Genome-wide association study of virologic response with efavirenz-containing or abacavir-containing regimens in AIDS clinical trials group protocols.

BACKGROUND: Efavirenz and abacavir are components of recommended first-line regimens for HIV-1 infection. We used genome-wide genotyping and clinical data to explore genetic associations with virologic failure among patients randomized to efavirenz-containing or abacavir-containing regimens in AIDS Clinical Trials Group (ACTG) protocols. PARTICIPANTS AND METHODS: Virologic response and genome-wide genotype data were available from treatment-naive patients randomized to efavirenz-containing (n=1596) or abacavir-containing (n=786) regimens in ACTG protocols 384, A5142, A5095, and A5202. RESULTS: Meta-analysis of association results across race/ethnic groups showed no genome-wide significant associations (P<5×10) with virologic response for either efavirenz or abacavir. Our sample size provided 80% power to detect a genotype relative risk of 1.8 for efavirenz and 2.4 for abacavir. Analyses focused on CYP2B genotypes that define the lowest plasma efavirenz exposure stratum did not show associations nor did analysis limited to gene sets predicted to be relevant to efavirenz and abacavir disposition. CONCLUSION: No single polymorphism is associated strongly with virologic failure with efavirenz-containing or abacavir-containing regimens. Analyses to better consider context, and that minimize confounding by nongenetic factors, may show associations not apparent here.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Modulation of genetic associations with serum urate levels by body-mass-index in humans.

We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 x 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10-8), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10-8), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10-4). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.

TBS reflects trabecular microarchitecture in premenopausal women and men with idiopathic osteoporosis and low-traumatic fractures.

Transiliac bone biopsies, while widely considered to be the standard for the analysis of bone microstructure, are typically restricted to specialized centers. The benefit of Trabecular Bone Score (TBS) in addition to areal bone mineral density (aBMD) for fracture risk assessment has been documented in cross-sectional and prospective studies. The aim of this study was to test if TBS may be useful as a surrogate to histomorphometric trabecular parameters of transiliac bone biopsies. Transiliac bone biopsies from 80 female patients (median age 39.9years-interquartile range, IQR 34.7; 44.3) and 43 male patients (median age 42.7years-IQR 38.9; 49.0) with idiopathic osteoporosis and low traumatic fractures were included. Micro-computed tomography values of bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), structural model index (SMI) as well as serum bone turnover markers (BTMs) sclerostin, intact N-terminal type 1 procollagen propeptide (P1NP) and cross-linked C-telopeptide (CTX) were investigated. TBS values were higher in females (1.282 vs 1.169, p< 0.0001) with no differences in spine aBMD, whereas sclerostin levels (45.5 vs 33.4pmol/L) and aBMD values at the total hip (0.989 vs 0.971g/cm(2), p<0.001 for all) were higher in males. Multiple regression models including: gender, aBMD and BTMs revealed TBS as an independent, discriminative variable with adjusted multiple R(2) values of 69.1% for SMI, 79.5% for Tb.N, 68.4% for Tb.Sp, and 83.3% for BV/TV. In univariate regression models, BTMs showed statistically significant results, whereas in the multiple models only P1NP and CTX were significant for Tb.N. TBS is a practical, non-invasive, surrogate technique for the assessment of cancellous bone microarchitecture and should be implemented as an additional tool for the determination of trabecular bone properties.

Degradación de T-patterns en estudios observacionales: Un estudio sobre la eficacia en el ataque de fútbol sala

Una de las técnicas analíticas más novedosas en el ámbito de la metodología observacional es la que permite la detección de T-patterns (estructuras regulares de conducta) mediante el software THEME, que analiza datos observacionales en búsqueda de relaciones de intervalo crítico en sentido ascendente (desde T-pattern simples, dos eventos que se relacionan en un primer nivel, a T-patterns complejos constituidos por diferentes eventos relacionados en distintos niveles). En el presente artículo se analiza esta cuestión, la degradación de los T-patterns, que hasta el momento ha sido puntualmente estudiada. Para ello, se utiliza el muestreo observacional constituido por el conjunto de las secuencias que acaban en gol (n= 23) protagonizadas por el F.C. Barcelona durante el Play Off Final de la liga española 2012-13 de fútbol sala. De esta forma este trabajo satisface un segundo objetivo, en este caso disciplinar, de analizar la e'cacia en la construcción de la fase ofensiva en el fútbol sala; habiéndose tipi'cado que las secuencias que 'nalizan en gol se caracterizan por conseguir, mediante juego combinativo, un lanzamiento desde sector de'nición-corredor central.

