Cyclopenta[d]pyrimidines and dihydropyrrolo[2,3-d]pyrimidines as potent and selective corticotropin-releasing factor 1 receptor antagonists

Two new classes of potent and selective CRF(1) receptor antagonists are presented. Exploration of general templates 3 and 4 through modifications of the top amine and bottom phenyl substituents led to optimization of the in vitro affinity and pharmacokinetic profiles. The typical alkyl chains present in the top region of CRF(1) antagonists were replaced by substituted heteroaryl moieties, leading to a dramatic improvement of the metabolic stability. This improvement was apparent when the compounds were dosed in vivo: several compounds exhibited low plasma clearance, good oral bioavailability, and high brain penetration. As a consequence of their outstanding pharmacokinetic profiles, these CRF(1) antagonists, as exemplified by compound 4 fi (4-(4-bromo-3-methyl-1H-pyrazol-1-yl)-7-(2,4-dichlorophenyl)-2-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine), produced a dose-dependent "anxiolytic-like" effect when administered orally, decreasing the vocalization of rat pups.     

Markov model assessment of subjects' clinical skill using the E-Pelvis physical simulator

Inherent difficulties evaluating clinical competence of physicians has led to the widespread use of subjective skill assessment techniques. Inspired by an analogy between spoken language and surgical procedure, a generalized methodology using Markov models (MMs), independent of the modality under study, was developed. The methodology applied to an endoscopic experiment in "Generalized approach for modeling minimally invasive surgery as a stochastic process using a discrete Markov model" by J. Rosen et al. (IEEE Trans. Biomed. Eng., Vol. 53, No. 3, pp. 399-413, Mar. 2006) is modified and applied to data collected with the E-Pelvis physical simulator. The simulator incorporates five contact pressure sensors located in key anatomical landmarks. Two 32-state fully connected MMs are used, one for each skill level. Each state corresponds to a unique five-dimensional signature of contact pressures. Statistical distances measured between models representing subjects with different skill levels are sensitive enough to provide an objective measure of medical skill level. The method was tested with 41 expert subjects and 41 novice subjects in addition to the 30 subjects used for training the MM. Of the 82 subjects, 76 (92%) were classified correctly. Unique state transitions as well as pressure magnitudes for corresponding states were found to be skill dependent. The "white box" nature of the model provides insight into the examination process performed.     

Production and characterization of membranes of recycled waste materials: Cellulose acetate,obtained from sugarcane bagasse with polystyrene from plastics cups

Membranes of cellulose acetate from sugarcane bagasse (CA), as well as blends of this cellulose acetate and polystyrene from plastic cups (CA/PS) were produced by casting utilizing dichloromethane as solvent at the concentration 12% w/w. The membranes were characterized regarding ion diffusion by dialysis and properties of pure water permeation rate, PEG rejection (utilizing an aqueous solution 1% w/v of polyethylene glycol (PEG), 45 and 80 kDa). Thermal characterization by thermogravimetric analysis and differential scanning calorimetry were also performed. The morphology of the membranes' cross‐sections was evaluated by scanning electron microscopy. The experiment of ion diffusion by dialysis showed that the ion diffusion coefficient of CA membrane is comparable to that found in the literature for membranes of commercial cellulose triacetate, 8.47 × 10^?8 cm² s^?1, while the ion diffusion coefficient of blends decreased as PS was added to the system. Regarding transport driven by pressure, CA membrane presented low rejection of PEG 80 kDa. These results showed that CA membrane could be used in a range of application comprehending the process of ultrafiltration or microfiltration. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers.     

