How Bees Respond Differently to Field Margins of Shrubby and Herbaceous Plants in Intensive Agricultural Crops of the Mediterranean Area

(1) Intensive agriculture has a high impact on pollinating insects, and conservation strategies targeting agricultural landscapes may greatly contribute to their maintenance. The aim of this work was to quantify the effect that the vegetation of crop margins, with either herbaceous or shrubby plants, had on the abundance and diversity of bees in comparison to non-restored margins. (2) The work was carried out in an area of intensive agriculture in southern Spain. Bees were monitored visually and using pan traps, and floral resources were quantified in crop margins for two years. (3) An increase in the abundance and diversity of wild bees in restored margins was registered, compared to non-restored margins. Significant differences in the structure of bee communities were found between shrubby and herbaceous margins. Apis mellifera and mining bees were found to be more polylectic than wild Apidae and Megachilidae. The abundance of A. mellifera and mining bees was correlated to the total floral resources, in particular, to those offered by the Boraginaceae and Brassicaceae; wild Apidae and Megachilidae were associated with the Lamiaceae. (4) This work emphasises the importance of floral diversity and shrubby plants for the maintenance of rich bee communities in Mediterranean agricultural landscapes

Clobazam Therapeutic Drug Monitoring: A Comprehensive Review of the Literature With Proposals to Improve Future Studies

Background: Clobazam was recently approved for Lennox–Gastaut syndrome in the United States. There is no published review article focused on clobazam therapeutic drug monitoring (TDM) in English. Methods: More than 200 clobazam articles identified by a PubMed search were carefully reviewed for information on clobazam pharmacokinetics. Clobazam is mainly metabolized by a cytochrome P450 (CYP) isoenzyme, CYP3A4, to its active metabolite, N-desmethylclobazam. Then, N-desmethylclobazam is mainly metabolized by CYP2C19 unless the individual has no CYP2C19 activity [poor metabolizer (PM)]. Results: Using a mechanistic approach to reinterpret the published findings of steady-state TDM and single-dosing pharmacokinetic studies, 4 different serum clobazam concentration ratios were studied. The available limited steady-state TDM data suggest that the serum N-desmethylclobazam/clobazam ratio can be useful for clinicians, including identifying CYP2C19 PMs (ratio \u3e25 in the absence of inhibitors). There are 3 possible concentration/dose (C/D) ratios. The clobazam C/D ratio has the potential to measure the contribution of CYP3A4 activity to the clearance of clobazam from the body. The N-desmethylclobazam C/D ratio does not seem to be a good measure of clobazam clearance and should be substituted with the total (clobazam + N-desmethylclobazam) C/D ratio. Conclusions: Future clobazam TDM studies need to use trough concentrations after steady state has been reached (\u3e3 weeks in normal individuals and several months in CYP2C19 PMs). These future studies need to explore the potential of clobazam and total C/D ratios. Better studies on the relative potency of N-desmethylclobazam compared with the parent compound are needed to provide weighted total serum concentrations that correct for the possible lower N-desmethylclobazam pharmacodynamic activity. Standardization and more studies of C/D ratios from clobazam and other drugs can be helpful to move TDM forward

Drug Dosage Individualization Based on a Random-Effects Linear Model

This article investigates drug dosage individualization when the patient population can be described with a random-effects linear model of a continuous pharmacokinetic or pharmacodynamic response. Specifically, we show through both decision-theoretic arguments and simulations that a published clinical algorithm may produce better individualized dosages than some traditional methods of therapeutic drug monitoring. Since empirical evidence suggests that the linear model may adequately describe drugs and patient populations, and linear models are easier to handle than the nonlinear models traditionally used in population pharmacokinetics, our results highlight the potential applicability of linear mixed models to dosage computations and personalized medicine

Callus culture for biomass production of milk thistle as a potential source of milk clotting peptidases

