Synthesis, leishmanicidal, trypanocidal and cytotoxic activities of quinoline-chalcone and quinoline-chromone hybrids

We report herein the synthesis and biological activities (cytotoxicity, leishmanicidal and trypanocidal) of six quinoline-chalcone and five quinoline-chromone hybrids. The synthesized compounds were evaluated against amastigotes forms of Leishmania (V) panamensis, which is the most prevalent Leishmania species in Colombia and Trypanosoma cruzi, which is the major pathogenic species to humans. Cytotoxicity was evaluated against human U-937 macrophages. Compounds 8–12, 20, 23 and 24 showed activity against Leishmania (V) panamensis, while compounds 9, 10, 12, 20 and 23 had activity against Trypanosoma cruzi with EC50 values lower than 18 mg mL−1. 20 was the most active compound for both Leishmania (V) panamensis and Trypanosoma cruzi with EC50 of 6.11 ± 0.26 μg mL−1 (16.91 μM) and 4.09 ± 0.24 (11.32 μM), respectively. All hybrids compounds showed better activity than the anti-leishmanial drug meglumine antimoniate. Compounds 20 and 23 showed higher activity than benznidazole, the current anti-trypanosomal drug. Although these compounds showed toxicity for mammalian U-937 cells,they still have the potential to be considered as candidates to antileishmanial or trypanocydal drug development

Measuring color differences in gonioapparent materials used in the automotive industry

This paper illustrates how to design a visual experiment to measure color differences in gonioapparent materials and how to assess the merits of different advanced color-difference formulas trying to predict the results of such experiment. Successful color-difference formulas are necessary for industrial quality control and artificial color-vision applications. A color- difference formula must be accurate under a wide variety of experimental conditions including the use of challenging materials like, for example, gonioapparent samples. Improving the experimental design in a previous paper [Melgosaet al., Optics Express 22, 3458-3467 (2014)], we have tested 11 advanced color-difference formulas from visual assessments performed by a panel of 11 observers with normal colorvision using a set of 56 nearly achromatic colorpairs of automotive gonioapparent samples. Best predictions of our experimental results were found for the AUDI2000 color-difference formula, followed by color-difference formulas based on the color appearance model CIECAM02. Parameters in the original weighting function for lightness in the AUDI2000 formula were optimized obtaining small improvements. However, a power function from results provided by the AUDI2000 formula considerably improved results, producing values close to the inter-observer variability in our visual experiment. Additional research is required to obtain a modified AUDI2000 color-difference formula significantly better than the current one.This research was supported by the Ministry of Economy and Competitiveness of Spain, research projects FIS2013-40661-P and DPI2011-30090-C02, with European Research Development Fund (ERDF), as well as by the National Science Foundation of China (grant number 61178053)

The Harvey–Bradshaw Index adapted to a mobile application compared with In-clinic assessment: the MediCrohn Study

[Abstract] Objectives: Mobile apps are useful tools in e-health and self-management strategies in disease monitoring. We evaluated the Harvey–Bradshaw index (HBI) mobile app self-administered by the patient to see if its results agreed with HBI in-clinic assessed by a physician. Methods: Patients were enrolled in a 4-month prospective study with clinical assessments at months 1 and 4. Patients completed mobile app HBI and within 48 h, HBI was performed by a physician (gold standard). HBI scores characterized Crohn's disease (CD) as remission <5 or active ≥5. We determined agreement per item and total HBI score and intraclass correlation coefficients (ICCs). Bland–Altman plot was performed. HBI changes in disease activity from month 1 to month 4 were determined. Results: A total of 219 patients were enrolled. All scheduled assessments (385 pairs of the HBI questionnaire) showed a high percentage of agreement for remission/activity (92.4%, κ = 0.796), positive predictive value (PPV) for remission of 98.2%, and negative predictive value of 76.7%. High agreement was also found at month 1 (93.15%, κ = 0.82) and month 4 (91.5%, κ = 0.75). Bland–Altman plot was more uniform when the HBI mean values were <5 (remission). ICC values were 0.82, 0.897, and 0.879 in all scheduled assessments, 1 and 4 months, respectively. Conclusions: We found a high percentage of agreement between patients' self-administered mobile app HBI and in-clinic physician assessment to detect CD activity with a remarkably high PPV for remission. The mobile app HBI might allow a strict control of inflammation by remote monitoring and flexible follow-up of CD patients. Reduction of sanitary costs could be possible

