Cisplatin (cis-diamminedichloroplatinum II, CDDP) is a chemotherapeutic agent that induces nephrotoxicity associated with oxidative/nitrosative stress. Sulforaphane (SFN) is an isothiocyanate ...produced by the enzymatic action of myrosinase on glucorophanin, a glucosinolate contained in cruciferous vegetables. SFN is able to induce cytoprotective enzymes through the transcription factor Nrf2. The purpose of this study was to evaluate whether SFN induces a cytoprotective effect on the CDDP-induced nephrotoxicity. Preincubation of LLC-PK1 cells with 0.5–5
μM SFN by 24
h was able to prevent, in a concentration-dependent way, CDDP-induced cell death. Immunofluorescent staining confirmed the nuclear translocation of Nrf2 after treatment with SFN. In the
in vivo studies, CDDP was given to Wistar rats as a sole i.p. injection at a dose of 7.5
mg/kg. SFN (500
μg/kg i.v.) was given two times (24
h before and 24 after CDDP-injection). Animals were killed three days after CDDP-injection. SFN attenuated CDDP-induced renal dysfunction, structural damage, oxidative/nitrosative stress, glutathione depletion, enhanced urinary hydrogen peroxide excretion and the decrease in antioxidant enzymes (catalase, glutathione peroxidase and glutathione-S-transferase). The renoprotective effect of SFN on CDDP-induced nephrotoxicity was associated with the attenuation in oxidative/nitrosative stress and the preservation of antioxidant enzymes.
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•Bismuth terminated BiOX(001) (X = Cl, Br, I) surfaces are stable.•Engineering the BiOX surfaces with Bi-vacancies increases the reactivity.•Electrostatic Potential confirms the ...reactivity of the Bi-vacancy induced 2x1 reconstruction.•A Bi-vacancy 2 × 1 reconstruction has been demonstrated through TH-STM calculations.
The bismuth oxyhalides (BiOX, X = Cl, Br, I) are constantly investigated due to their efficient catalytic properties. Here we extend the exploration of the (001) BiOX surfaces, considering different possible surface terminations and defects through a comprehensive ab-initio approach. First-principles thermodynamics are used to analyze the models’ stability. Results show that the Bi-terminated BiOX (1 × 1) surfaces are the most stable at Bi-rich and O-rich chemical potential conditions; At Bi-rich and O-poor conditions, the halogen-terminated BiOX (1 × 1) surfaces become stable. Furthermore, as the Bismuth chemical potential decreases, Bismuth and Oxygen vacancies stabilize the BiOX (2 × 1) surface reconstructions. The BiOX (2 × 1) reconstructions present arrays of ordered Bi and O vacancies along the 010 direction. The models’ electronic properties are computed by the projected density of states, Thersoff-Hamann scanning tunneling microscopy (THSTM) images, and electrostatic potential isosurfaces. The proposed BiOX (2 × 1) surfaces could facilitate nucleophilic attacks at the O surface atoms; consequently, it could be key to promote surface catalytic reactions, such as water splitting.
Context.
The Polarimetric and Helioseismic Imager on board the Solar Orbiter mission (SO/PHI) offers refocusing capabilities to cope with the strongly varying thermal environment of the optical ...system along the spacecraft’s elliptical orbit. The series of images recorded during in-flight focus calibrations can be employed for phase diversity analyses.
Aims.
In this work we infer the wavefront degradation caused by the thermo-optical effects in the High Resolution Telescope (HRT) from images taken during the fine and coarse focus scans performed in the commissioning phase of the instrument. The difference between these two series of images are mainly related to the employed defocused step (smaller for the fine scans) and the signal-to-noise ratio (higher for the coarse scans). We use the retrieved wavefronts to reconstruct the original scene observed during the calibration of the instrument.
Methods.
We applied a generalized phase diversity algorithm that allowed us to use several images taken with different amounts of defocus to sense the wavefront degradation caused by the instrument. The algorithm also uses information from both the inferred wavefront and the series of images to restore the solar scene.
Results.
We find that most of the retrieved Zernike coefficients tend to converge to the same value when increasing the number of images employed for PD for both the fine and the coarse focusing scans. The restored scenes also show signs of convergence, and the merit function is minimized more as
K
increases. Apart from a defocus, the inferred wavefronts are consistent for the two datasets (
λ
/10 −
λ
/11). For the fine scan images, the quiet-sun contrast improves from 4.5% for the original focused image up to about 10%. For the coarse scan images, the contrast of the restored scene is as high as 11%.
Background Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived ...from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions. Objective We sought to investigate the ability of whole-exome screening methods to detect disease-causing variants in patients with PIDDs. Methods Patients with PIDDs from 278 families from 22 countries were investigated by using whole-exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome-tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping. Results A likely molecular diagnosis was achieved in 110 (40%) unrelated probands. Clinical diagnosis was revised in about half (60/110) and management was directly altered in nearly a quarter (26/110) of families based on molecular findings. Twelve PIDD-causing CNVs were detected, including 7 smaller than 30 Kb that would not have been detected with conventional diagnostic CNV arrays. Conclusion This high-throughput genomic approach enabled detection of disease-related variants in unexpected genes; permitted detection of low-grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes.
In this paper we consider a linear KdV equation posed on a bounded interval. We study the behavior of the cost of null controllability when two boundary controls are employed. By means of suitable ...Carleman inequalities and a new exponential dissipation estimate, we prove that uniform null controllability with respect to the dispersion coefficient holds, contrary to the case when one control is used at the left end-point of the interval.