Determinação espectrofotométrica de cefalexina em formulações farmacêuticas explorando a sua reação de transferência de carga com a quinalizarina

This work proposes a new simple and fast spectrophotometric method for cephalexin determination in pharmaceutical formulations. The method is based on the charge transfer reaction between cephalexin and quinalizarin in dimethylsulfoxide medium. Several analytical parameters related to the system were optimized and the reaction was characterized in terms of stoichiometry. Also, association constant and apparent molar absorptivity of the product were determined. The method presented a limit of detection of 0.46 mg L-1 and a quantification limit of 1.5 mg L-1. It was successfully applied in the determination of cephalexin in two samples of commercial pharmaceutical formulations.

Avaliação do método das adições de analito para a determinação de sódio em álcool combustível por espestrometria de emissão atômica em chama

O método empregado para a determinação de sódio por espectrometria de emissão atômica em chama, foi o das adições de analito sendo as intensidades de emissão representadas em função das concentrações de analito adicionadas às várias porções da amostra, numa faixa linear de 0 - 0,300 mg Na L-1, empregando-se 2,1 g K L-1 como supressor de ionização. Foram analisadas 20 amostras comerciais de álcool etílico hidratado combustível (AEHC), coletadas em diferentes postos de abastecimento, na cidade de Araraquara e os resultados obtidos encontram-se no intervalo, desde menor que o limite de detecção (0,0072 mg Na L-1) até 1,55 mg Na L-1. Os limites de detecção referentes à determinação de sódio em cada amostra situam-se entre 0,0026 e 0,0239 mg Na L-1. A porcentagem de recuperação variou no intervalo de 95 a 104 %. Os desvios padrão relativos (n=12) foram £ 4,1 % para as três adições de analito, nas 20 amostras de AEHC.

Ponto de murcha permanente de soja, feijão e plantas daninhas

Objetivou-se neste trabalho determinar o ponto de murcha permanente das culturas da soja e do feijão e de plantas daninhas de grande ocorrência nas áreas agrícolas do Brasil. Os tratamentos foram constituídos por seis espécies, sendo duas cultivadas, Glycine max e Phaseolus vulgaris, e quatro de plantas daninhas - Euphorbia heterophylla (plantas suscetíveis e resistentes a herbicidas inibidores de ALS), Bidens pilosa e Desmodium tortuosum -, com duas épocas de indução de estresse hídrico (pré-florescimento e início do enchimento de grãos). Os solos contidos nos vasos foram mantidos próximos a 80% da capacidade de campo até as épocas predeterminadas para o início do estresse hídrico. A partir desta etapa não foram mais molhadas e, ao primeiro sinal de murcha das espécies, no final do dia, os respectivos vasos foram transferidos para câmara escura, com umidade relativa do ar próxima a 100%, para constatação do não-retorno definitivo da turgidez [ponto de murcha permanente (PMP)]. Nesse ponto, foi coletada uma amostra (sem raízes) do solo para a determinação do teor de água pelo método gravimétrico. A partir dos valores de umidade determinados nas amostras de solo, para cada tratamento avaliado, caracterizou-se, por meio da curva de retenção de umidade do solo, o potencial da água no PMP. Na fase de enchimento de grãos, o PMP das plantas de B. pilosa ocorreu quando o potencial de retenção de água do solo era mais negativo em relação às outras espécies avaliadas, demonstrando que, neste estádio de desenvolvimento, esta espécie apresenta maior eficiência na extração de água do solo e, conseqüentemente, maior potencial competitivo do que as outras avaliadas.

