Fenton reaction was used to produce hydroxyl radicals under conditions similar to AOPs with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a spin trap agent in electron paramagnetic resonance (EPR) ...analysis. A theoretical kinetics model was developed to determine conditions under which the spin-adduct DMPO-OH is not further oxidized by Fe3+ and excessive radicals, so that hydroxyl radicals concentration could be accurately inferred. Experiments were designed based upon the model and H2O2 and Fe2+ concentrations were varied from 1 to 100 mM and from 0.1 to 10 mM, respectively, with a constant H2O2: Fe2+ ratio of 10:1. Results confirmed that DMPO concentration should be at least 20 times higher than the concentration of H2O2 and 200 times higher than iron concentration to produce stable DMPO-OH EPR signal. When DMPO: H2O2 ratio varied from 1 to 10, DMPO-OH could generate intermediates and be further oxidized leading to the apparition of an additional triplet. This signal was attributed to a paramagnetic dimer: its structure and a formation mechanism were proposed. Finally, the utilization of sodium sulfite and catalase to terminate Fenton reaction was discussed. Catalase appeared to be compatible with DMPO. However, sodium sulfite should be avoided since it reacted with DMPO-OH to form DMPO-SO3.
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•Concentrations in Fenton reagent similar to AOPs/EAOPs were used.•A theoretical model was developed and experiments were based on this model.•DMPO should be respectively 20 and 200 times higher than H2O2 and Fe2+.•When Fenton reagent is in excess, DMPO-OH is degraded into a paramagnetic dimer.•Utilization of catalase as a H2O2 quencher is compatible with DMPO as a spin trap.
There is compelling evidence that the human cerebellum is engaged in a wide array of motor and cognitive tasks. A fundamental question centers on whether the cerebellum is organized into distinct ...functional subregions. To address this question, we employed a rich task battery designed to tap into a broad range of cognitive processes. During four functional MRI sessions, participants performed a battery of 26 diverse tasks comprising 47 unique conditions. Using the data from this multi-domain task battery, we derived a comprehensive functional parcellation of the cerebellar cortex and evaluated it by predicting functional boundaries in a novel set of tasks. The new parcellation successfully identified distinct functional subregions, providing significant improvements over existing parcellations derived from task-free data. Lobular boundaries, commonly used to summarize functional data, did not coincide with functional subdivisions. The new parcellation provides a functional atlas to guide future neuroimaging studies.
Guideline-based management of asthma focuses on disease severity and choosing the appropriate medical therapy to control symptoms and reduce the risk of exacerbations. However, irrespective of asthma ...severity and often despite optimal medical therapy, patients may experience acute exacerbations of symptoms and a loss of disease control. Asthma exacerbations are most commonly triggered by viral respiratory infections, particularly with human rhinovirus. Given the importance of these events to asthma morbidity and health care costs, we will review common inciting factors for asthma exacerbations and approaches to prevent and treat these events.
Nanocarriers have emerged as a powerful alternative for cancer therapy. Indeed, they are promising candidates to tackle the acquired resistance of surviving cells against antiproliferative drugs - ...the so-called multidrug resistance (MDR) phenomenon - which has arisen as one of the major clinical issues of chemotherapy. Among nanocarriers, this review focuses on the recent approaches based on tailored mesoporous silica nanoparticles (MSNs) that could overcome this problem. Areas covered: Herein we summarize the current efforts developed to provide MSN-based nanosystems of enhanced dual therapeutic action against diseased cells. This can be accomplished by three main approaches: i) increasing nanosystems' killing capability towards particular cells by enhancing both recognition and specificity; ii) increasing the apoptotic effect throughout co-delivery of several drugs; or iii) combining drug delivery with apoptosis induced by physical methods. Expert opinion: The development of multifunctional nanosystems able to exert the optimal therapeutic action through the minimal administration constitutes a major challenge in nanomedicine. Recent developments in advanced MSN-based platforms for drug delivery represent promising avenues in the management of MDR associated with cancer therapy. All strategies discussed in this manuscript demonstrate improvements against difficult-to-treat tumors.
