The Utility of Nasal Challenges to Phenotype Asthma Patients

Asthma is a heterogeneous disease in terms of both phenotype and response to therapy. Therefore, there is a great need for clinically applicable tools allowing for improved patient classification, and selection for specific management approaches. Some interventions are highly helpful in selected patients (e.g., allergen immunotherapy or aspirin desensitization), but they are costly and/or difficult to implement. Currently available biomarkers measurable in peripheral blood or exhaled air display many limitations for asthma phenotyping and cannot identify properly the specific triggers of the disease (e.g., aeroallergens or NSAID). The united airway concept illustrates the relevant epidemiological and pathophysiological links between the upper and lower airways. This concept has been largely applied to patient management and treatment, but its diagnostic implications have been less often explored. Of note, a recent document by the European Academy of Allergy and Clinical Immunology proposes the use of nasal allergen challenge to confirm the diagnosis of allergic asthma. Similarly, the nasal challenge with lysine acetylsalicylate (L-ASA) can be used to identify aspirin-sensitive asthma patients. In this review, we will summarize the main features of allergic asthma and aspirin-exacerbated respiratory disease and will discuss the methodology of nasal allergen and L-ASA challenges with a focus on their capacity to phenotype the inflammatory disease affecting both the upper and lower airways.     

Disclosing the Role of Defect-Engineered Metal–Organic Frameworks in Mixed Matrix Membranes for Efficient CO2 Separation: A Joint Experimental-Computational Exploration

Incorporation of defects in metal–organic frameworks (MOFs) offers new opportunities for manipulating their microporosity and functionalities. The so-called “defect engineering” has great potential to tailor the mass transport properties in MOF/polymer mixed matrix membranes (MMMs) for challenging separation applications, for example, CO₂ capture. This study first investigates the impact of MOF defects on the membrane properties of the resultant MOF/polymer MMMs for CO₂ separation. Highly porous defect-engineered UiO-66 nanoparticles are successfully synthesized and incorporated into a CO₂-philic crosslinked poly(ethylene glycol) diacrylate (PEGDA) matrix. A thorough joint experimental/simulation characterization reveals that defect-engineered UiO-66/PEGDA MMMs exhibit nearly identical filler–matrix interfacial properties regardless of the defect concentrations of their parental UiO-66 filler. In addition, non-equilibrium molecular dynamics simulations in tandem with gas transport studies disclose that the defects in MOFs provide the MMMs with ultrafast transport pathways mainly governed by diffusivity selectivity. Ultimately, MMMs containing the most defective UiO-66 show the most enhanced CO₂/N₂ separation performance—CO₂ permeability = 470 Barrer (four times higher than pure PEGDA) and maintains CO₂/N₂ selectivity = 41—which overcomes the trade-off limitation in pure polymers. The results emphasize that defect engineering in MOFs would mark a new milestone for the future development of optimized MMMs.     

Staphylococcus aureus Exfoliative Toxin E,Oligomeric State and Flip of P186: Implications for Its Action Mechanism

Staphylococcal exfoliative toxins (ETs) are glutamyl endopeptidases that specifically cleave the Glu381-Gly382 bond in the ectodomains of desmoglein 1 (Dsg1) via complex action mechanisms. To date, four ETs have been identified in different Staphylococcus aureus strains and ETE is the most recently characterized. The unusual properties of ETs have been attributed to a unique structural feature, i.e., the 180° flip of the carbonyl oxygen (O) of the nonconserved residue 192/186 (ETA/ETE numbering), not conducive to the oxyanion hole formation. We report the crystal structure of ETE determined at 1.61 Å resolution, in which P186(O) adopts two conformations displaying a 180° rotation. This finding, together with free energy calculations, supports the existence of a dynamic transition between the conformations under the tested conditions. Moreover, enzymatic assays showed no significant differences in the esterolytic efficiency of ETE and ETE/P186G, a mutant predicted to possess a functional oxyanion hole, thus downplaying the influence of the flip on the activity. Finally, we observed the formation of ETE homodimers in solution and the predicted homodimeric structure revealed the participation of a characteristic nonconserved loop in the interface and the partial occlusion of the protein active site, suggesting that monomerization is required for enzymatic activity.     

Increases in nitrogen use efficiency decrease nitrous oxide emissions but can penalize yield in sugarcane

Nutrient Cycling in Agroecosystems - Nitrogen (N) fertilization strategies focused on increasing nitrogen use efficiency (NUE) and decreasing nitrous oxide (N2O) emissions are important for...     

