Residual viraemia is a major obstacle to HIV-1 eradication in subjects receiving HAART. The intensification with raltegravir could impact latent reservoirs and might lead to a reduction of plasma ...HIV-1 viraemia (viral load VL), complementary DNA intermediates and immune activation.
This was a prospective, open-label, randomized study comprising 69 individuals on suppressive HAART randomly assigned 2:1 to add raltegravir during 48 weeks.
Total and integrated HIV-1 DNA, and ultrasensitive VL remained stable despite intensification. There was a significant increase in episomal HIV DNA at weeks 2-4 in the raltegravir group returning to baseline levels at week 48. Median CD4(+) T-cell counts increased 124 and 80 cells/µl in the intensified and control groups after 48 weeks (P=0.005 and P=0.027, respectively), without significant differences between groups. No major changes were observed in activation of CD4(+) T-cells. Conversely, raltegravir intensification significantly reduced activation of CD8(+) T-cells at week 48 (HLA-DR(+)CD38(+), P=0.005), especially in the memory compartment (CD38(+) of CD8(+)CD45RO(+), P<0.0001). Linear mix models also depicted a larger decrease in CD8(+) T-cell activation in the intensification group (P=0.036 and P=0.010, respectively). Raltegravir intensification was not associated to any particular adverse event.
Intensification of HAART with raltegravir during 48 weeks was safe and associated with a significant decrease in CD8(+) T-cell activation, and a transient increase of episomal HIV-1 DNA. However, raltegravir did not significantly contribute to changes in CD4(+) T-cell counts, ultrasensitive VL, and total and integrated HIV-1 DNA. These findings suggest that raltegravir impacts residual HIV-1 replication and support new strategies to impair HIV-1 persistence. ClinicalTrials.gov identifier: NCT00554398.
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This research addresses the development and in vitro evaluation of a microparticulate system intended for intestine-targeted delivery of curcumin (CRM), a natural polyphenol with ...anti-inflammatory properties. Microspheres (Ms) based on zein (ZN) and Gantrez® AN119 (PVMMA) were prepared by spray-drying and coated with a pH-sensitive polymer (Eudragit® FS30D). An experimental design was performed to optimize the microparticulate formulation. A detailed characterization of systems was carried out by SEM, DSC, FTIR, particle size, ζ potential measurements and in vitro CRM release. The optimized formulation was evaluated in LPS-stimulated RAW 264.7 macrophages to investigate its anti-inflammatory activity. FTIR and DSC studies suggest a predominant presence of α-helix structure for ZN when formulated and also, a strong interaction between components. The stabilization of α-helix by PVMMA or CRM would take place by hydrogen bonds. Although the encapsulation efficiency was high (89%) for ZN/PVMMA Ms, the coating process with Eudragit® led to an EE decrease of 62%. Coating of Ms was found to retain a 20% of drug within 6h of release, although a strong initial burst release was observed. Cells viability and apoptosis were not affected when cells were co-incubated with coated Ms with CRM. The exposure of unstimulated cells to Ms did not show any effect on NO and PGE2 production. However, a reduction in NO and PGE2 production was obtained when CRM-loaded Ms were co-incubated with stimulated macrophages. Further, this inhibition was significantly higher compared to the decrease obtained when Ms with pure CRM were used in culture, which suggested a synergistic effect of CRM and Ms. Finally, CRM-loaded Ms caused a significant inhibition of analysed pro-inflammatory cytokines (TNFα, IL-1β, NOS2, COX-2) in macrophages stimulated with LPS.
All these results confirm the advantageous features of ZN/PVMMA microspheres as a serious alternative for delivering CRM to reduce the inflammatory activity at intestinal regions affected by inflammatory bowel diseases.
We present an overview of the factors as well as post processing tools allowing optimization of magnetic softness and GMI effect of rapidly quenched materials: microwires and ribbons. Generally, low ...coercivity and high GMI effect have been observed in as-prepared Co-rich compositions. Annealing at adequate conditions can be very effective for manipulation of the magnetic properties and GMI effect of amorphous and nanocrystalline rapidly quenched materials. After annealing of Co-rich compositions, we can observe transformation of inclined hysteresis loops to rectangular. However, at certain annealing conditions GMI effect can be improved. Using stress-annealing, GMI effect of both Fe-rich and Co-rich microwires as well as of amorphous ribbons can be improved. On the other hand, in Fe-rich FeCuNbSiB microwires after appropriate annealing we observed considerable magnetic softening and GMI effect enhancement. The other promising post-processing allowing GMI effect optimization is Joule heating.