One important approach to human brain mapping is to define a set of distinct regions that can be linked to unique functions. Numerous brain parcellations have been proposed, using cytoarchitectonic, ...structural, or functional magnetic resonance imaging (fMRI) data. The intrinsic smoothness of brain data, however, poses a problem for current methods seeking to compare different parcellations. For example, criteria that simply compare within‐parcel to between‐parcel similarity provide even random parcellations with a high value. Furthermore, the evaluation is biased by the spatial scale of the parcellation. To address this problem, we propose the distance‐controlled boundary coefficient (DCBC), an unbiased criterion to evaluate discrete parcellations. We employ this new criterion to evaluate existing parcellations of the human neocortex in their power to predict functional boundaries for an fMRI data set with many different tasks, as well as for resting‐state data. We find that common anatomical parcellations do not perform better than chance, suggesting that task‐based functional boundaries do not align well with sulcal landmarks. Parcellations based on resting‐state fMRI data perform well; in some cases, as well as a parcellation defined on the evaluation data itself. Finally, multi‐modal parcellations that combine functional and anatomical criteria perform substantially worse than those based on functional data alone, indicating that functionally homogeneous regions often span major anatomical landmarks. Overall, the DCBC advances the field of functional brain mapping by providing an unbiased metric that compares the predictive ability of different brain parcellations to define brain regions that are functionally maximally distinct.
We propose a new unbiased evaluation criterion (distance‐controlled boundary coefficient DCBC) for brain parcellations to overcome the drawback of existing evaluation criteria that are biased by spatial smoothness. Using DCBC, task‐evoked, and resting‐state functional magnetic resonance imaging data, we found resting‐state group parcellations predict task‐based functional boundaries very well, anatomical atlases predict functional boundaries no better than chance, and multi‐modal parcellations do not improve on resting‐state parcellations.
Biodegradable block copolymers have been obtained as promising biomaterials because their hydrophilicity, mechanical and physical properties can be manipulated by combining different chemical ...structures or adjusting the ratio of the constituting blocks. This article reviews recent literature on the crystallization and morphology of biodegradable block copolymers with at least one crystallizable component. Emphasis has been placed on novel double crystalline diblock copolymers. These properties are important to define the final optical and mechanical performance as well as the rate of biodegradation and drug release kinetics. Additionally, block copolymers with biostable components such as polyethylene and poly(ethylene oxide) are also considered. The characterization of these systems by Differential Scanning Calorimetry, Transmission Electron Microscopy, Small-angle and Wide-angle X-ray Scattering and Polarized Light Optical Microscopy are considered in detail. The effects that each block has on the location of the thermal transitions and on the nucleation and crystallization kinetics of the other blocks are also discussed. The crystallization kinetics of each block can be dramatically affected by the presence of the other, and the magnitude of the effect is a function of the segregation strength. Complicated morphology formation and competition effects during the crystallization of two different crystalline blocks are also highlighted. Other many interesting effects have been found for either miscible or immiscible biodegradable block copolymers; amongst them, homogeneous nucleation, sequential or coincident crystallization, fractionated crystallization and fractionated melting can be mentioned. Also different superstructural morphologies such as double concentric spherulites with peculiar changes in their birefringence patterns have been reported for miscible or weakly segregated diblock copolymers as well as distinct nanoscale microdomains for strongly segregated systems.
The rise and development of nanotechnology has enabled the creation of a wide number of systems with new and advantageous features to treat cancer. However, in many cases, the lone application of ...these new nanotherapeutics has proven not to be enough to achieve acceptable therapeutic efficacies. Hence, to avoid these limitations, the scientific community has embarked on the development of single formulations capable of combining functionalities. Among all possible components, silica-either solid or mesoporous-has become of importance as connecting and coating material for these new-generation therapeutic nanodevices. In the present review, the most recent examples of fully inorganic silica-based functional composites are visited, paying particular attention to those with potential biomedical applicability. Additionally, some highlights will be given with respect to their possible biosafety issues based on their chemical composition.
The first postnatal year is characterized by the most dramatic functional network development of the human lifespan. Yet, the relative sequence of the maturation of different networks and the impact ...of socioeconomic status (SES) on their development during this critical period remains poorly characterized. Leveraging a large, normally developing infant sample with multiple longitudinal resting-state functional magnetic resonance imaging scans during the first year (N = 65, scanned every 3 months), we aimed to delineate the relative maturation sequence of 9 key brain functional networks and examine their SES correlations. Our results revealed a maturation sequence from primary sensorimotor/auditory to visual to attention/default-mode, and finally to executive control networks. Network-specific critical growth periods were also identified. Finally, marginally significant positive SES-brain correlations were observed at 6 months of age for both the sensorimotor and default-mode networks, indicating interesting SES effects on functional brain maturation. To the best of our knowledge, this is the first study delineating detailed longitudinal growth trajectories of all major functional networks during the first year of life and their SES correlations. Insights from this study not only improve our understanding of early brain development, but may also inform the critical periods for SES expression during infancy.
