immune cells, with consequent massive production and release of inflammatory mediators that may cause impairment of several organ functions, including the brain. In addition to its classical role as a neurotransmitter, serotonin (5-hydroxytryptamine, 5-HT) has immunomodulatory properties, downregulating the inflammatory response by central and peripheral mechanisms. In this review, we describe the roles of 5-HT in the regulation of systemic inflammation and the potential benefits of the use of specific serotonin reuptake inhibitors as a coadjutant therapy to attenuate neurological complications of COVID-19.
Sepsis is a life-threatening condition induced by a deregulated host response to severe infection. Post-sepsis syndrome includes long-term psychiatric disorders, such as persistent anxiety and ...post-traumatic stress disorder, whose neurobiological mechanisms remain unknown. Using a reference mouse model of sepsis, we showed that mice that recovered from sepsis further developed anxiety-related behaviours associated with an exaggerated fear memory. In the brain, sepsis induced an acute pathological activation of a specific neuronal population of the central nucleus of the amygdala, which projects to the ventral bed nucleus of the stria terminalis. Using viral-genetic circuit tracing and in vivo calcium imaging, we observed that sepsis induced persistent changes in the connectivity matrix and in the responsiveness of these central amygdala neurons projecting to the ventral bed nucleus of the stria terminalis. The transient and targeted silencing of this subpopulation only during the acute phase of sepsis with a viral pharmacogenetic approach, or with the anti-epileptic and neuroprotective drug levetiracetam, prevented the subsequent development of anxiety-related behaviours. Specific inhibition of brain anxiety and fear circuits during the sepsis acute phase constitutes a preventive approach to preclude the post-infection psychiatric outcomes.
Deep Learning for PET Image Reconstruction Reader, Andrew J.; Corda, Guillaume; Mehranian, Abolfazl ...
IEEE transactions on radiation and plasma medical sciences,
2021-Jan., 2021-1-00, 20210101, Letnik:
5, Številka:
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Journal Article
Recenzirano
Odprti dostop
This article reviews the use of a subdiscipline of artificial intelligence (AI), deep learning , for the reconstruction of images in positron emission tomography (PET). Deep learning can be used ...either directly or as a component of conventional reconstruction, in order to reconstruct images from noisy PET data. The review starts with an overview of conventional PET image reconstruction and then covers the principles of general linear and convolution-based mappings from data to images, and proceeds to consider nonlinearities, as used in convolutional neural networks (CNNs). The direct deep-learning methodology is then reviewed in the context of PET reconstruction. Direct methods learn the imaging physics and statistics from scratch, not relying on a priori knowledge of these models of the data. In contrast, model-based or physics-informed deep-learning uses existing advances in PET image reconstruction, replacing conventional components with deep-learning data-driven alternatives, such as for the regularization. These methods use trusted models of the imaging physics and noise distribution, while relying on training data examples to learn deep mappings for regularization and resolution recovery. After reviewing the main examples of these approaches in the literature, the review finishes with a brief look ahead to future directions.
Long-chain polyunsaturated fatty acids (LC-PUFAs) such as arachidonic (ARA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids are essential components of biomembranes, particularly in neural ...tissues. Endogenous synthesis of ARA, EPA and DHA occurs from precursor dietary essential fatty acids such as linoleic and α-linolenic acid through elongation and Δ5 and Δ6 desaturations. With respect to desaturation activities some noteworthy differences have been noted in vertebrate classes. In mammals, the Δ5 activity is allocated to the Fads1 gene, while Fads2 is a Δ6 desaturase. In contrast, teleosts show distinct combinations of desaturase activities (e.g. bifunctional or separate Δ5 and Δ6 desaturases) apparently allocated to Fads2-type genes. To determine the timing of Fads1-Δ5 and Fads2-Δ6 evolution in vertebrates we used a combination of comparative and functional genomics with the analysis of key phylogenetic species. Our data show that Fads1 and Fads2 genes with Δ5 and Δ6 activities respectively, evolved before gnathostome radiation, since the catshark Scyliorhinus canicula has functional orthologues of both gene families. Consequently, the loss of Fads1 in teleosts is a secondary episode, while the existence of Δ5 activities in the same group most likely occurred through independent mutations into Fads2 type genes. Unexpectedly, we also establish that events of Fads1 gene expansion have taken place in birds and reptiles. Finally, a fourth Fads gene (Fads4) was found with an exclusive occurrence in mammalian genomes. Our findings enlighten the history of a crucially important gene family in vertebrate fatty acid metabolism and physiology and provide an explanation of how observed lineage-specific gene duplications, losses and diversifications might be linked to habitat-specific food web structures in different environments and over geological timescales.
Glyphosate (N-(phosphonomethyl) glycine) is a post-emergence, non-selective, foliar herbicide. Around 200millionliters of this herbicide are applied every year in Argentina, where the main ...agricultural practice is no-till (NT), accounting for 78.5% of the cultivated land. In this work, we studied the adsorption of glyphosate in different soils under long-term management (more than 16years) of NT and conventional tillage (CT). Samples were taken from different regions of Argentina corresponding to: Paraná soil (PAR), a silty clay loam soil (<37% clay), Manfredi (MAN) and Pergamino (PER), both silty loam soils (<26% clay). We found that the adsorption was very high in all the soils, and it was particularly influenced by the soil clay content and CEC and negatively related to pH and phosphorus. In general, the adsorption coefficient (Kf) was higher in the CT samples. We also studied the vertical transport of glyphosate in undisturbed columns (15cm long) and compared the effect of NT and CT. Less than 0.24% of the applied pesticide leached in all soils. No significant difference was found between the total amount of leached glyphosate between soils or tillage practice. The highest glyphosate concentration (67.53% of the initially applied doses) was found in the top 5cm of the columns. The strong retention of glyphosate to the soil matrix, as confirmed by the high Kf values obtained in the isotherm studies, was the dominant factor influencing glyphosate mobility through the soil profile.