Elevated temperature nanoindentation behaviour of polyamide 6

It has been found, in this study, that there is no close correlation between the tensile and nanoindentation moduli of polyamide 6 (PA6) at high temperatures. It is demonstrated that heat modifies the surface of PA6 specimens, but its effect on the nanomechanical properties is minor. The main spurious factor which affects the nanoindentation results is adhesion, especially at low indentation depths. The overestimation in the measured indentation moduli can be corrected by performing indentations with loads high enough so that the modulus is independent of the applied load. It is concluded that the lack of strict correlations between the tensile and indentation moduli (after corrections of adhesion) is caused by the shift in the glass transition temperature of PA6 owing to the hydrostatic stress imposed by the indenter. Further proof is given with two examples on hydrostatic pressure‐dependent polymers: polytetrafluoroethylene and polycarbonate. Copyright © 2011 Society of Chemical Industry     

New Insights in the Involvement of the Endocannabinoid System and Natural Cannabinoids in Nicotine Dependence

Nicotine, the main psychoactive component in tobacco smoke, plays a major role in tobacco addiction, producing a high morbidity and mortality in the world. A great amount of research has been developed to elucidate the neural pathways and neurotransmitter systems involved in such a complex addictive behavior. The endocannabinoid system, which has been reported to participate in the addictive properties of most of the prototypical drugs of abuse, is also implicated in nicotine dependence. This review summarizes and updates the main behavioral and biochemical data involving the endocannabinoid system in the rewarding properties of nicotine as well as in nicotine withdrawal and relapse to nicotine-seeking behavior. Promising results from preclinical studies suggest that manipulation of the endocannabinoid system could be a potential therapeutic strategy for treating nicotine addiction.     

Influence of different reactor types on Nannochloropsis oculata microalgae culture for lipids and fatty acid production

Greenhouse gases emitted into the atmosphere by burning of fossil fuels cause global warming. One option is obtaining biodiesel. Nannochloropsis oculata was cultured under different light intensities and reactors at 25°C for 21 days with f/2 medium to assess their effects on cell density, lipid, and fatty acids (FAs). N. oculata improved cell density on fed-batch glass tubular reactor (7 L) at 200 μmol E m⁻² s⁻¹, yielding 3.5 × 10⁸ cells ml⁻¹, followed by fed-batch Erlenmeyer flask (1 L) at 650 μmol E m⁻² s⁻¹ with 1.7 × 10⁸ cells ml⁻¹. The highest total lipid contents (% g lipid × g dry biomass⁻¹) were 44.4 ± 0.8% for the reactor (1 L) at 650 μmol E m⁻² s⁻¹ and 35.2 ± 0.2% for the tubular reactor (7 L) at 200 μmol E m⁻² s⁻¹, until twice as high compared with the control culture (Erlenmeyer flask 1 L, 80 μmol E m⁻² s⁻¹) with 21.2 ± 1%. Comparing the total lipid content at 200 μmol E m⁻² s⁻¹, tubular reactor (7 L) and reactor 1 L achieved 35.2 ± 0.2% and 28.3 ± 1%, respectively, indicating the effect of shape reactor. The FAs were affected by high light intensity, decreasing SFAs to 2.5%, and increased monounsaturated fatty acids + polyunsaturated fatty acids to 2.5%. PUFAs (20:5n-3) and (20:4n-3) were affected by reactor shape, decreasing by half in the tubular reactor. In the best culture, fed-batch tubular reactor (7 L) at 200 μmol E m⁻² s⁻¹ contains major FAs (16:0; 38.06 ± 0.16%), (16:1n-7; 30.74 ± 0.58%), and (18:1n-9; 17.15 ± 0.91%).     

Using icon arrays to communicate medical risks: Overcoming low numeracy.

Objective: Icon arrays have been suggested as a potentially promising format for communicating risks to patients—especially those with low numeracy skills—but experimental studies are lacking. This study investigates whether icon arrays increase accuracy of understanding medical risks, and whether they affect perceived seriousness of risks and helpfulness of treatments. Design: Two experiments were conducted on samples of older adults (n = 59, 62 to 77 years of age) and university students (n = 112, 26 to 35 years of age). Main Outcome Measures: Accuracy of understanding risk reduction; perceived seriousness of risks; perceived helpfulness of treatments. Results: Icon arrays increased accuracy of both low- and high-numeracy people, even when transparent numerical representations were used. Risks presented via icon arrays were perceived as less serious than those presented numerically. With larger icon arrays (1,000 instead of 100 icons) risks were perceived more serious, and risk reduction larger. Conclusions: Icon arrays are a promising way of communicating medical risks to a wide range of patient groups, including older adults with lower numeracy skills. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chelating,antioxidant and antiproliferative activity of <Emphasis Type="Italic">Vicia sativa</Emphasis> polyphenol extracts

The metal chelating activity, antioxidant properties, and the effect on cell growth of a polyphenol extract from Vicia sativa have been investigated, and compared to those of soybean. The extracts from V. sativa seeds contained three and five times more polyphenols and flavonoids than soybean, respectively. The soybean polyphenol extracts showed higher copper and iron chelating activity than those from V. sativa, although polyphenols from V. sativa were more effective in preventing β-carotene oxidation and showed higher reducing power and scavenging activity than soybean polyphenols. In addition, V. sativa polyphenols were toxic to THP-1 leukemic cells, as opposed to polyphenols extracted from soybean that did not show any antiproliferative activity at similar concentrations. In conclusion, V. sativa polyphenol extracts show promising antioxidant and antiproliferative activities that may be of interest from a functional point of view and for the revalorization of this ancient crop.