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•Trends in optimization of GMI effect in amorphous and nanocrystalline materials.•Magnetic softening of Fe-rich microwires after stress-annealing or nanocrystallization.•Improvement of GMI effect after Joule heating of Co-rich microwires.•Optimization of GMI effect after post-processing of Co-rich amorphous ribbons.•Improvement of GMI effect after annealing and stress-annealing of Co-rich microwires.
Objectives
The aim of the study was to assess the rates of discontinuation of integrase inhibitor regimens because of any neuropsychiatric adverse event (NPAE) and the factors associated with ...discontinuation.
Methods
A population‐based, prospective, multicentre cohort study was carried out. Treatment‐naïve subjects starting therapy with a regimen containing integrase inhibitors, or those switching to such a regimen, with plasma HIV‐1 RNA < 50 HIV‐1 RNA copies/mL in 14 hospitals in Catalonia or the Balearic Islands (Spain) were included in the study. Every discontinuation because of adverse events (AEs) was double‐checked directly with treating physicians. Multivariable Cox models identified factors correlated with discontinuation.
Results
A total of 4165 subjects (37% treatment‐naïve) started regimens containing dolutegravir (n = 1650; 91% with abacavir), raltegravir (n = 930) or elvitegravir/cobicistat (n = 1585). There were no significant differences among regimens in the rate of discontinuation because of any AE. Rates of discontinuation because of NPAEs were low but higher for dolutegravir/abacavir/lamivudine 2.1%; 2.9 (95% confidence interval (CI) 2.0, 4.2) discontinuations/100 patients/year versus elvitegravir/cobicistat (0.5%; 0.8 (95% CI 0.3, 1.5) discontinuations/100 patients/year, with significant differences among centres for dolutegravir/abacavir/lamivudine and NPAEs (P = 0.003). We identified an association of female gender and lower CD4 count with increased risk of discontinuation because of any AE Incidence ratio (IR) 2.3 (95% CI 1.4, 4.0) and 1.8 (95% CI 1.1, 2.8), respectively. Female gender, age > 60 years and abacavir use were not associated with NPAE discontinuations. NPAEs were commonly grade 1–2, and had been present before and improved after drug withdrawal.
Conclusions
In this large prospective cohort study, patients receiving dolutegravir, raltegravir or elvitegravir/cobicistat did not show significant differences in the rate of discontinuation because of any toxicity. The rate of discontinuations because of NPAEs was low, but was significantly higher for dolutegravir than for elvitegravir/cobicistat, with significant differences among centres, suggesting that greater predisposition to believe that a given adverse event is caused by a given drug of some treating physicians might play a role in the discordance seen between cohorts.
There are multiple measures for assessment of physical function in knee osteoarthritis (OA), but each has its strengths and limitations. The GaitSmart® system, which uses inertial measurement units ...(IMUs), might be a user-friendly and objective method to assess function. This study evaluates the validity and responsiveness of GaitSmart® motion analysis as a function measurement in knee OA and compares this to Knee Injury and Osteoarthritis Outcome Score (KOOS), Short Form 36 Health Survey (SF-36), 30s chair stand test, and 40m self-paced walk test.
The 2-year Innovative Medicines Initiative-Applied Public-Private Research enabling OsteoArthritis Clinical Headway (IMI-APPROACH) knee OA cohort was conducted between January 2018 and April 2021. For this study, available baseline and 6 months follow-up data (n = 262) was used. Principal component analysis was used to investigate whether above mentioned function instruments could represent one or more function domains. Subsequently, linear regression was used to explore the association between GaitSmart® parameters and those function domains. In addition, standardized response means, effect sizes and t-tests were calculated to evaluate the ability of GaitSmart® to differentiate between good and poor general health (based on SF-36). Lastly, the responsiveness of GaitSmart® to detect changes in function was determined.
