Synthesis of Symmetrical and Nonsymmetrical Polyenes by Iterative and Bidirectional Palladium-Catalyzed Cross-Coupling Reactions.

Bifunctional unsaturated reagents designed to undergo palladium-catalyzed cross-coupling reactions with complementary polyenyl connective fragments are highly useful for the undoubtedly challenging synthesis of polyenes. The current toolkit of building blocks for the bidirectional formation of Csp2 -Csp2 single bonds of polyenes includes homo-bisfunctionalized reagents with equal or unequal reactivity (due to steric and/or electronic factors), and hetero-bisfunctionalized counterparts containing either two different nucleophiles, two electrophiles or one of these functionalities and a latent nucleophile that can be unmasked when desired. The combination of these bifunctional linchpin reagents using tactics that modulate the reactivity of each terminus in order to achieve the required connection have streamlined the synthesis of polyenes of great complexity using (iterative) cross-coupling methods for Csp2 -Csp2 bond formation. Reaction conditions for the Pd-catalyzed cross-coupling reactions are mild and functional-group-tolerant, and therefore these protocols allow to construct the polyene structures using shorter unsaturated reactants with the desired geometries, since in general the products preserve the stereochemical information of the connected cross-coupling partners.

The use of lymphocyte-depleting antibodies in specific populations of kidney transplant recipients: A systematic review and meta-analysis.

BACKGROUND: Recommendations of the use of antibody induction treatments in kidney transplant recipients (KTR) are based on moderate quality and historical studies. This systematic review aims to reevaluate, based on actual studies, the effects of different antibody preparations when used in specific KTR subgroups. METHODS: We searched MEDLINE and CENTRAL and selected randomized controlled trials (RCT) and observational studies looking at different antibody preparations used as induction in KTR. Comparisons were categorized into different KTR subgroups: standard, high risk of rejection, high risk of delayed graft function (DGF), living donor, and elderly KTR. Two authors independently assessed the risk of bias. RESULTS: Thirty-seven RCT and 99 observational studies were finally included. Compared to anti-interleukin-2-receptor antibodies (IL2RA), anti-thymocyte globulin (ATG) reduced the risk of acute rejection at two years in standard KTR (RR 0.74, 95%CI 0.61-0.89) and high risk of rejection KTR (RR 0.55, 95%CI 0.43-0.72), but without decreasing the risk of graft loss. We did not find significant differences comparing ATG vs. alemtuzumab or different ATG dosages in any KTR group. CONCLUSIONS: Despite many studies carried out on induction treatment in KTR, their heterogeneity and short follow-up preclude definitive conclusions to determine the optimal induction therapy. Compared with IL2RA, ATG reduced rejection in standard-risk, highly sensitized, and living donor graft recipients, but not in high DGF risk or elderly recipients. More studies are needed to demonstrate beneficial effects in other KTR subgroups and overall patient and graft survival.

An integrative water quality evaluation in two surface water bodies from a tropical agricultural region in Cartago, Costa Rica.

A monitoring study was carried out in two micro-catchments in the Reventazón basin, in Northern Cartago, Costa Rica; pesticide occurrence and water quality were analyzed. Twelve pesticides were detected, five insecticides (chlorpyrifos, carbofuran, cypermethrin, imidacloprid, and oxamyl), four fungicides (carbendazim, imazalil, metalaxyl, and thiabendazole), and three herbicides (diuron, linuron, and terbutryn); eight of them presented risk quotients RQ >1, which implies a high risk for the environment. The water quality evaluation included fourteen physicochemical and microbiological parameters, out of which thermotolerant coliforms, nitrate, and total phosphorus exceeded a selected threshold value in every sample. Five metals were also included in the evaluation, Pb was the most frequent, followed by few detections of Cd, Cu, and Cr. Four water quality indexes (WQIs) were applied, two of them, the CCME WQI, based on physicochemical parameters, and the BMWP-CR WQI, based on benthic macroinvertebrate recount adapted to Costa Rican species, categorized all the sampling points as "bad" and "very bad" quality. This work of monitoring is important in the Latin American region, where there is a lack of information for regulation improvement and management decisions. These results showed poor management of the micro-catchments in this agricultural rural area.

