Effect of topical berberine in murine cutaneous leishmaniasis lesions

Objectives: More effective topical treatments remain an unmet need for the localized forms of cutaneous leishmaniasis (CL). The aim of this study was to evaluate the efficacy and safety of a topical berberine cream in BALB/c mice infected with Leishmania major parasites. Methods: A cream containing 0.5% berberine-β-glycerophosphate salt and 2.5% menthol was prepared. Its physicochemical and stability properties were determined. The cream was evaluated for its capacity to reduce lesion size and parasitic load as well as to promote wound healing after twice-a-day administration for 35 days. Clinical biochemical profile was used for estimating off-target effects. In vitro time-to-kill curves in L. major-infected macrophages and skin and plasma pharmacokinetics were determined, aiming to establish pharmacokinetic/pharmacodynamic relationships. Results: The cream was stable at 40°C for 3 months and at 4°C for at least 8 months. It was able to halt lesion progression in all treated mice. At the end of treatment, parasite load in the skin was reduced by 99.9% (4 log) and genes involved in the wound healing process were up-regulated compared with untreated mice. The observed effects were higher than expected from in vitro time-to-kill kinetic and plasma berberine concentrations, which ranged between 0.07 and 0.22 μM. Conclusions: The twice-a-day administration of a topical berberine cream was safe, able to stop parasite progression and improved the appearance of skin CL lesions. The relationship between drug plasma levels and in vivo effect was unclear

End-User Development of Voice User Interfaces based on Web content

Voice Assistants, and particularly the latest gadgets called smart speakers, allow end users to interact with applications by means of voice commands. As usual, end users are able to install applications (also called skills) that are available in repositories and fulfill multiple purposes. In this work we present an end-user environment to define skills for voice assistants based on the extraction of Web content and their organization into different voice navigation patterns. We describe the approach, the end-user development environment, and finally we present some case studies based on Alexa and Amazon Echo

Tomography analysis of Al–Mg alloys manufactured by wire-arc directed energy deposition with different metal transfer modes

The interest in aluminum-magnesium alloy additive manufacturing through Wire-arc Directed Energy Deposition (DED) technology has substantially grown in recent years. The main challenge in additive manufactured aluminum-magnesium alloys is the occurrence of porosity. In this context, Gas Metal Arc Welding (GMAW) based additive technology is suitable for aluminum printing as it allows high deposition rates and reduces porosity levels through alternative metal transfer modes without adding any extra equipment. Therefore, this research explores the effects of these alternative metal transfer modes, which determine the current signal shape and polarity, on the distribution and morphology of micropores using X-ray computed tomography in both single-bead and double-bead walls. The novelty of this paper lies in the comparison of the porosity obtained using alternative transfer modes, which, unlike CMT (Cold Metal Transfer) modes, have not been exhaustively analyzed. Additionally, to date, there has been no comprehensive comparison of the porosity results obtained in single walls and overlapped walls. The results demonstrate that pulsed-AC transfer mode with a current signal featuring variable polarity yields acceptable porosity fraction values of less than 0.04% in single-bead walls and less than 0.01% in double-bead walls, achieving high productivity

Web-Augmentation, Design Thinking, and Collaboration Engineering to Foster Innovation in DSS for Agriculture: A Case Study

International audienceDecision making in agriculture increasingly relies on software, for example to gather important information or to weight alternatives. Information systems innovation in agriculture is a challenging and very active area. Existing software products, frequently implemented as web applications, are found to lack functionality, for example to support collaboration. Aigmenting the web is a widely adopted technique for enhancing existing applications with new features which are not available out of the shelf. Design thinking has proven to be an effective tool to support innovation on many domains. Collaboration Engineering is an effective means to reuse design experience of collaboration strategies. This work presents an approach to involve end-users in enhancing existing web software to produce incremental innovations. The approach relies on Design Thinking, Web Augmenttion and Collaboration Engineering. The approcah was successfully tried in a case study letting end-users add collaboration support to a system that did not provide it

Parámetros reproductores de la gaviota patiamarilla Larus michahellis lusitanius Naumann, 1840 en Gipuzkoa

El objetivo del presente artículo es estudiar la reproducción de la gaviota patiamarilla Larus michahellis lusitanius Naumann, 1840 en Gipuzkoa. En particular, analizamos (1) el tamaño de puesta (número de huevos/nido), (2) la fecha de eclosión, (3) el número de huevos eclosionados/nido y (4) la proporción de huevos eclosionados en relación al número de huevos en el nido, considerando dos zonas que, a priori, presentan diferente tipo de sustrato de nidificación. Para ello, durante un periodo de 40 días (16.05.201124.06-2011) la colonia de Ulia se visitó a diario. En promedio, se registró un tamaño de puesta de 3 huevos/nido, un número de huevos eclosionados de 3/nido y un porcentaje de eclosión de 88,4%. La fecha media de eclosión sucedió en la segunda quincena de Mayo. Asimismo, se registraron algunas diferencias entre las dos zonas en que se dividió la colonia (tamaño de puesta inferior y porcentaje de huevos eclosionados superior en una zona que presentó más roca y vegetación de mayor porte en relación a otra zona con menos rocas así como más hierba). Discutimos esto en un contexto de zonificación de la colonia de estudio en el marco de áreas de carácter óptimo o subóptimo en términos reproductivos

