Optimization of enzymatic parameters for the production of formononetin from red clover (Trifolium pratense L.) through a response surface methodology.

Trifolium pratense, is a forage found worldwide, but it is negatively impacted by the clover root borer, Hylastinus obscurus. Methanolic extraction has been reported for isolating formononetin from vegetal tissues, with an antifeeding effect on H. obscurus. However, this methodology is time-consuming and also extracts other secondary metabolites, whereas enzymatic assays can provide higher specificity. Hence, the objective of this work was to determine the optimal conditions in pH, temperature, and incubation time for the activity of isoflavone synthase via a response surface model. Once these parameters were optimized, the concentration of formononetin in cultivars and experimental lines of T. pratense was evaluated enzymatically. The results showed that the best condition for developing the enzymatic assay was pH 9.1 with an incubation at 34.5 °C for 155 min. The formononetin content fluctuated between 0.74 and 1.96 mg/g of fresh weight, where Precoz-3, Precoz-1, and Superqueli-INIA presented the highest production.

State-specific gating of salient cues by midbrain dopaminergic input to basal amygdala.

Basal amygdala (BA) neurons guide associative learning via acquisition of responses to stimuli that predict salient appetitive or aversive outcomes. We examined the learning- and state-dependent dynamics of BA neurons and ventral tegmental area (VTA) dopamine (DA) axons that innervate BA (VTADA→BA) using two-photon imaging and photometry in behaving mice. BA neurons did not respond to arbitrary visual stimuli, but acquired responses to stimuli that predicted either rewards or punishments. Most VTADA→BA axons were activated by both rewards and punishments, and they acquired responses to cues predicting these outcomes during learning. Responses to cues predicting food rewards in VTADA→BA axons and BA neurons in hungry mice were strongly attenuated following satiation, while responses to cues predicting unavoidable punishments persisted or increased. Therefore, VTADA→BA axons may provide a reinforcement signal of motivational salience that invigorates adaptive behaviors by promoting learned responses to appetitive or aversive cues in distinct, intermingled sets of BA excitatory neurons.

Analysis of Ag(I) Biocide in Water Samples Using Anodic Stripping Voltammetry with a Boron-Doped Diamond Disk Electrode.

The electroanalytical performance of a new commercial boron-doped diamond disk and a traditional nanocrystalline thin-film electrode were compared for the anodic stripping voltammetric determination of Ag(I). The diamond disk electrode is more flexible than the planar film as the former is compatible with most electrochemical cell designs including those incorporating magnetic stirring. Additionally, mechanical polishing and surface cleaning are simpler to execute. Differential pulse anodic stripping voltammetry (DPASV) was used to detect Ag(I) in standard solutions after optimization of the deposition potential, deposition time and scan rate. The optimized conditions were used to determine the concentration of Ag(I) in a NASA simulated potable water sample and a NIST standard reference solution. The electrochemical results were validated by ICP-OES measurements of the same solutions. The detection figures of merit for the disk electrode were as good or superior to those for the thin-film electrode. Detection limits were ≤5 µg L-1 (S/N = 3) for a 120 s deposition period, and response variabilities were <5% RSD. The polished disk electrode presented a more limited linear dynamic range presumably because of the reduced surface area available for metal phase formation. The concentrations of Ag(I) in the two water samples, as determined by DPASV, were in good agreement with the concentrations determined by ICP-OES.

Isatin Detection Using a Boron-Doped Diamond 3-in-1 Sensing Platform.