Total synthesis of nahuoic acid A via a putative biogenetic intramolecular Diels-Alder (IMDA) reaction.

Inspired by the biogenetic proposal of an intramolecular Diels-Alder (IMDA) cycloaddition, the total synthesis of natural product nahuoic acid A, a cofactor-competitive inhibitor of the epigenetic enzyme lysine methyl transferase SETD8, has been carried out. A non-conjugated pentaenal precursor was synthesized with high levels of stereoselectivity at seven stereogenic centers and with the appropriate control of double bond geometries. Although the IMDA reaction of the non-conjugated pentaenal using Me2AlCl for catalysis at -40 °C selectively afforded the trans-fused diastereomer corresponding to the Re-endo mode of cycloaddition, under thermal reaction conditions it gave rise to a mixture of diastereomers, that preferentially formed through the exo mode, including the cis-fused angularly-methylated octahydronaphthalene diastereomer precursor of nahuoic acid A. The natural product could be obtained upon oxidation and overall deprotection of the hydroxyl groups present in the Si-exo IMDA diastereomer.

Pesticide occurrence and water quality assessment from an agriculturally influenced Latin-American tropical region.

A monitoring study was carried out in three agriculturally influenced microcatchments in Costa Rica during 2012-2014, for pesticides and water quality parameters. A total of 42 pesticides were analyzed, detecting the following in water samples: two herbicides (oxyfluorfen, diuron), four insecticides (carbofuran, chlorpyrifos, oxamyl, ethion), and two fungicides (thiabendazole, carbendazim); while in sediment samples only the insecticides, chlorpyrifos and cypermethrin were found. Water quality was also assessed by the Canadian Council of Ministers of the Environment Water Quality Index and the National Sanitation Water Quality Index, the first one classified most of the sampling point as marginal and poor quality while the second one classified most of them as good quality, the most affected parameters were nitrate, phosphorous, suspended solids and organic matter content. The results suggest that the water quality in the microcatchments seems to be affected by the nearby agricultural and urban activities in the region.

Pesticide monitoring and ecotoxicological risk assessment in surface water bodies and sediments of a tropical agro-ecosystem.

A pesticide monitoring study including 80 and 60 active ingredients (in surface waters and sediments, respectively) was carried out in a river basin in Costa Rica during 2007-2012. A special emphasis was given on the exceptional ecological conditions of the tropical agro-ecosystem and the pesticide application strategies in order to establish a reliable monitoring network. A total of 135 water samples and 129 sediment samples were collected and analyzed. Long-term aquatic ecotoxicological risk assessment based on risk quotient in three trophic levels was conducted. Short-term risk assessment was used to calculate the toxic unit and prioritization of sampling sites was conducted by the sum of toxic units in both aquatic and sediment compartments. Dimethoate (61.2 µg/L), propanil (30.6 µg/L), diuron (22.8 µg/L) and terbutryn (4.8 µg/L) were detected at the highest concentrations in water samples. Carbendazim and endosulfan were the most frequently detected pesticides in water and sediment samples, respectively. Triazophos (491 µg/kg), cypermethrin (71.5 µg/kg), permethrin (47.8 µg/kg), terbutryn (38.7 µg/kg), chlorpyrifos (18.2 µg/kg) and diuron (11.75 µg/kg) were detected at the highest concentrations in sediment samples. The pesticides carbendazim, diuron, endosulfan, epoxyconazole, propanil, triazophos and terbutryn showed non-acceptable risk even when a conservative scenario was considered. Sum TUsite higher than 1 was found for one and two sampling sites in water and sediment compartments, respectively, suggesting high acute toxicity for the ecosystem. MAIN FINDING OF THE WORK: Exceptional ecological conditions of the tropical agro-ecosystem affect the fate of pesticides in water and sediment environment differently than the temperate one.

Variables associated with family breakdown in healthy and obese/overweigh adolescents.