•Glyphosate was strongly sorbed in all the studied soils.•The Kf was influenced positively by clay content, and negatively by the soil pH and P-Bray.•Small amounts of glyphosate were transported through the undisturbed columns.•Most of the glyphosate and AMPA was found in the top 5cm of the soil columns.•Tillage practice did not have an influence in the leaching of glyphosate.
Resveratrol is a polyphenol found in grapes and red wines. Interest in this polyphenol has increased due to its pharmacological cardio- and neuroprotective, chemopreventive, and antiaging effects, ...among others. Nevertheless, its pharmacokinetic properties are less favorable, since the compound has poor bioavailability, low water solubility, and is chemically unstable. To overcome these problems, we developed two novel resveratrol nanodelivery systems based on lipid nanoparticles to enhance resveratrol's oral bioavailability for further use in medicines, supplements, and nutraceuticals.
Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) loaded with resveratrol were successfully produced by a modified hot homogenization technique. These were completely characterized to evaluate the quality of the developed resveratrol-loaded nanoparticles.
Cryo-scanning electron microscopy morphology studies showed spherical and uniform nanoparticles with a smooth surface. An average resveratrol entrapment efficiency of ~70% was obtained for both SLNs and NLCs. Dynamic light scattering measurements gave a Z-average of 150-250 nm, polydispersity index of ~0.2, and a highly negative zeta potential of around -30 mV with no statistically significant differences in the presence of resveratrol. These characteristics remained unchanged for at least 2 months, suggesting good stability. Differential scanning calorimetry studies confirmed the solid state of the SLNs and NLCs at both room and body temperatures. The NLCs had a less ordered crystalline structure conferred by the inclusion of the liquid lipid, since they had lower values for phase transition temperature, melting enthalpy, and the recrystallization index. The presence of resveratrol induced a disorder in the crystal structure of the nanoparticles, suggesting a favoring of its entrapment. The in vitro release studies on conditions of storage showed a negligible resveratrol release over several hours for both nanosystems and the in vitro simulation of gastrointestinal transit showed that the resveratrol remained mostly associated with the lipid nanoparticles after their incubation in digestive fluids.
Both nanodelivery systems can be considered suitable carriers for oral administration, conferring protection to the incorporated resveratrol and allowing a controlled release after uptake.
Site-specific management demands the identification of subfield regions with homogeneous characteristics (management zones). However, determining subfield areas is difficult because of complex ...correlations and the spatial variability of soil properties and nutrient concentrations, responsible for variations in crop yields within the field. We evaluated whether apparent electrical conductivity (ECₐ) is a potential estimator of soil properties and nutrients, and a tool for the delimitation of homogeneous zones. Two field sites with several soil series were studied in southeastern Cordoba Province, Argentina. Soil properties and nutrient concentrations were compared with ECₐ using principal components (PC)- stepwise regression and ANOVA. The PC-stepwise regression showed that soil properties (pH, EC₁:₂.₅, CEC, SOM) and nutrients (Na⁺², Mg⁺², Mn⁺², Cu⁺², Ca⁺², Zn⁺², Fe⁺²) are key loading factors to explain the ECₐ (R²>0.90). In contrast, K⁺, P, NO₃⁻–N and SO₄⁻²–S), content were not able to explain the ECₐ. The ANOVA showed that ECₐ measurements successfully delimited two homogeneous soil zones associated with the spatial distribution of soil properties and some nutrients (Na⁺², Mg⁺², Mn⁺², Cu⁺², Ca⁺², Zn⁺², Fe⁺²). These results suggest that field-scale ECₐ maps have the potential to design sampling zones to implement site-specific management strategies.
Glyphosate is the most used herbicide in Argentina, accounting for 62% of the commercialized pesticides on the market. It is used as a weed controller in no-till systems, and it is also applied to ...various genetically modified crops (e.g., soybean, corn, and cotton). Although it has a high solubility in water, it tends to adsorb and accumulate in agricultural soils. The main objectives of this work were to compare the dissipation of glyphosate and the accumulation of its metabolite aminomethylphosphonic acid (AMPA) over time in three soils from agricultural areas of Argentina under long-term management with no-till (NT) and conventional tillage (CT) practices. There were no differences in dissipation between NT and CT, indicating that the glyphosate-degrading microflora was not modified by the different tillage managements. Moreover, tillage practices did not alter the general soil properties; therefore, glyphosate bioavailability was not affected by NT or CT practice. Forty percent of the applied glyphosate was degraded within the first three days in all soils, indicating a fast initial dissipation rate. However, the dissipation rate considerably decreased over time, and the degradation kinetics followed a bi-exponential (or two-compartment) kinetic model. No differences were found between tillage practices. Dissipation was not related to the microbial activity measured as soil respiration. The fast decrease in the concentration of glyphosate at the beginning of the dissipation study was not reflected in an increase in the concentration of AMPA. The estimated half-lives for glyphosate ranged between 9 and 38 d. However, glyphosate bioavailability decreases over time, as it is strongly adsorbed to the soil matrix. This increases its residence time, which may lead to its accumulation in agricultural soils.
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