The objective of this work was the optimization of the conditions of in vitro culture for callus production of Silybum marianum (L.) Gaertn. (Asteraceae). Sections of cotyledons, previously disinfected by washing successively with ethanol 70º, NaClO (10% w/v) and Tween 20 (0.05% v/v) and rinsing with sterile distilled water, were used as explants. For its initial culture, B5 medium supplemented with BA and 2,4-D solidified with phytagel was used, and a 63% survival was achieved. To obtain callus, two solid media were assayed (S1 and S2) using B5 medium supplemented with growth regulators (BA and 2,4-D or NAA and BA, respectively). The calli were grown at 25ºC during 45 days in darkness. Growth kinetics was studied using S1 medium obtaining a typical growth curve with an exponential phase after 14 days of incubation (rate of growth 0.005 g dry weight/ day) and stationary phase after 35 days. The rate of growth in S2 medium was slower, and rhizogenesis was observed starting on the fifth week of incubation. From these results, the best culture medium for callus production of Silybum marianum was S1 medium.Facultad de Ciencias Exacta

Callus culture for biomass production of milk thistle as a potential source of milk clotting peptidases

The objective of this work was the optimization of the conditions of in vitro culture for callus production of Silybum marianum (L.) Gaertn. (Asteraceae). Sections of cotyledons, previously disinfected by washing successively with ethanol 70º, NaClO (10% w/v) and Tween 20 (0.05% v/v) and rinsing with sterile distilled water, were used as explants. For its initial culture, B5 medium supplemented with BA and 2,4-D solidified with phytagel was used, and a 63% survival was achieved. To obtain callus, two solid media were assayed (S1 and S2) using B5 medium supplemented with growth regulators (BA and 2,4-D or NAA and BA, respectively). The calli were grown at 25ºC during 45 days in darkness. Growth kinetics was studied using S1 medium obtaining a typical growth curve with an exponential phase after 14 days of incubation (rate of growth 0.005 g dry weight/ day) and stationary phase after 35 days. The rate of growth in S2 medium was slower, and rhizogenesis was observed starting on the fifth week of incubation. From these results, the best culture medium for callus production of Silybum marianum was S1 medium.Facultad de Ciencias Exacta

Parametric macromodeling of integrated inductors for RF circuit design

Nowadays, parametric macromodeling techniques are widely used to describe electromagnetic structures. In this contribution, the application of such parametric macromodeling techniques to the design of integrated inductors and radio-frequency circuit design is investigated. In order to allow such different operations, a new modeling methodology is proposed, which improves the modeling accuracy when compared to former techniques. The new methodology is tailored to the unique characteristics of the devices under study. The obtained parametric macromodel is then used in a synthesis methodology and in the design of a voltage controlled oscillator in a 0.35-μm CMOS technologyMinisterio de Economía y Competitividad TEC2013-45638-C3- 3-RJunta de Andalucía P12-TIC-148

Perfil neurohormonal de pacientes reumáticos con insuficiencia aórtica crónica severa