OBJECTIVE: To evaluate the presence of family breakdown factors among eutrophic and overweight/obese adolescents. METHODS: Cross-sectional study of 242 students aged between 14 and 19 years old, from a public school. Each student was weighed, measured and answered a questionnaire with closed questions addressing the presence of family breakdown factors. The adolescents were divided in two groups: euthophic and overweight/obese. The answers of both groups were compared by Fisher's exact and Mann-Whitney tests. RESULTS: There was no statistically significant difference in the prevalence of the studied factors between the two groups. Comparing the number of positive answers (presence of family breakdown factors) and negative ones (absence of family breakdown factors), no difference was observed between the groups. CONCLUSIONS: The inclusion of a control group showed that factors of family breakdown, usually identified as associated with obesity in adolescents, may also be present in eutrophic adolescents.

Variables associated with family breakdown in healthy and obese/ overweigh adolescents / Investigacion de factores de desagregacion familiar en adolescentes eutroficos y adolescentes con sobrepeso/obesidad / Fatores de desagregacao familiar em adolescentes eutroficos e nos portadores de sobrepeso/obesidade

Objective: To evaluate the presence of family breakdown factors among eutrophic and overweight/obese adolescents. Methods: Cross-sectional study of 242 students aged between 14 and 19 years old, from a public school. Each student was weighed, measured and answered a questionnaire with closed questions addressing the presence of family breakdown factors. The adolescents were divided in two groups: euthophic and overweight/obese. The answers of both groups were compared by Fisher's exact and Mann-Whitney tests. Results: There was no statistically significant difference in the prevalence of the studied factors between the two groups. Comparing the number of positive answers (presence of family breakdown factors) and negative ones (absence of family breakdown factors), no difference was observed between the groups. Conclusions: The inclusion of a control group showed that factors of family breakdown, usually identified as associated with obesity in adolescents, may also be present in eutrophic adolescents. .

Objetivo: Investigar la existencia de factores de desagregación familiar entre adolescentes eutróficos y portadores de sobrepeso/obesidad. Métodos: Estudio transversal, implicando a 242 alumnos de una escuela pública, de 14 a 19 años, que fueron pesados, medidos y contestaron a un cuestionario con cuestiones cerradas, el que investigó la presencia de factores de desagregación familiar. Enseguida, los adolescentes fueron divididos en dos grupos, eutróficos y portadores de sobrepeso/obesidad, y las respuestas fueron confrontadas y analizadas mediante las pruebas exacto de Fisher y de Mann-Whitney. Resultados: No hubo diferencia significante para la prevalencia de los factores estudiados entre los dos grupos cuando vistos en separado e incluso cuando las variables fueron analizadas en conjunto. Comparándose el número de respuestas positivas (presencia del factor de desagregación familiar) y negativas (ausencia del factor de desagregación familiar), no se observó diferencia entre los dos grupos. Conclusiones: El análisis con la inclusión de un grupo control mostró que factores relacionados a la desagregación familiar, habitualmente señalados como asociados a la obesidad en adolescentes, pueden estar presentes también en adolescentes eutróficos. .

Objetivo: Investigar a existência de fatores de desagregação familiar em adolescentes eutróficos e nos portadores de sobrepeso/obesidade. Métodos: Estudo transversal de 242 alunos de uma escola pública, de 14 a 19 anos, que foram pesados, medidos e responderam a um questionário com questões fechadas, o qual investigou a presença de fatores de desagregação familiar. Em seguida, os adolescentes foram divididos em dois grupos, eutróficos e portadores de sobrepeso/obesidade, e as respostas foram confrontadas e analisadas por meio dos testes exato de Fisher e de Mann-Whitney. Resultados: Não houve diferença significante para a prevalência dos fatores estudados entre os dois grupos. Comparando-se o número de respostas positivas (presença do fator de desagregação familiar) e negativas (ausência do fator de desagregação familiar), não se observou diferença entre os dois grupos. Conclusões: A análise com a inclusão de um grupo controle mostrou que fatores ligados à desagregação familiar, habitualmente apontados como associados à obesidade em adolescentes, podem estar presentes também em adolescentes eutróficos. .