Boron-doped diamond (BDD) is a promising electrochemical tool that exhibits excellent chemical sensitivity and stability. These intrinsic advantages coupled with the material's vast microfabrication flexibility make BDD an attractive sensing device. In this study, two different 3-in-1 BDD electrode sensors were fabricated, characterized, and investigated for their capability to detect isatin, an anxiogenic indole that possesses anticonvulsant activity. Each device was comprised of a working, reference, and auxiliary electrode, all made of BDD. Two different working electrode geometries were studied, a 2 mm diameter macroelectrode (MAC) and a microelectrode array (MEA). The BDD quasi-reference electrode was studied by measuring its potential against a traditional Ag/AgCl reference electrode. While the potential shifted as a function of solution pH, a miniscule potential drift was observed when holding the solution pH constant. Specifically, the BDD quasi-reference electrode had a potential of -0.2 V (vs Ag/AgCl) in a pH 7 solution, and this remained stable for a 30-h time period. For the detection of isatin, solutions were analyzed using both sensors in pH 7.4 phosphate buffered saline (PBS). Using the MEA sensor, the limit of detection (LOD, (3σ)/m) for isatin was found to be 0.04 µM; an increase to 0.22 µM was observed with the MAC sensor. These results were compared to those obtained from UV-vis spectrophotometry, where a 0.57 µM LOD was observed. The feasibility for use in a complex sample matrix was also examined by completing measurements in urine simulant. The results presented herein indicate that both 3-in-1 BDD sensors are applicable at low limits of detection with potential application as an electrochemical detector for chromatographic methods.

Conocimientos de las usuarias sobre prevención de cáncer de cérvix en el Centro de Salud El Éxito Vitarte - 2013 / Knowledge of the women users about the prevention of cervical cancer in the Health Center El Exito, Vitarte - 2013

El objetivo: Determinar los conocimientos de las usuarias sobre prevención del Cáncer de cérvix en el Centro de Salud "El Éxito"-Vitarte 2013. Material y método: El estudio es de nivel aplicativo, tipo cuantitativo, método descriptivo de corte transversal. Y la población estuvo conformado por 30 usuarias. La técnica utilizada es la entrevista y el instrumento un cuestionario, aplicado previo consentimiento informado. Resultados: El conocimiento general en la prevención del cáncer de cérvix; el 77 por ciento (23) no conocen y 23 por ciento (7) conoce sobre medidas de prevención, y en la dimensión de la prevención primaria; 73 por ciento (22) no conoce y 27 por ciento (8) conoce, y/o en la dimensión de la prevención secundaria 50 por ciento (15) no conoce y 50 por ciento (15) conoce: Conclusiones: Las usuarias que acuden al Centro de Salud "El Éxito", no conocen sobre la prevención del Cáncer de Cérvix, y en la prevención primaria no tienen conocimiento sobre los factores de riesgos. Sin embargo en la prevención secundaria las usuarias conocen y no conocen al realizar un diagnóstico precoz y tratamiento oportuno.

Purpose: To determine the knowledge of patients about prevention of cervical cancer in the Health Centre "El Exitoõ - Vitarte 2013. Material and approach: The study is made on the application level, of the quantitative type, a descriptive approach of the cross section. The population consisted of 30 users. The used technique were interviews and the instrument a questionnaire applied with prior informed consent. Results: The general knowledge in the prevention of cervical cancer about prevention methods is not known by 77 per cent (23) and known by 23 per cent (7). The dimension of primary prevention is not known by 73 per cent (22) and known by 27 per cent (8), and/or the dimension of secondary prevention is not known by 50 per cent (15) and known by 50 per cent (15). Conclusions: The patients who come to the Health Center "El Exito" do not know about cervical cancer prevention, they are not aware of the risk factors in the primary prevention. However in secondary prevention patients do know and do not know when an early diagnosis and treatment is made.

Synergistic activity of fenretinide and the Bcl-2 family protein inhibitor ABT-737 against human neuroblastoma.