KOOS, SF-36, 30s chair test and 40m self-paced walk test were first combined into one function domain (total function). Thereafter, two function domains were substracted related to either performance based (objective function) or self-reported (subjective function) function. Linear regression resulted in the highest R2 for the total function domain: 0.314 (R2 for objective and subjective function were 0.252 and 0.142, respectively.). Furthermore, GaitSmart® was able to distinguish a difference in general health status, and is responsive to changes in the different aspects of objective function (Standardized response mean (SRMs) up to 0.74).
GaitSmart® analysis can reflect performance based and self-reported function and may be of value in the evaluation of function in knee OA. Future studies are warranted to validate whether GaitSmart® can be used as clinical outcome measure in OA research and clinical practice.
Context. The Polarimetric and Helioseismic Imager (SO/PHI), on board the Solar Orbiter mission, is the first photospheric magnetograph and tachograph to observe the Sun from outside the Sun-Earth ...line. The Full Disc Telescope (FDT) of SO/PHI, images the whole solar disk with a spatial resolution that varies with the distance between the Sun and the spacecraft. Aims. We check for consistency between the magnetic field strength ( B ), the field inclination ( γ ), the line-of-sight (LoS) magnetic component ( B LoS ) and the field azimuth ( ϕ ), inferred by SO/PHI-FDT and the Helioseismic and Magnetic Imager (HMI), on board Solar Dynamics Observatory (SDO), and obtain linear correlation coefficients among them. Methods. We use data from both instruments obtained on 8 March 2022, when the angle between SDO and Solar Orbiter was 3.4° and the solar disk showed four developed active regions. Before comparing the magnetic field products of both instruments we perform a precise alignment of the data, including a matching of the plate scale. Further, in order to improve the homogeneity of the compared data products, the SDO/HMI data were convolved with the SO/PHI-FDT point spread function (PSF). The linear correlation coefficients are obtained through a linear regression of SDO/HMI to SO/PHI-FDT. Results. The two instruments yield comparable magnetic field data products. The slope coefficients for a linear fit are 1.37 for B , 1.11 for γ , 1.35 for B LoS and 1 for the azimuth. The corresponding fit offsets are −94 G, −9.8°, 5.2 G and 0.1°, respectively. The agreement between both instruments is significantly better when we take into account the different spatial resolution of both instruments. The fitting results vary slightly depending on the analyzed active region except for one of the four active regions, which shows larger differences and has been excluded from the comparison. The comparison of the LoS magnetic field products from SDO/HMI at 45 s and 720 s with SO/PHI-FDT shows a slope value of 1.17, with the offset less than 6 G, in both cases.
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•Soil washing performance after nZVI addition was examined.•Dilution effect caused by nZVI was considered for metallurgical accounting purposes.•Nanoparticle addition improved PTE ...removal.•nZVIs were selective for Cu, Pb and Sb.
The present study focuses on soil washing enhancement via soil pretreatment with nanoscale zero-valent iron (nZVI) for the remediation of potentially toxic elements. To this end, soil polluted with As, Cu, Hg, Pb and Sb was partitioned into various grain sizes (500–2000, 125–500 and <125 μm). The fractions were pretreated with nZVI and subsequently subjected, according to grain size, to Wet-High Intensity Magnetic Separation (WHIMS) or hydrocycloning. The results were compared with those obtained in the absence of nanoparticles.
An exhaustive characterization of the magnetic signal of the nanoparticles was done. This provided valuable information regarding potentially toxic elements (PTEs) fate, and allowed a metallurgical accounting correction considering the dilution effects caused by nanoparticle addition.
As a result, remarkable recovery yields were obtained for Cu, Pb and Sb, which concentrated with the nZVI in the magnetically separated fraction (WHIMS tests) and underflow (hydrocyclone tests). In contrast, Hg, concentrated in the non-magnetic fraction and overflow respectively, while the behavior of As was unaltered by the nZVI pretreatment. All things considered, the addition of nZVI enhanced the efficiency of soil washing, particularly for larger fractions (125–2000 μm). The proposed methodology lays the foundations for nanoparticle utilization in soil washing operations.