A new diffuse luminous efficacy model for daylight availability in Burgos, Spain

The determination of optimal illumination conditions in buildings is of great interest both for reducing energy consumption and for exploiting solar resources with greater efficiency and sustainability. The most commonplace method of estimating daylight is the luminous efficacy approach, using the more widely measured solar irradiance. In this present study, a new model of diffuse luminous efficacy over a horizontal surface is proposed. A comparative study of twenty-two classic models is presented, to obtain diffuse illuminance, using both, the original mathematical models and the adapted models with local coefficients, in order to determine the most suitable models for Burgos, a city located in north-western Spain. With this purpose in mind, twelve models are selected for all sky conditions, five models for modelling clear sky, two for partly cloudy sky, and three for overcast sky. These twenty-two models are then compared with the new model both for all sky conditions and for particular sky conditions (clear, partly cloudy, and overcast). The behaviour of the new model showed greater accuracy than most of the classic models under analysis. Hence, the advantage of the diffuse luminous efficacy model that can be applied both to all sky and to particular sky conditions.Spanish Government (Ministerio de Economía y Competitividad) (ENE2014-54601-R). David González Peña would also like to thank the Junta de Castilla-León for economic support (PIRTU Program, ORDEN EDU/310/2015)

The Zoning of Semi-Enclosed Bodies of Water According to the Sediment Pollution: The Bay of Algeciras as a Case Example

This paper reports a study of the occurrence and levels of polycyclic aromatic hydrocarbons (PAHs) in a bay characterised by a chronic persistent impact. A total of 55 sediment samples were taken at different depths up to 111 m in two sampling campaigns. Chemical analyses were carried out by gas chromatography-mass spectroscopy. The results indicate that: (1) significant spatial variations exist, (2) levels of PAHs are related more strongly to the spatial distribution of sediments than to mineralogy/granulometry, (3) the sediments are slightly-to-moderately contaminated by PAHs, and (4) these PAHs derive from pyrolytic and petrogenic sources. Through use of an innovative data classification system (proposed according to depth and spatial location of sampling points), and using factorial and cluster techniques, five zones have been differentiated depending on the contamination level and source

Low-Dose Amphotericin B and Murine Dialyzable Spleen Extracts Protect against SystemicCandidaInfection in Mice

Candida albicans causes opportunistic systemic infections with high mortality (30%–50%). Despite significant nephrotoxicity, amphotericin (AmB) is still used for the treatment of this serious fungal infection. Therefore, alternative treatments are urgently needed. Dialyzable leukocyte extracts have been used successfully to treat patients with mucocutaneous candidiasis, but their effectiveness in systemic candidiasis has not been evaluated. In this study, low-dose AmB (0.1 mg/kg) plus 10 pg of murine dialyzable spleen extracts (mDSE) were tested in a systemic candidiasis mouse model. Survival, tissue fungal burden, kidney damage, kidney cytokines, and serum levels of IL-6 and hepcidin were evaluated. Our results showed that the combined treatment of low-dose AmB plus mDSE improved survival and reduced kidney fungal burden and histopathology; these effects correlated with increased kidney concentration of IFN-γ and TGF-β1, decreased levels of TNF-α, IL-6, and IL-10, as well as high levels of systemic IL-6 and hepcidin. Low-dose AmB and mDSE synergized to clear the infectious agent and reduced tissue damage, confirming the efficacy of a low dose of AmB, which might decrease the risk of drug toxicity. Further studies are necessary to explore these findings and its implications in future therapeutic approaches

PDGF-BB serum levels are decreased in adult onset Pompe patients

Adult onset Pompe disease is a genetic disorder characterized by slowly progressive skeletal and respiratory muscle weakness. Symptomatic patients are treated with enzymatic replacement therapy with human recombinant alfa glucosidase. Motor functional tests and spirometry are commonly used to follow patients up. However, a serological biomarker that correlates with the progression of the disease could improve follow-up. We studied serum concentrations of TGFβ, PDGF-BB, PDGF-AA and CTGF growth factors in 37 adult onset Pompe patients and 45 controls. Moreover, all patients performed several muscle function tests, conventional spirometry, and quantitative muscle MRI using 3-point Dixon. We observed a statistically significant change in the serum concentration of each growth factor in patients compared to controls. However, only PDGF-BB levels were able to differentiate between asymptomatic and symptomatic patients, suggesting its potential role in the follow-up of asymptomatic patients. Moreover, our results point to a dysregulation of muscle regeneration as an additional pathomechanism of Pompe disease

Exploring genetic resistance to infectious salmon anaemia virus in Atlantic salmon by genome-wide association and RNA sequencing

Funding The authors gratefully acknowledge funding from BBSRC (BB/R008612/1, BB/R008973/1), in addition to BBSRC Institute Strategic Programme Grants to the Roslin Institute (BB/P013759/1 and BB/P013740/1).Peer reviewedPublisher PD