PURPOSE: Fenretinide (4-HPR) is a cytotoxic retinoid with minimal systemic toxicity that has shown clinical activity against recurrent high-risk neuroblastoma. To identify possible synergistic drug combinations for future clinical trials, we determined whether ABT-737, a small-molecule BH3-mimetic that inhibits most proteins of the antiapoptotic Bcl-2 family, could enhance 4-HPR activity in neuroblastoma. EXPERIMENTAL DESIGN: Eleven neuroblastoma cell lines were tested for the cytotoxic activity of 4-HPR and ABT-737 as single agents and in combination using the DIMSCAN fluorescence digital imaging cytotoxicity assay. The effect of these agents alone and in combination on mitochondrial membrane depolarization and apoptosis (by flow cytometry), cytochrome c release, caspases, Bax-α, t-Bid, and Bak activation, and subcutaneous xenografts in nu/nu mice was also determined. RESULTS: Multilog synergistic cytotoxicity was observed for the drug combination in all of the 11 neuroblastoma cell lines tested, including MDR lines and those insensitive to either drug as single agents. 4-HPR + ABT-737 induced greater mitochondrial membrane depolarization and mitochondrial cytochrome c release, greater activation of caspases, Bax-α, t-Bid, and Bak, and a higher level of apoptosis than either drug alone. In vivo, 4-HPR + ABT-737 increased the event-free survival of the MDR human neuroblastoma line CHLA-119 implanted subcutaneously in nu/nu mice (194.5 days for the combination vs. 68 days for ABT-737 and 99 days for 4-HPR). CONCLUSION: Thus, the combination of 4-HPR with a BH3-mimetic drug warrants clinical trials in recurrent neuroblastoma.

Características clínicas da osteogênese imperfeita do tipo I e da dentinogênese imperfeita / Clinical features of type I osteogenesis imperfecta and dentinogenesis imperfecta

Objetivos: Realizar uma revisão da literatura sobre as características da osteogênese imperfeita Tipo I, enfatizando uma doença comumenteassociada à mesma, a dentinogênese imperfeita, a fim de alertar os profissionais da saúde sobre as significativas alterações dentais que atingem os indivíduos com osteogênese imperfeita. Fontes Pesquisadas: Artigos científicos em diferentes bases de dados. Síntese dos dados: A osteogêneseimperfeita é uma alteração óssea de origem genética que envolve a síntese de colágeno. A síntese deficiente de colágeno leva ao aparecimento de ossos enfraquecidos e quebradiços, sendo outros sinais que acompanham esta doença o tom azulado da esclerótica e a perda de audição. A manifestação dental mais importante é a dentinogênese imperfeita, uma doença genética que afeta o desenvolvimento dentário, provocando a descoloração azul acinzentado ou marrom amarelado e excessiva translucidez. Os dentes são enfraquecidos e sofrem desgaste rapidamente. Conclusão: A osteogêneseimperfeita pode apresentar alterações graves da estrutura dentinária. Esta disfunção afeta a função e a estética em quase toda a dentição, ocasionandograndes transtornos aos indivíduos acometidos. Os tratamentos odontológicos serão mais promissoresquanto mais cedo forem efetuados, devendo ocorrer a interação médico-cirurgião-dentista precocemente, para a promoção de saúde e redução de danos.

Objectives: To perform a brief literaturereview about the clinical characteristics of osteogenesis imperfecta Type I with emphasis in a common oral finding known as dentinogenesis imperfecta. The overall goal is to inform health care professionals that oral changes are present in patients with osteogenesisimperfecta. Researched sources: Free choice of pertinent literature articles related to osteogenesis and dentinogenesis imperfecta. Data synthesis: Osteogenesis imperfecta is an osseous disease caused by deficientcollagen synthesis due to genetic disorders. The impaired collagen synthesis leads to the development ofweak bones which are easily broken. Common findings in this disease include blue sclera and deafness due toosteosclerosis. The most common oral alteration caused by osteogenesis imperfecta is dentinogenesis imperfecta,also a genetic disorder which impairs dental formation and causes teeth translucence and discoloration(grayish blue to yellowish brown). Teeth become weak, non resistant to attrition and are therefore easilybroken. Conclusion: Osteogenesis imperfecta can present severe dental changes which results in loss of tooth function and esthetics and therefore can have an impact in the overall live of an individual. Dental treatment will be more successful if there were institutedearly in a multidisciplinary approach.