Interferência de capim-arroz (Echinochloa spp.) na cultura do arroz irrigado (Oryza sativa) em função da época de irrigação

A adoção de novos métodos de manejo das plantas daninhas nas lavouras de arroz irrigado, com intuito de minimizar o uso de herbicidas, requer entendimento das relações de interferência entre as plantas daninhas e a cultura. Objetivou-se com trabalho avaliar a influência de épocas de início da irrigação por inundação da lavoura de arroz irrigado e a interferência do capim-arroz na cultura e comparar as variáveis explicativas população de plantas, massa seca aérea, cobertura do solo e área foliar pelas plantas de capim-arroz, visando identificar a que propicia melhor ajuste dos dados ao modelo. Para isso, foi instalado um experimento no ano agrícola 2005/06, em delineamento experimental completamente casualizado, sem repetição. Os tratamentos utilizados foram épocas de início da irrigação: 1, 10 e 20 dias após a aplicação dos tratamentos herbicidas (DAT) e populações de plantas de capim-arroz. As populações de capim-arroz foram de 0, 6, 8, 14, 20, 28, 42, 66 e 200; 0, 4, 6, 50, 66, 88, 92 e 200; e 0, 10, 12, 32, 42, 74, 166, 174 e 178 plantas m-2, para as épocas de entrada de água aos 1, 10 e 20 DAT, respectivamente, perfazendo um total de 26 unidades experimentais. A perda de produtividade de grãos da cultura em função das variáveis explicativas população, massa seca aérea, área foliar e cobertura do solo das plantas de capim-arroz foi relacionada pelo uso de modelo de regressão não-linear da hipérbole retangular. O modelo da hipérbole retangular estima adequadamente as perdas de produtividade da cultura do arroz irrigado pela interferência do capim-arroz. A antecipação da entrada de água na lavoura favorece positivamente a habilidade competitiva das plantas de arroz, cultivar BRS-Pelota, com relação às plantas de capim-arroz. A variável população de plantas apresenta melhor ajuste dos dados ao modelo, comparativamente às demais.

Manejo de plantas de cobertura no controle de plantas daninhas na cultura do milho

O sistema de semeadura direta na cultura do milho tem apresentado expansão na região Sul do Brasil. A escolha adequada de espécies de cobertura, associada ao manejo em pré-semeadura da cobertura, pode intensificar o efeito alelopático sobre plantas daninhas. Foi avaliada a adaptabilidade de espécies vegetais e os efeitos alelopáticos, associados às práticas de manejo da cobertura e ao uso de herbicida pós-emergente, no controle de plantas daninhas na cultura do milho. O delineamento experimental utilizado foi em blocos ao acaso, com quatro repetições. Os tratamentos foram: espécies de cobertura, manejo das coberturas e aplicação ou não de herbicida em pós-emergência. As variáveis avaliadas foram: porcentagem de cobertura, matéria seca da cobertura, número de plantas daninhas, além de estatura, área foliar, matéria seca de plantas de milho e produtividade de grãos. As espécies nabo forrageiro e azevém apresentaram maior cobertura do solo. A cobertura de azevém proporciona maior redução de plantas daninhas e maior crescimento de plantas de milho. A dessecação das culturas de cobertura com glyphosate e paraquat, em geral, reduz o número de plantas daninhas e favorece o crescimento da cultura do milho. A influência do manejo da cobertura de solo na produtividade de grãos depende da espécie utilizada. A aplicação do herbicida nicosulfuron aumentou a produtividade do milho, independentemente da cultura de cobertura ou do manejo adotado.

Regulation of pituitary hormones and cell proliferation by components of the extracellular matrix

The extracellular matrix is a three-dimensional network of proteins, glycosaminoglycans and other macromolecules. It has a structural support function as well as a role in cell adhesion, migration, proliferation, differentiation, and survival. The extracellular matrix conveys signals through membrane receptors called integrins and plays an important role in pituitary physiology and tumorigenesis. There is a differential expression of extracellular matrix components and integrins during the pituitary development in the embryo and during tumorigenesis in the adult. Different extracellular matrix components regulate adrenocorticotropin at the level of the proopiomelanocortin gene transcription. The extracellular matrix also controls the proliferation of adrenocorticotropin-secreting tumor cells. On the other hand, laminin regulates the production of prolactin. Laminin has a dynamic pattern of expression during prolactinoma development with lower levels in the early pituitary hyperplasia and a strong reduction in fully grown prolactinomas. Therefore, the expression of extracellular matrix components plays a role in pituitary tumorigenesis. On the other hand, the remodeling of the extracellular matrix affects pituitary cell proliferation. Matrix metalloproteinase activity is very high in all types of human pituitary adenomas. Matrix metalloproteinase secreted by pituitary cells can release growth factors from the extracellular matrix that, in turn, control pituitary cell proliferation and hormone secretion. In summary, the differential expression of extracellular matrix components, integrins and matrix metalloproteinase contributes to the control of pituitary hormone production and cell proliferation during tumorigenesis.

