Rationale, application and clinical qualification for NT-proBNP as a surrogate end point in pivotal clinical trials in patients with AL amyloidosis

Amyloid light-chain (LC) amyloidosis (AL amyloidosis) is a rare and fatal disease for which there are no approved therapies. In patients with AL amyloidosis, LC aggregates progressively accumulate in organs, resulting in organ failure that is particularly lethal when the heart is involved. A significant obstacle in the development of treatments for patients with AL amyloidosis, as well as for those with any disease that is rare, severe and heterogeneous, has been satisfying traditional clinical trial end points (for example, overall survival or progression-free survival). It is for this reason that many organizations, including the United States Food and Drug Administration through its Safety and Innovation Act Accelerated Approval pathway, have recognized the need for biomarkers as surrogate end points. The international AL amyloidosis expert community is in agreement that the N-terminal fragment of the pro-brain natriuretic peptide (NT-proBNP) is analytically validated and clinically qualified as a biomarker for use as a surrogate end point for survival in patients with AL amyloidosis. Underlying this consensus is the demonstration that NT-proBNP is an indicator of cardiac response in all interventional studies in which it has been assessed, despite differences in patient population, treatment type and treatment schedule. Furthermore, NT-proBNP expression is directly modulated by amyloidogenic LC-elicited signal transduction pathways in cardiomyocytes. The use of NT-proBNP will greatly facilitate the development of targeted therapies for AL amyloidosis. Here, we review the data supporting the use of NT-proBNP, a biomarker that is analytically validated, clinically qualified, directly modulated by LC and universally accepted by AL amyloidosis specialists, as a surrogate end point for survival.Leukemia advance online publication, 2 August 2016; doi:10.1038/leu.2016.191

Potential of silicon fertilization in the resistance of chestnut plants toink disease(Phytophthora cinnamomi)

The European chestnut (Castanea sativa Mill.) is a specie with great economic importance in Europe that have been present for thousands of years. In Portugal, the chestnut helps to maintain a positive trade balance, by contributing to the gross national product (GDP). One of the biggest threats for the chestnut is the ink disease caused by Phytophthoracinnamomi, this disease is problematic to chestnut crop with a damaging impact. Silicon (Si) is classified as a beneficial nutrient, having the ability to make plants more resistant to attacks by pathogens. Studies on the effect of silicon on chestnut are practically non-existent, so the aim of this study was to evaluate the impact of silicon in the resistance of chestnut plants to P. cinnamomi. The plants were treated by 0 mM, 5 mM, 7.5mM and 10 mM SiK® with the analyzed mad at 0, 15 and 30 days after inoculation by P. cinnamomi. These findings showed that the Si-treated plants had higher survival rate resulted from the presence of phytoliths in root tissues, that acted as a mechanical barrier reducing the development of pathogenic structures and they arealso associated with the improvement on antioxidant activity through the increase of CAT and SOD, higher values of total phenols compounds and less oxidative damage. The presence of Si in PDA medium reduced the growth of P. cinnamomi all over the time, presenting high PI. This work shows that the Si fertilization in chestnut plants contributes to increase the resistance against P. cinnamomi infection

Portuguese Pinus nigra J.F. Arnold populations: genetic diversity, structure and relationships inferred by SSR markers

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Avaliação do valor nutritivo de silagens de capim-elefante (Pennisetum purpureum Schum) com diferentes níveis de subproduto da goiaba.

O presente trabalho foi desenvolvido com o objetivo de avaliar o valor nutritivo de silagens de capim elefante contendo diferentes níveis de subproduto do processamento do suco da goiaba (0, 5, 10, 15 e 20%). Utilizou-se o delineamento inteiramente casualizado com 4 repetições. Após 40 dias, os silos (100 x 340mm) foram abertos e determinou-se os teores de matéria seca (MS), proteína bruta (PB), fibra em detergente neutro (FDN), fibra em detergente ácido (FDA), hemicelulose (HC) e valores de pH das silagens. Os teores de MS elevaram com a adição do subproduto da goiaba. Para cada 1% de adição de subproduto observou acréscimo de 0,5 pontos percentuais nos teores de MS. O nível mínimo desejado de MS para se obter boas condições fermentativas foi obtido com adição de 15 de subproduto. Para os teores de PB observou-se que mesmo havendo aumento linear com a adição do subproduto da goiaba o nível mínimo de 7%, requerido para bom funcionamento ruminal não foi atingido. Para os teores de HC e valores de pH não foram observadas diferenças entre as várias silagens avaliadas, porém os valores de pH se mantiveram dentro da faixa tida como ideal (3,8- 4,2). Os teores de FDN e FDA foram alterados com a adição de subprodutos da goiaba, porém as alterações não foram de grande magnitude. Pelos dados obtidos conclui-se que adição de subprodutos da goiaba não prejudica o processo fermentativo das silagens. Evaluation of the nutritious value of silage of capim elefante (Pennisetum purpureum Schum) with different levels of by-product of guava. Abstract: The present work was developed with the objective of evaluating the nutritive value of silage of elephant-grass containing different levels of by-product of the processing of the juice of the guava (0, 5, 10, 15 and 20%). A completely random design with four repetitions was used. After 40 days, the silos (100 x 340mm) were open and it was determined the level of dry matter (DM), crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF), hemi-cellulose (HC) and values of pH of the silage. The level of DM increased with the addition of the by-product of the guava. For each 1% of by-product addition it was observed an increase of 0,5 percentile points in the grade of MS. The desired minimum level of DM to obtain good fermenting conditions was obtained with the addition of 15 of by-product. For the grade of CP it was observed that even having a lineal increase with the addition of the by-product of the guava, the minimum level of 7% required for a good rumination, was not reached. For the grade of HC and pH values were not observed differences among the several evaluated silage, however the pH values stayed within the ideal range (3,8-4,2). The grade of NDF and ADF changed with the addition of by-products of the guava, however these alterations were not of a great magnitude. According to the obtained data it is concluded that addition of byproducts of the guava doesn't harm the fermenting process of the silage