Mucilage microcosms

In the summers of 2000, 2001 and 2002, large amounts of sticky mucilaginous material aggregated to form masses of impressive dimensions over large areas of the Adriatic Sea, particularly in its northern part. Aggregates differing in size were sampled by SCUBA divers and submitted to chemical (nutrient and organic matter concentrations) and biological analysis (virus, bacteria and phytoplankton abundances and bacterial metabolism). Suspended and sinking mucilaginous aggregates were biota-rich environments where the abundance of planktonic organisms and the concentration of nutrients were orders of magnitude higher than in the surrounding seawater. The embedded phytoplankton was mostly composed of diatoms, but the dinoflagellate Gonyaulax fragilis, previously reported in association with the aggregates, was also present. A variety of processes occurred within the mucilaginous aggregates which resulted in the transformation of the organic matter composition and lability and contributed to a partial degradation of mucilage. For an efficient degradation of mucilage, several conditions are necessary: high bacterial abundance and activity and an efficient recycling of nutrients within the aggregates. Most of these conditions, appear to change depending on the type and age of the aggregate. During the first phase of aggregation (cobwebs and ribbons), bacterial activities addressed the degradation of organic matter, particularly that of the nitrogen fraction. The degradation products were rapidly taken up by bacteria, supporting an increase in their abundance and production. In aged mucilage (clouds), the degradation processes decreased and the bacterial metabolism suggested the presence of new organic labile compounds probably due to phytoplankton production. On the basis of our results, stringers, generally considered the first step of the aggregation process, seemed to be the result of a mechanical disruption of other types of aggregates.     

Climate change and the health impact of aflatoxins exposure in Portugal – an overview

Climate change has been indicated as a driver for food safety issues worldwide, mainly due to the impact on the occurrence of food safety hazards at various stages of food chain. Mycotoxins, natural contaminants produced by fungi, are among the most important of such hazards. Aflatoxins, which have the highest acute and chronic toxicity of all mycotoxins, assume particular importance. A recent study predicted aflatoxin contamination in maize and wheat crops in Europe within the next 100 years and aflatoxin B1 is predicted to become a food safety issue in Europe, especially in the most probable scenario of climate change (+2°C). This review discusses the potential influence of climate change on the health risk associated to aflatoxins dietary exposure of Portuguese population. We estimated the burden of disease associated to the current aflatoxin exposure for Portuguese population in terms of Disability Adjusted Life Years (DALYs). It is expected that in the future the number of DALYs and the associated cases of hepatocellular carcinoma due to aflatoxins exposure will increase due to climate change. The topics highlighted through this review, including the potential impact on health of the Portuguese population through the dietary exposure to aflatoxins, should represent an alert for the potential consequences of an incompletely explored perspective of climate change. Politics and decision-makers should be involved and committed to implement effective measures to deal with climate change issues and to reduce its possible consequences. This review constitutes a contribution for the prioritisation of strategies to face the unequal burden of effects of weather-related hazards in Portugal and across Europe.     

Effect of Vitamin D3 Fortification and Saskatoon Berry Syrup Addition on the Flavor Profile,Acceptability, and Antioxidant Properties of Rooibos Tea (Aspalathus linearis)

The unique characteristics and healthful reputation of caffeine‐free rooibos tea (RT) make it an ideal carrier for vitamin D₃ supplementation, and a potential base for the addition of Saskatoon berry syrup (SBS), a natural flavor additive. The objective of this study was to determine the effect of vitamin D₃ fortification and SBS addition on the flavor profile, consumer acceptability, and antioxidant properties of RT. Six formulations (RT, RT with SBS, RT with SBS and vitamin D₃, RT with vitamin D₃, green tea [GT], and GT with SBS) were evaluated by 12 trained panelists and 114 consumers. The formulations were also assessed for antioxidant capacity, physical characteristics, and untargeted phytochemical content. Sensory results revealed that the mean intensity values for berry and sweet attributes were significantly higher (P < 0.05) while bitter and astringent attributes were significantly lower when SBS was added to RT samples compared to those without syrup. Acceptability of flavor, aftertaste, and overall acceptability were also significantly higher for the RT with SBS. The addition of SBS to RT significantly increased the antioxidant capacities which may increase the related health benefits of RT. SBS contributed several polyphenols, particularly flavonoids, to the tea. Vitamin D₃ added to RT formulations did not significantly affect the sensory attributes, acceptability, or antioxidant content. For the development of a functional vitamin D₃ fortified iced‐tea beverage that can be consumed as part of the daily diet, SBS could be a favorable flavoring additive that may provide additional health benefits.