Feasibility of the use of recycled nutrients in fast growing pulpwood production

The application of pulp and paper mill (PPM) sludge in agriculture and forestry has been acknowledged as soil amendments and a plant nutrient source. The main objectives of this study were to evaluate the total cost of the use of recycled nutrients from PPM sludge in fast growing pulpwood production, and the financial profitability of fast growing pulpwood production with the use of these recycled nutrients. The investment and production costs of fast growing pulpwood plantation were directly acquired from a previous research, while the other data was compiled through different studies. The total cost of the use of PPM sludge was evaluated based on assumed factors. Discounted cash flow method was used to evaluate the financial profitability, using NPV and IRR as indicators. The results of estimated sludge nutrient contents were 16.2 g N, 2.9 g P, and 2.4 g K kg-1 of dry sludge. The sludge application rate was estimated at 1.36 Mg/ha in the first year. The total cost of the use of PPM sludge involved transport and spreading cost of US$49.15/dry ton. The fertilization cost applied in the financial model was designed in 3 different options and their results were as follows: option (1) was taken directly from the reference research (US$97/ha); option (2) was the use of sludge alone (US$66.75/ha); and option (3) was the use of sludge and TSP fertilizer (US$83.80/ha). The average NPV without discounting was US$248,180 while the IRRs ranged between approximately 3-4% with an average of 3.63%. Although option (2) and (3) contributed to higher IRRs compared to option (1), this increase was still not significant as the IRR was not sensitive to the total fertilization cost. The advantages are that this practice can be performed at a lower cost and the application rate can be still increased if necessary. It is better for forest plantations compared to agriculture and consequently supports reforestation program. In addition, it can be similarly applied in wood biomass production. A disadvantage is that the IRRs were not very favorable compared to the criterion of 11%. The sludge high in C:N ratio can cause nitrogen immobilization, and regulatory concerns may restrict and complicate the use of sludge landspreading and contribute to additional costs and processes.

Therapeutic effects of Sophora moorcroftiana alkaloids in combination with albendazole in mice experimentally infected with protoscolices of Echinococcus granulosus

The objective of the present study was to determine if the combination of alkaloids from Sophora moorcroftiana seeds and albendazole might be effective in the treatment of experimental echinococcosisin female NIH mice (6 weeks old and weighing 18-20 g, N = 8 in each group) infected withprotoscolices of Echinococcus granulosus. Viable protoscolices (N = 6 x 103) were cultured in vitro in 1640 medium and mortality was calculated daily. To determine the in vivo efficacy, mice were inoculated intraperitoneally with viable protoscolices and then treated once daily by gavage for three months with the alkaloids (50 mg kg-1 day-1) and albendazole (50 mg kg-1 day-1), separately and in combination (both alkaloids at 25 mg kg-1 day-1 and albendazole at 25 mg kg-1 day-1). Next, the hydatid cysts collected from the peritoneal cavity of the animals were weighed and serum IL-4, IL-2, and IgE levels were analyzed. Administration of alkaloids to cultured protoscolices showed significant dose- and time-dependent killing effects. The weight of hydatid cysts was significantly decreased upon treatment with each drug (P < 0.01), but the decrease was more prominent and the rate of hydatid cyst growth inhibition was much higher (76.1%) in the group receiving the combined treatments (18.3 ± 4.6 mg). IL-4 and total IgE were decreased (939 ± 447 pg/mL and 2.03 ± 0.42 IU/mL, respectively) in serum from mice treated with alkaloids and albendazole compared with the untreated control (1481 ± 619 pg/mL and 3.31 ± 0.37 IU/mL; P < 0.01). These results indicate that S. moorcroftiana alkaloids have protoscolicidal effects and the combination of alkaloids and albendazole has significant additive effects.