Effect of topical berberine in murine cutaneous leishmaniasis lesions

Objectives: More effective topical treatments remain an unmet need for the localized forms of cutaneous leishmaniasis (CL). The aim of this study was to evaluate the efficacy and safety of a topical berberine cream in BALB/c mice infected with Leishmania major parasites. Methods: A cream containing 0.5% berberine-β-glycerophosphate salt and 2.5% menthol was prepared. Its physicochemical and stability properties were determined. The cream was evaluated for its capacity to reduce lesion size and parasitic load as well as to promote wound healing after twice-a-day administration for 35 days. Clinical biochemical profile was used for estimating off-target effects. In vitro time-to-kill curves in L. major-infected macrophages and skin and plasma pharmacokinetics were determined, aiming to establish pharmacokinetic/pharmacodynamic relationships. Results: The cream was stable at 40°C for 3 months and at 4°C for at least 8 months. It was able to halt lesion progression in all treated mice. At the end of treatment, parasite load in the skin was reduced by 99.9% (4 log) and genes involved in the wound healing process were up-regulated compared with untreated mice. The observed effects were higher than expected from in vitro time-to-kill kinetic and plasma berberine concentrations, which ranged between 0.07 and 0.22 μM. Conclusions: The twice-a-day administration of a topical berberine cream was safe, able to stop parasite progression and improved the appearance of skin CL lesions. The relationship between drug plasma levels and in vivo effect was unclear

Influence of alkyl chain length and structure on the extraction of copper(II) from aqueous acid by 5-alkyl-2-hydroxybenzaldoximes in hydrocarbon solvents: Diffusion coefficients of extractants and their complexes

Measurement of the kinetics of extraction of copper(II) by 19 different 5-alkyl-2-hydroxybenzaldoximes (alkyl is C7H15 and C9H19) from acidic (hydrogen sulfate buffer) aqueous solution in the range pH 3.4-2.0, into 20% v/v toluene in n-hexane is reported. The lowering of the interfacial tension has been measured in some cases. The solubility of the extractants in water has been measured spectrophotometrically. A modified Taylor-Aris dispersion technique has been used to measure the diffusion coefficients in n-hexane and Orfom SX7 of some of the extractants and of the copper(II) complexes which they form. At low initial bulk concentrations (<10 mol m(-3)) of the extractants, the rate of extraction is controlled by the rate of diffusion of the extractant from the bulk to the organic-aqueous interface. The diffusion coefficient is related to the steric bulk of the alkyl substituent. At higher initial bulk concentrations (200 mol m(-3)) of the extractants, when the interface is saturated, the rate of extraction is inversely related to the apparent steric bulk of the alkyl substituent. (C) 1999 Academic Press

Management practices for postdural puncture headache in obstetrics: a prospective, international, cohort study

© 2020 British Journal of AnaesthesiaBackground: Accidental dural puncture is an uncommon complication of epidural analgesia and can cause postdural puncture headache (PDPH). We aimed to describe management practices and outcomes after PDPH treated by epidural blood patch (EBP) or no EBP. Methods: Following ethics committee approval, patients who developed PDPH after accidental dural puncture were recruited from participating countries and divided into two groups, those receiving EBP or no EBP. Data registered included patient and procedure characteristics, headache symptoms and intensity, management practices, and complications. Follow-up was at 3 months. Results: A total of 1001 patients from 24 countries were included, of which 647 (64.6%) received an EBP and 354 (35.4%) did not receive an EBP (no-EBP). Higher initial headache intensity was associated with greater use of EBP, odds ratio 1.29 (95% confidence interval 1.19–1.41) per pain intensity unit increase. Headache intensity declined sharply at 4 h after EBP and 127 (19.3%) patients received a second EBP. On average, no or mild headache (numeric rating score≤3) was observed 7 days after diagnosis. Intracranial bleeding was diagnosed in three patients (0.46%), and backache, headache, and analgesic use were more common at 3 months in the EBP group. Conclusions: Management practices vary between countries, but EBP was more often used in patients with greater initial headache intensity. EBP reduced headache intensity quickly, but about 20% of patients needed a second EBP. After 7 days, most patients had no or mild headache. Backache, headache, and analgesic use were more common at 3 months in patients receiving an EBP