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Current asthma guidelines recommend stepping down controller treatment when the condition is well-controlled for a certain time. However, the optimal step-down strategy for well-controlled patients receiving a low-dose inhaled corticosteroid (ICS) with a long-acting β -agonist (LABA) remains unclear. This study was a randomized, open-label, three-arm, parallel pragmatic trial comparing two kinds of step-down approaches for maintaining treatment. Adults with asthma who were aged 18 years or older, and who had been stable with low-dose ICS/LABA for at least 3 months, were enrolled. Subjects (n= 225) were randomly allocated into one of three groups (maintaining low-dose ICS/LABA [G1], discontinuing LABA [G2], and reducing ICS/LABA to once daily [G3]), and were observed for 6 months. The primary end point was a change in Asthma Control Test (ACT) scores between randomization and the final 6-month follow-up. The change in ACT was analyzed in the per-protocol population; noninferiority was not demonstrated in either step-down group compared with the maintenance group (95% confidence interval of the difference, G2 vs G1= -1.40-0.55; G3 vs G1= -1.19-0.77). Although over 90% of patients were fine, higher rates of treatment failure were observed in step-down groups (G1 0%; G2 9.46%; and G3 9.09%; P= .027). There were no significant differences between step-down approaches in terms of ACT change or treatment failure. Both step-down methods were not noninferior to maintenance of treatment. Step-down therapy can be attempted when patients are stable, but appropriate monitoring and supervision are necessary with precautions regarding loss of disease control. Both step-down methods were not noninferior to maintenance of treatment. Step-down therapy can be attempted when patients are stable, but appropriate monitoring and supervision are necessary with precautions regarding loss of disease control. Quaternary ammonium compounds (QACs) are used extensively for cleaning and disinfection and have been documented in scattered reports as a cause of occupational asthma (OA) through bronchoprovocation tests (BPTs). To examine the clinical, functional, and inflammatory profile of QAC-induced OA compared with OA caused by other low-molecular weight (LMW) agents. The study was conducted in a retrospective multicenter cohort of 871 subjects with OA ascertained by a positive BPT. Subjects with QAC-induced OA (n= 22) were identified based on a positive BPT to QACs after exclusion of those challenged with cleaning products or disinfectants that contained other potential respiratory sensitizers. They were compared with 289 subjects with OA caused by other LMW agents. Most subjects with QAC-induced OA were working in the health care sector (n= 14). A twofold or greater increase in the postchallenge level of nonspecific bronchial hyperresponsiveness was recorded in eight of 11 subjects with QAC-induced OA (72.7%) and in 49.7% of those with OA caused by other LMW agents. Although sputum assessment was available in only eight subjects with QAC-induced OA, they showed a significantly greater median (interquartile) increase in sputum eosinophils (18.1% [range, 12.1% to 21.1%]) compared with those with OA caused by other LMW agents (2.0% [range, 0% to 5.2%]; P < .001). This study indicates that QAC-induced OA is associated with a highly eosinophilic pattern of airway response and provides further evidence supporting the sensitizing potential of QACs. The findings highlight the heterogeneous nature of the pathobiologic pathways involved in OA caused by LMW agents. This study indicates that QAC-induced OA is associated with a highly eosinophilic pattern of airway response and provides further evidence supporting the sensitizing potential of QACs. The findings highlight the heterogeneous nature of the pathobiologic pathways involved in OA caused by LMW agents.Bacterial wilt caused by the soil-borne plant pathogen Ralstonia solanacearum is a devastating disease worldwide. Upon plant colonization, R. solanacearum replicates massively, causing plant wilting and death; collapsed infected tissues then serve as a source of inoculum. In this work, we show that the plant metabolic pathway mediated by pyruvate decarboxylases (PDCs) contributes to plant tolerance to bacterial wilt disease. Arabidopsis and tomato plants respond to R. solanacearum infection by increasing PDC activity, and plants with deficient PDC activity are more susceptible to bacterial wilt. Treatment with either pyruvic acid or acetic acid (substrate and product of the PDC pathway, respectively) enhances plant tolerance to bacterial wilt disease. https://www.selleckchem.com/products/Nolvadex.html An effector protein secreted by R. solanacearum, RipAK, interacts with PDCs and inhibits their oligomerization and enzymatic activity. Collectively, our work reveals a metabolic pathway involved in plant resistance to biotic and abiotic stresses, and a bacterial virulence strategy to promote disease and the completion of the pathogenic life cycle. Nanoparticles (Np) can increase drug efficacy and overcome problems associated with solubility and aggregation in a solution of PpIX. Evaluate if Np interferes in the photophysical and photobiological capacity of the PpIX comparing with free PpIX intended for topical PDT of melanoma. In vitro photophysical evaluation of Np-PpIX was carried out through singlet oxygen ( O ) quantum yield. In vitro cytotoxicity and phototoxicity assays have used murine melanoma cell culture. The quantum yield of singlet oxygen has shown that Np did not influence the formation capacity of this reactive species. In the dark, all PpIX-Nps concentrations were less cytotoxic compared to free drugs. At a higher light dose (1500 mJ.cm ) 3.91 μg / mL PpIX had similar % viable cells for free and Np (∼34 %) meaning Nps did not interfere in the photodynamic effect of PpIX. However, at 7.91 μg / mL the phototoxicity increased for both (5.8 % viable cells for free versus 21.7 % for Nps). Despite the higher phototoxicity of free PpIX at this concentration, greater cytotoxicity in the dark was obtained (∼49 % viable cells for free versus ∼90.6 % Np) which means Nps protect the tumor tissue from the photodynamic action of PpIX. Np is a potential delivery system for melanoma skin cancer, since it maintained the photophysical properties of PpIX and excellent in vitro phototoxicity effect against melanoma cells, reducing cell viability ∼80 % (7.91 μg / mL PpIX in Nps) and provides safe PDT (due to lower cytotoxicity in the dark). Np is a potential delivery system for melanoma skin cancer, since it maintained the photophysical properties of PpIX and excellent in vitro phototoxicity effect against melanoma cells, reducing cell viability ∼80 % (7.91 μg / mL PpIX in Nps) and provides safe PDT (due to lower cytotoxicity in the dark).
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