FUNDAMENTO: Os neuro-hormônios estão envolvidos na fisiopatologia da insuficiência cardíaca, mas pouco se sabe sobre seu comportamento na insuficiência aórtica crônica importante (IAo). OBJETIVO: Analisar o comportamento desses mediadores na IAo. MÉTODOS: Analisamos 89 pacientes com IAo, com média etária de 33,6±11,5 anos, 84,6% do sexo masculino, 60% assintomáticos, todos de etiologia reumática. Após avaliação clínica e ecocardiográfica, realizaram-se dosagens plasmáticas de fator de necrose tumoral (TNF), seus antagonistas receptores solúveis tipos I e II (sTNFRI e sTNFRII), interleucina-6 (IL-6), seu receptor solúvel, endotelina-1 e peptídeo natriurético tipo B (BNP). Doze indivíduos saudáveis serviram como controle. RESULTADOS: O valor médio de diâmetro diastólico (DD) do ventrículo esquerdo (VE) foi de 71,9±8,3 mm, e o do diâmetro sistólico (DS) do VE, de 50,4±9,3 mm. Os níveis de neuro-hormônios estavam elevados nos pacientes com IAo: TNF 92,65±110,24 pg/ml vs. 1,67±1,21 pg/ml nos controles, p<0,001; IL-6 7,17±7,78 pg/ml vs. 0,81±0,38 pg/ml nos controles, p = 0,0001; e TNFRI 894,75±348,87 pg/ml vs. 521,42±395,13 pg/ml, p = 0,007. Com exceção dos níveis de BNP, os pacientes sintomáticos e assintomáticos apresentaram perfil neuro-hormonal semelhante. Houve correlação entre TNFRII e diâmetro diastólico do ventrículo esquerdo (DDVE) (r = -0,329, p = 0,038) e diâmetro sistólico do ventrículo esquerdo (DSVE) (r = -0,352, p = 0,027). Os níveis de BNP estavam significativamente mais altos em pacientes sintomáticos, e apenas nestes foi possível correlação entre BNP e diâmetros ventriculares. CONCLUSÃO: Pacientes com insuficiência aórtica crônica importante apresentam altos níveis neuro-hormônios, sem correlação com o status sintomático. Os níveis de TNFRII e BNP puderam ser correlacionados com diâmetros ventriculares, mas apenas este último com sintomas.BACKGROUND: Neurohormones are involved in the physiopathology of heart failure, but little is known about its behavior in significant chronic aortic regurgitation (AR). We aimed at analyzing the behavior of these mediators in AF. OBJECTIVE: We aimed at analyzing the behavior of these mediators in AF. METHODS: We analyzed 89 patients with AF, whose mean age was 33.6±11.5 years and of whom 84.6% were males, 60% asymptomatic, all with rheumatic etiology. After the clinical and echocardiographic assessment, plasma measurements of tumor necrosis factor (TNF), soluble TNF receptor types I and II (sTNFRI e sTNFRII), interleukin-6 (IL-6), its soluble receptor (sIL6R), endothelin-1 and B-type natriuretic peptide (BNP) were carried out; 12 healthy individuals were used as controls. RESULTS: The mean values of the left ventricle diastolic diameter (LVDD) were 71.9±8.3mm, whereas the mean values of the LV systolic diameter (LVSD) were 50.4±9.3mm. The neurohormonal levels were elevated in patients with AF (TNF 92.65±110.24 pg/mL vs. 1.67±1.21 pg/ml in controls, p<0.001), (IL-6 7.17±7.78pg/ml vs. 0.81±0.38pg/mL in controls, p=0.0001) and TNFRI (894.75±348.87pg/mL vs. 521.42±395.13pg/ml, p=0.007). Except for the BNP levels, symptomatic and asymptomatic patients presented a similar neurohormonal profile. There was a correlation between TNFRII and LVDD (r=-0.329, p=0.038) and LVSD (r=-0.352, p=0.027). BNP levels were significantly higher in symptomatic patients and only in the latter it was possible to establish a correlation between BNP and ventricular diameters. CONCLUSION: Patients with significant chronic AF present high neurohormonal levels, with no correlation with the symptomatic status. The TNFRII and BNP levels could be correlated with ventricular diameters, but only the latter could be correlated with symptoms.FUNDAMENTO: Las neurohormonas están involucradas en la fisiopatología de la insuficiencia cardiaca, pero poco se sabe sobre su comportamiento en la insuficiencia aórtica crónica severa (IAo severa). OBJETIVO: Analizar el comportamiento de estos mediadores en la IAo severa. MÉTODOS: Analizamos a 89 pacientes con IAo severa, con un promedio de edad de 33,6±11,5 años, el 84,6% del sexo masculino, el 60% asintomáticos, todos de etiología reumática. Después de una evaluación clínica y ecocardiográfica, se realizaron dosificaciones plasmáticas de factor de necrosis tumoral (TNF), sus antagonistas receptores solubles tipos I y II (sTNFRI y sTNFRII), interleucina-6 (IL-6), su receptor soluble, endotelina-1 y péptido natriurético tipo B (BNP). Un grupo de 12 individuos saludables sirvieron como control. RESULTADOS: El valor promedio de diámetro diastólico (DD) del ventrículo izquierdo (VI) fue de 71,9±8,3 mm, y el del diámetro sistólico (DS) del VI, de 50,4±9,3 mm. Los niveles de neurohormonas estaban elevados en los pacientes con IAo severa: TNF 92,65±110,24 pg/ml vs 1,67±1,21 pg/ml en los controles, p<0,001; IL-6 7,17±7,78 pg/ml vs 0,81±0,38 pg/ml en los controles, p<0,0001; y TNFRI 894,75±348,87 pg/ml vs 521,42±395,13 pg/ml, p = 0,007. Con excepción de los niveles de BNP, los pacientes sintomáticos y asintomáticos presentaron perfil neurohormonal similar. Se registró una correlación entre el TNFRII y el diámetro diastólico del ventrículo izquierdo (DDVI) (r = -0,329, p = 0,038) y el diámetro sistólico del ventrículo izquierdo (DSVI) (r = -0,352, p = 0,027). Los niveles de BNP se presentaban significativamente más altos en pacientes sintomáticos, y sólo en ellos fue posible una correlación entre BNP y los diámetros ventriculares. CONCLUSIÓN: Pacientes con insuficiencia aórtica crónica severa presentan altos niveles de neurohormonas, sin correlación con el status sintomático. Los niveles de TNFRII y BNP se pudieron correlacionar con los diámetros ventriculares, pero sólo este último con síntomas.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Callus culture for biomass production of milk thistle as a potential source of milk clotting peptidases