Yeast selection for the wine industry in Spain started in 1950 for the understanding of the microbial ecology, and for the selection of optimal strains to improve the performance of alcoholic ...fermentation and the overall wine quality. This process has been strongly developed over the last 30 years, firstly on Saccharomyces cerevisiae, and, lately, with intense activity on non-Saccharomyces. Several thousand yeast strains have been isolated, identified and tested to select those with better performance and/or specific technological properties. The present review proposes a global survey of this massive ex-situ preservation of eukaryotic microorganisms, a reservoir of biotechnological solutions for the wine sector, overviewing relevant screenings that led to the selection of strains from 12 genera and 22 species of oenological significance. In the first part, the attention goes to the selection programmes related to relevant wine-producing areas (i.e. Douro, Extremadura, Galicia, La Mancha and Uclés, Ribera del Duero, Rioja, Sherry area, and Valencia). In the second part, the focus shifted on specific non-Saccharomyces genera/species selected from different Spanish and Portuguese regions, exploited to enhance particular attributes of the wines. A fil rouge of the dissertation is the design of tailored biotechnological solutions for wines typical of given geographic areas.
We studied the effect of applied tensile stresses on magnetic properties of Fe- and Co-rich amorphous glass-coated microwires. Rising of magnetic anisotropy field upon tensile stress in Co-rich ...glass-coated microwires is described by a linear dependence. Furthermore, decrease of magnetic susceptibility upon tensile stress is observed in Co-rich microwires. A monotonous increase in the coercivity and the switching field upon tensile applied stress is observed for as-prepared Fe-rich microwire. Stress induced magnetic bistability consisting of transformation of hysteresis and onset of rectangular hysteresis loop upon tensile stress, σ, of about 22.5 MPa is observed in stress-annealed Fe-rich microwires. Such stress-induced magnetic bistability results in considerable growing of coercivity and remanent magnetization in stress-annealed Fe-rich microwires. The rising in the coercivity and the switching field upon applied tensile stresses in stress-annealed Fe-rich microwires with stress induced magnetic bistability (at σ > 22.5 MPa) is roughly described by the σ½ dependence, as previously reported for the wires with spontaneous magnetic bistability. Consequently, stress-annealing of Fe-rich microwire allows beneficial enhancement of the stress dependence of coercivity. Observed dependencies are discussed considering stress dependence of the magnetostriction coefficient in Co-rich glass-coated microwires, internal stresses redistribution and domain structure rearrangement in stress-annealed Fe-rich microwires upon applied tensile stresses.
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•Linear increase in the magnetic anisotropy field upon stress in Co-rich microwires.•Decrease in the magnetic susceptibility upon applied stress in Co-rich microwires.•Observation of stress induced magnetic bistability in stress-annealed Fe-rich microwires.•Enhanced stress dependence of coercivity in stress-annealed Fe-rich microwires.•Observation of σ½ dependence of switching field in stress-annealed Fe-rich microwires.
The purpose of the present investigation is to explore the feasibility of applying the micromix combustion principle (MCP) to design low NOx burners using 100% H2 as fuel for domestic and industrial ...boilers. Previous investigations studying the MCP on stationary and aero gas turbine applications, showed low NOx emissions without flashback risk, which represent the two main issues when burning 100% H2. Since boiler burner operating conditions differ from gas turbine combustors, the present paper studies the MCP through CFD calculations under re-defined conditions for domestic and industrial burners, adapting the energy densities, air-fuel equivalence ratios and pre-heated air temperatures. A reference geometry was built to validate the selected numerical models with experimental results from literature. Afterwards, burners were re-dimensioned following an existing geometry-scaling methodology. The obtained results evidenced that MCP characteristics were still maintained for the defined cases, keeping low NOx values between 4 and 14 ppm. The numerical results were also validated through experimental NOx measurements in a laboratory scale micromix burner prototype. In order to assess the benefits of using hydrogen micromix burners in domestic and industrial boilers, the present work includes a final discussion with practical design considerations. The present study lays the groundwork for complementary experimental research work, which is being carried out in laboratory-scale prototypes.
•MCP is a potential technology for domestic and industrial hydrogen burners.•Low NOx and MCP characteristics are preserved for the defined cases.•The lower entropy production in H2 combustion allows working with higher AFR.•Higher AFR could be beneficial for domestic and industrial low NOx H2 burners.
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