Improved oral delivery of N-(4-hydroxyphenyl)retinamide with a novel LYM-X-SORB organized lipid complex.

PURPOSE: Fenretinide [N-(4-hydroxyphenyl)retinamide (4-HPR)] is a cytotoxic retinoid that suffers from a wide interpatient variation in bioavailability when delivered orally in a corn oil capsule. The poor bioavailability of the capsule formulation may have limited responses in clinical trials, and the large capsules are not suitable for young children. To support the hypothesis that a novel organized lipid matrix, LYM-X-SORB, can increase the oral bioavailability of fenretinide, fenretinide in LYM-X-SORB matrix and in a powderized LYM-X-SORB formulation was delivered to mice. EXPERIMENTAL DESIGN: Fenretinide was delivered orally to mice as the contents of the corn oil capsule, in LYM-X-SORB matrix (4-HPR/LYM-X-SORB matrix) or in a LYM-X-SORB matrix powderized with sugar and flour (4-HPR/LYM-X-SORB oral powder). Levels of 4-HPR, and its principal metabolite, N-(4-methoxyphenyl)retinamide, were assayed in plasma and tissues. RESULTS: In a dose-responsive manner, from 120 to 360 mg/kg/d, delivery to mice of 4-HPR in LYM-X-SORB matrix, or as 4-HPR/LYM-X-SORB oral powder, increased 4-HPR plasma levels up to 4-fold (P<0.01) and increased tissue levels up to 7-fold (P<0.01) compared with similar doses of 4-HPR delivered using capsule contents. Metabolite [N-(4-methoxyphenyl)retinamide] levels mirrored 4-HPR levels. Two human neuroblastoma murine xenograft models showed increased survival (P<0.03), when treated with 4-HPR/LYM-X-SORB oral powder, confirming the bioactivity of the formulation. CONCLUSIONS: 4-HPR/LYM-X-SORB oral powder is a novel, oral drug delivery formulation, suitable for pediatric use, which warrants further development for the delivery of fenretinide in the treatment of cancer. A phase I clinical trial in pediatric neuroblastoma is in progress.

Educação inclusiva: formação de cidadãos para uma vida plena / Inclusive education: citizens' formation for a richen life

Tudo o que é relativo ao social está sendo redescoberto na contemporaneidade, levantando questões que não haviam sido abordadas efetivamente e acentuando posicionamentos comprometidos com valores voltados para o bem comum. Rediscute-se o compromisso social, e discute-se essencialmente o que vem a ser esse socius, ainda capaz de excluir. Dentre os excluídos temos os portadores de deficiência, categorizados a partir do déficit e representados pela falta, situando-se à margem de toda e qualquer participação na comunidade. A Educação Inclusiva surge dentro do contexto de reformulação dos parâmetros do ensino médio e fundamental, que prevê profundas alterações no pensar a própria educação, num processo de singularização que se estabelece na valorização da diferença e na estimulação das diversas formas de se atuar e participar ativamente no social, fazendo com que portadores de deficiência possam incidir no mundo, contribuindo para seu desenvolvimento, na busca pela autonomia. (AU)

Everything that is relative to the social is being rediscovered in the contemporaneity, raising questions that had not been deeply approached and accentuating committed positions with values focused on the commonwealth. Social commitment is being discussed, and mainly what is the meaning of this socius which is still able to exclude. Among the excluded we have handicapped bearers, classified from deficit and represented by the lack, locating themselves to the margin of all and any participation in the community. The Inclusive Education appears inside the context of reformulation of the medium and fundamental educational system guidelines that foresees deep alterations in thinking Education itself, in a singularization process that settles down in the valorization of the difference and in the stimulation in the several ways of acting and participating actively in the social, allowing handicapped bearers to happen in the world, contributing to their development in the search for the autonomy. (AU)