The objective of this work was the optimization of the conditions of in vitro culture for callus production of Silybum marianum (L.) Gaertn. ( Asteraceae) . Sections of cotyledons, previously disinfected by washing successively with ethanol 70\ub0, NaClO (10% w/v) and Tween 20 (0.05% v/v) and rinsing with sterile distilled water, were used as explants. For its initial culture, B5 medium supplemented with BA and 2,4-D solidified with phytagel was used, and a 63% survival was achieved. To obtain callus, two solid media were assayed (S1 and S2) using B5 medium supplemented with growth regulators (BA and 2,4-D or NAA and BA, respectively). The calli were grown at 25\ub0C during 45 days in darkness. Growth kinetics was studied using S1 medium obtaining a typical growth curve with an exponential phase after 14 days of incubation (rate of growth 0.005 g dry weight/ day) and stationary phase after 35 days. The rate of growth in S2 medium was slower, and rhizogenesis was observed starting on the fifth week of incubation. From these results, the best culture medium for callus production of Silybum marianum was S1 medium

Callus culture for biomass production of milk thistle as a potential source of milk clotting peptidases

The objective of this work was the optimization of the conditions of in vitro culture for callus production of Silybum marianum (L.) Gaertn. ( Asteraceae ). Sections of cotyledons, previously disinfected by washing successively with ethanol 70\ub0, NaClO (10% w/v) and Tween 20 (0.05% v/v) and rinsing with sterile distilled water, were used as explants. For its initial culture, B5 medium supplemented with BA and 2,4-D solidified with phytagel was used, and a 63% survival was achieved. To obtain callus, two solid media were assayed (S1 and S2) using B5 medium supplemented with growth regulators (BA and 2,4-D or NAA and BA, respectively). The calli were grown at 25\ub0C during 45 days in darkness. Growth kinetics was studied using S1 medium obtaining a typical growth curve with an exponential phase after 14 days of incubation (rate of growth 0.005 gdry weight/ day) and stationary phase after 35 days. The rate of growth in S2 medium was slower, and rhizogenesis was observed starting on the fifth week of incubation. From these results, the best culture medium for callus production of Silybum marianum was S1 medium