Many, and perhaps all, oceanic island basalts (OIB) clearly contain a component of crustal materials that have been returned to the mantle through subduction or other processes. One of the first ...recycled materials to be identified as a potential source of OIB was mid-ocean ridge basalt (MORB), and this was later fine-tuned as having a long time-integrated (b.y.) high U/Pb ratio or high μ (HIMU) and producing OIB with the most radiogenic Pb isotopic ratios (206Pb/204Pb>20). However, it is becoming more evident that the compositional connection between subducted MORB and HIMU basalts is problematic. As an alternative hypothesis, a small amount (a few %) of recycled Archaean marine carbonates (primarily CaCO3) is proposed to be the main source of the distinct 206Pb/204Pb, 207Pb/204Pb and 87Sr/86Sr isotopic and major-trace element compositions of classic HIMU and post-Archaean marine carbonates for younger HIMU or the so-called FOZO mantle source. As an extension of the hypothesis, a conceptual model that combines the separate evolutionary histories of ancient oceanic lithosphere, which is the source of OIB, and upper mantle, which is the source of MORB, is also proposed. The model claims that FOZO mainly consists of the lithospheric mantle portion of the ancient metamorphosed oceanic slabs that have accumulated in the deep mantle. Such an ultramafic source is geochemically depleted due to prior extraction of basaltic melt plus removal of the enriched subduction component from the slab through dehydration and metamorphic processes. Combined with other proposed models in the literature, the conceptual model can provide reasonable solutions for the 208Pb/204Pb, 143Nd/144Nd, 176Hf/177Hf, and 3He/4He isotopic paradoxes or complexities of oceanic lavas. Although these simultaneous solutions for individual paradoxes are qualitative and non-unique, these are unified under a single, marine carbonate recycling hypothesis.
•Recycled marine carbonate is a natural HIMU and has low 87Sr/86Sr and Rb/Sr ratios.•FOZO represents the subducted lithospheric mantle and universal source of OIB.•Subducted slab has high U/Pb (Pb paradox) and low Th/U (kappa conundrum).•Garnet and high Hf (low Lu/Hf) in subducted slab are responsible for Hf paradox.•Ancient helium in subducted slab is the source of high 3He/4He OIB.
Intertrigo is a skin fold dermatitis often requiring recurrent treatment with topical antiseptics or antibiotics, which can select antimicrobial resistance. To minimize this risk, we tested the ...effectiveness of medical-grade Manuka honey at treating intertrigo as compared to a placebo hydrogel. We additionally characterized the culturable microbial flora of intertrigo and recorded any adverse effect with either treatment. During this randomized, placebo-controlled, double-blinded, adaptive group-sequential trial, the owners washed the affected sites on their dog with water, dried and applied a thin film of either the honey or the placebo product once daily for 21 days. Cytological and lesional composite scores, owner-assessed pruritus, and microbial cultures were assessed prior to treatment and on Day-22. The fixed effects of time, treatment, and animal-related variables on the pruritus and on each composite score, accounting for random dog effect, were estimated separately with generalized linear mixed models for repeated count outcomes (α = 0.05). The null hypothesis of equal treatment effects was rejected at the first interim analysis. The placebo (n = 16 dogs) outperformed the medical honey (n = 13 dogs) at improving both the cytological score (Treatment×Time = -0.35±0.17; P = 0.04) and clinical score (Treatment×Time = -0.28±0.13; P = 0.04). A microbial burden score higher than 4 increased the severity of the cytological score (dichotomous score: 0.29±0.11; P = 0.01), which in turn increased the severity of the clinical score and pruritus score. For every unit increase in cytological score, the linear predictor of clinical score increased by 0.042±0.019 (P = 0.03), and the one of pruritus score increased by 0.12±0.05 (P = 0.01). However, medical honey outperformed the placebo at alleviating the dog's owner-assessed pruritus after statistically controlling for masking effects (Time = -0.94±0.24; P = 0.002; and Treatment×Time = 0.80±0.36; P = 0.04). Unilateral tests of the least-square mean estimates revealed that honey only significantly improved the pruritus (Hommel-adjusted P = 0.003), while the placebo only improved the cytological and clinical scores (Hommel-adjusted P = 0.01 and 0.002, respectively). Taken together, these results question the value of Manuka honey at treating nasal intertrigo in dogs.
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