Uso del Pesticide Impact Rating Index(PIRI) para estimar la peligrosidad del uso deplaguicidas en el cultivo de cebolla (Allium cepa L. ) / Use of Pesticide Impact Rating Index (PIRI) for evaluating dangers ofpesticide use in onion (Allium cepa L. ) culture / Uso de “Pesticide Impact Rating Index” (PIRI) para estimar apericulosidade do uso de pesticidas no cultivo da cebola A( llium cepa L. )

Se utilizó el programa Pesticide Impact Rating Index (PIRI) para estimar la peligrosidad del uso de 30 plaguicidas en elcultivo de cebolla (Allium cepa L.) para la calidad del agua de la quebrada Sanatorio, ubicada en la comunidad de TierraBlanca, en el cantón de Cartago, Costa Rica. La información se obtuvo del Servicio Fitosanitario del Estado y de encuestasaplicadas a los productores de la zona de Tierra Blanca. Los resultados obtenidos con el PIRI se contrastaron con los nivelesde residuos de plaguicidas en sedimentos y agua encontrados en la quebrada en el monitoreo realizado durante losmeses de abril, junio, agosto y octubre del 2011. Aproximadamente el 50% de los plaguicidas autorizados se clasificaroncomo extremadamente tóxicos, y cerca del 40% se clasificaron como muy móviles. Por otro lado, de los plaguicidas noregistrados, el 60% fue catalogado como extremadamente tóxicos, y el 40% como muy móviles. El agua de la quebrada esutilizada para riego de los cultivos de fincas aledañas al cauce, por lo que esta situación podría representar un problemasobre la salud pública.

Usou-se o programa Pesticide Impact Rating Index (PIRI) para estimar o risco do uso de 30 inseticidas no cultivo dacebola (Allium cepa L.) para a qualidade da água de quebrada Sanatorio, localizado na comunidade de Terra Branca, nocantão de Cartago, Costa Rica. Obtiveram-se informações do Serviço Fitossanitário do Estado e de pesquisas feitas juntoaos produtores da área de Terra Branca. Os resultados obtidos com o PIRI confirmaram os níveis de resíduos de inseticidaem sedimento e água encontrada na quebrada em uma monitoração realizada durante abril, junho, agosto e outubro de2011. Aproximadamente 50% dos inseticidas autorizados mostraram-se extremamente venenosos, e perto de 40% comomuito móveis. Por outro lado, dos inseticidas não registrados, 60% catalogaram-se como extremamente venenosos, e40%, como muito móveis. A água quebrada é usada para a irrigação do cultivo de fazendas próximas do leito do rio,situação que pode gerar problemas de saúde pública.

Using the program Pesticide Impact Rating Index (PIRI) to estimate the risk of the use of 30 insecticides in the cultivationof onion (Allium cepa L.) for water quality from quebrada Sanatorio, located in the community of Tierra Blanca,in the canton of Carthage, Costa Rica. Information was obtained from the Phytosanitary Service of the State (ServicioFitosanitario del Estado) and from surveys applied to the producers of the area of Tierra. The results obtained with PIRIwere confirmed at the levels of residues of insecticides in sediments and water found in the gorge in a monitoringrealized during April, June, August and October, 2011. Approximately 50% of the authorized insecticides qualifiedas extremely poisonous, and close to 40% qualified as very mobile. On the other hand, from the non registered insecticides,60% were catalogued as extremely poisonous, and 40% as very mobile. The water of the gorge is used forirrigation of the cultivation of bordering farms to the river bed, and for that reason this situation can generate problemson public health.