Background: Oral nutritional supplementation (ONS) with or without exercise (EX) could improve muscle mass (MM) in chronic kidney disease. Methods: Patients were randomized into two groups: (1) ONS ...and (2) ONS + EX. Thigh muscle area (cm2) and intramuscular lipid content via attenuation were evaluated at baseline and 6 months with computed tomography (CT) to measure MM quantity and quality. Physical function was measured by six-minute walk test (6 MWT), gait speed, handgrip strength (HGS), and Time Up and Go test (TUG) at baseline and 3 and 6 months. Results: The ONS group (n= 14) showed statistically significant improvement in gait speed and HGS; ONS + EX group (n = 10) showed differences in gait speed, in 6 MWT, and HGS. In the ANOVA (3 times × 2 groups), no differences were observed between groups. Greater effect sizes in favor to ONS + EX group were observed in the 6 MWT (d = 1.02) and TUG test (d = 0.63). Muscle quality at six months revealed a significant trend in favor of the EX-group (p = 0.054). Conclusions: Both groups had improved physical function, and greater effect sizes were seen in the ONS + EX group for the 6 MWT and TUG test. Neither MM quantity or quality was improved in either group.
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Stryphnodendron pulcherrimum (Willd.) Hochr. (Fabaceae) is a native Amazonian tree, popularly known as “barbatimão”. The stem barks of this tree are widely used in folk medicine to ...treat infections, cutaneous and ulcerative wounds, under the form of a suspension of the bark-derived powder. The present study aimed to investigate the in vitro antibacterial and cytotoxic activities of the ethanolic extract of S. pulcherrimum (SPEE). Likewise, to putatively identify the active compounds of the extract by ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Therefore, we aimed to rationalize this observation by turning the bark powder-derived suspension into an ointment (SPEEO) incorporating SPEE (20% w/v). Both the antibacterial action and the acute dermal toxicity were evaluated in rats as animal model. Mortality, body weight changes, feed and water intake, organ weights, histological and biochemical parameters were measured for 14 days post-treatment with no major sign of toxicity. The SPEE showed excellent in vitro antibacterial activity (Minimum Inhibitory Concentration = 100 µg/mL) against Staphylococcus aureus and no in vivo acute dermal toxicity. The SPEEO inhibited up to 85% bacterial growth in a petri dish, with better results than the control standard ointment (Kollagenase®). We putatively identified 13 compounds present in the SPEE, belonging to the class of tannins, including one trimer and two dimers of catechin. Thereby, the data showed SPEEO as a potent antibacterial candidate for herbal medicine preparation.
We report the first discovery of a thick-disk planet, LHS 1815b (TOI-704b, TIC 260004324), detected in the Transiting Exoplanet Survey Satellite (TESS) survey. LHS 1815b transits a bright (V = 12.19 ...mag, K = 7.99 mag) and quiet M dwarf located 29.87 0.02 pc away with a mass of 0.502 0.015 M and a radius of 0.501 0.030 R . We validate the planet by combining space- and ground-based photometry, spectroscopy, and imaging. The planet has a radius of 1.088 0.064 R⊕ with a 3 mass upper limit of 8.7 M⊕. We analyze the galactic kinematics and orbit of the host star LHS 1815 and find that it has a large probability (Pthick/Pthin = 6482) to be in the thick disk with a much higher expected maximal height (Zmax = 1.8 kpc) above the Galactic plane compared with other TESS planet host stars. Future studies of the interior structure and atmospheric properties of planets in such systems using, for example, the upcoming James Webb Space Telescope, can investigate the differences in formation efficiency and evolution for planetary systems between different Galactic components (thick disks, thin disks, and halo).
Objective
There is a paucity of data regarding health care costs associated with damage accrual in systemic lupus erythematosus. The present study was undertaken to describe costs associated with ...damage states across the disease course using multistate modeling.
Methods
Patients from 33 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. Annual data on demographics, disease activity, damage (SLICC/American College of Rheumatology Damage Index SDI), hospitalizations, medications, dialysis, and selected procedures were collected. Ten‐year cumulative costs (Canadian dollars) were estimated by multiplying annual costs associated with each SDI state by the expected state duration using a multistate model.
Results
A total of 1,687 patients participated; 88.7% were female, 49.0% were white, mean ± SD age at diagnosis was 34.6 ± 13.3 years, and mean time to follow‐up was 8.9 years (range 0.6–18.5 years). Mean annual costs were higher for those with higher SDI scores as follows: $22,006 (Canadian) (95% confidence interval 95% CI $16,662, $27,350) for SDI scores ≥5 versus $1,833 (95% CI $1,134, $2,532) for SDI scores of 0. Similarly, 10‐year cumulative costs were higher for those with higher SDI scores at the beginning of the 10‐year interval as follows: $189,073 (Canadian) (95% CI $142,318, $235,827) for SDI scores ≥5 versus $21,713 (95% CI $13,639, $29,788) for SDI scores of 0.
Conclusion
Patients with the highest SDI scores incur 10‐year cumulative costs that are ~9‐fold higher than those with the lowest SDI scores. By estimating the damage trajectory and incorporating annual costs, data on damage can be used to estimate future costs, which is critical knowledge for evaluating the cost‐effectiveness of novel therapies.
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