Caracterización de la calidad del agua de la quebrada sanatorio en Tierra Blanca ubicada en una zona agrícola de la provincia de Cartago y sus implicaciones para la salud pública / Quality of water from quebrada sanatorio (Tierra Blanca), in the county region of Cartago province and impacts on public health / Qualidade de água de quebrada sanatorio (Tierra Blanca), na região agrícola da província de Cartago, e seus impactos sobre a saúde pública

Se monitoreó la calidad del agua de la Quebrada Sanatorio (Tierra Blanca, Cartago, Costa Rica), durante abril, junio, agosto y octubre de 2011. Se establecieron tres puntos de muestreo utilizando una metodología de estratificación. Se realizó un análisis biofísico de la zona de estudio, así como la caracterización fisicoquímica y microbiológica del cuerpo de agua, determinación de residuos de plaguicidas en agua y sedimentos y aplicación de índice BMWP adaptado a Costa Rica. Se determinó una elevada contaminación en la quebrada por coliformes fecales y E. coli, nutrientes y plaguicidas, quefueron detectados en agua y sedimentos, demás se determinó una deficiente calidad del recurso hídrico según el índice BMWP-CR. Se concluye que el agua no es adecuada para riego y pone en riesgo la salud de los agricultores, sus familias y consumidores, así como se ve afectada la seguridad alimentaria.

This project was monitoring water quality of the stream “Quebrada Sanatorio” (Tierra Blanca, Cartago, Costa Rica), during April, June, August and October 2011. It established three sampling points using a stratification methodology. It was performed biophysical analysis of the area of study. It was determined physicochemical and microbiological characteristics of thewater body, determination of pesticide residues in water and sediments and application BMWP index adapted to Costa Rica.It was established high contamination in the stream for faecal coliforms and E. coli, also nutrients and pesticides in water and sediments. It was also determined poor quality of water resources by the index BMWP-CR. It is concluded that the water is not suitable for irrigation and it had a risks the health of farmers, their families and consumers, as well as food security is affected.

Estudo do efeito da depleção serotonérgica sobre a inibição latente medida em paradigmas sensíveis a baixas doses de anfetamina

A inibição latente (IL) refere-se ao retardo na aquisição do controle do comportamento por um estímulo que foi, inicialmente, apresentado desacompanhado de reforço, e que, em seguida, será utilizado como estímulo condicionado. Este fenômeno tem se mostrado promissor para acessar anormalidades observadas em pacientes esquizofrênicos, e como tal, é grande o interesse no estudo de seu substrate neural. Numerosos trabalhos indicam que a integridade do sistema dopaminérgico mesolímbico é essencial para o desenvolvimento da inibição latente. A participação de outros sistemas neurotransmissores tem sido menos explorada. Para estudar o papel da serotonina (5-HT) na IL foi verificado o efeito da depleção serotonérgica sobre a IL deratos medida em dois paradigmas de condicionamento sensíveis ao efeito de baixas doses de anfetamina, a esquiva passiva e o condicionamento aversivo ao saber. O procedimento a os parâmetros adotados para verificação da IL na esquiva passiva foram obtidos após uma série de experimentos de calibração. Na esquiva passiva, os ratos eram confinados no compartimento escuro de uma caixa de esquiva per 5 min a recebiam dois choques (1,2 mA, 5 s). Para a verificação da IL, um grupo de ratos(pré-expostos) era previamente colocado no compartimento escuro em três sessões diárias. A IL foi observada pela diminuição da latência de esquiva de ratos pré-expostos quando comparados à latência de esquiva de ratos não pré-expostos. No condicionamento aversivo ao saber, os ratos deveriam aprender a associação entre a ingestão de glicose e o mal-estar induzido pela administração intraperitonial de 64 mg/kg de LiCI. O grupo de ratos pré-expostos teve acesso à ingestão de glicose durante 1:15 min per três sessões diárias, antes do condicionamento. Após o estabelecimento da associação entre ingestão de glicose a mal-estar, os ratos pré-expostos e não pré-expostos tiveram acesso a dois tubos de água, um contendo água e outro, glicose. A IL foi expressada pelo aumento da preferência per glicose observada em ratos pré-expostos a quando comparado ao grupo de ratos não pré-expostos. Em ambos paradigmas, a administração intraperitonial de 0,25mg/kg a 0,5 mg/kg de d-anfetamina injetadas diariamente nos três dias de pré-exposição e no dia do condicionamento prejudicaram a IL...(AU)