Consumo e digestibilidade aparente da matéria seca de subprodutos da agroindústria processadora de frutas.

O trabalho foi realizado com objetivo de avaliar o valor nutritivo de resíduos de frutas derivados da extração de sucos e polpas. Foram estudados os resíduos de abacaxi, acerola, goiaba, maracujá e melão, devidamente desidratados, até que atingissem teor de umidade entre 13 e 16%. Foram utilizados 20 ovinos SRD, machos e castrados, em delineamento inteiramente casualizado com cinco tratamentos (resíduo das frutas), e quatro repetições. Foram avaliados o consumo de matéria seca (CMS) expresso em: g/animal/dia, %PV e g/UTM (PV0,75), e a digestibilidade da matéria seca(DMS), tendo sido feito a análise de variância e comparação de médias. Os maiores CMS (g/animal/dia, %PV e g/UTM) foram obtidos para os resíduos de goiaba, maracujá e melão. O resíduo de acerola apresentou CMS inferior (P>0,05) a todos os outros estudados. O resíduo de maracujá apresentou DMS superior (P<0,01) aos demais resíduos e os resíduos de acerola e goiaba apresentaram a menor DMS. Portanto, os resíduos de frutas estudados podem ser utilizados na alimentação animal por apresentarem CMS e DMS semelhantes a volumosos de boa qualidade. Voluntary intake and dry matter digestibility of fruit processer agroindustry byproducts. ABSTRACT: The study was conducted to evaluate the nutritional value of residues of the juices and pulps extraction. The residues of pineapple, acerola, guava, passion fruit and melon, were properly dehydrated, until that reached humidity between 13 and 16%. It was used 20 SRD sheeps, males and castrated in complete randomized design with five treatments (fruits residues) and four replications. It was estimaded the dry matter intake (DMI) expressed in: g/animal/day; percentage of body weigth (%BW) and g/BW0.75, and dry matter digestibility (DMD), having been made analysis of variance and average comparisons. The higher DMI (g/animal/day, %BW and g/BW0.75) was reachedto the guava, passion fruit and melon residues. Therefore acerola residue presented lesser DMI than others residues. Passion fruit residue presented higter DMD than all residues studied. The acerola and guava residues presented small DMD. The fruits residues studied can be used in animal feeding, because presented IMD and DMD similar to forages of good quality

Avaliação do valor nutritivo de silagens de capim elefante (Pennisetum purpureum) com diferentes níveis de subproduto da acerola (Malpighia glabra).

Resumo: O presente trabalho foi desenvolvido com o objetivo de avaliar o valor nutritivo de silagens de capim elefante contendo diferentes níveis de subproduto do processamento do suco da acerola (0, 5, 10, 15 e 20%). Utilizou-se o delineamento inteiramente casualizado com 4 repetições. Após 40 dias, os silos (100 x 340mm) foram abertos e determinaram-se os teores de matéria seca (MS), proteína bruta (PB), fibra em detergente neutro (FDN), fibra em detergente ácido (FDA), hemicelulose (HC) e valores de pH das silagens. O nível ideal de matéria seca de 30 a 35% foi alcançado nos níveis de adição de 10, 15 e 20% de subproduto. Com a adição de 10, 15 e 20% de subproduto da acerola, as silagens atingiram valores superiores ao nível mínimo de PB (7%) necessário para um bom funcionamento ruminal. Concluiu-se que a adição do subproduto do processamento da acerola em silagens de capim-elefante melhora os níveis protéicos das mesmas, porém as elevações dos níveis de FDA podem comprometer o valor nutritivo das silagens. [Evaluation of the nutritive value of silage of elephant-grass (Pennisetum purpureum) with different levels of by-product of Malpighia glabra]. ABSTRACT: This study aimed to evaluate the nutritive value of silage of elephant-grass containing different levels of by-product of the processing of the juice of the Malpighia glabra (0, 5, 10, 15 and 20%). A completely random design with four repetitions was used. After 40 days, the silos (100 x 340mm) were open and it was determined the level of dry matter (DM), crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF), hemi-cellulose (HC) and values of pH of the silage. The ideal level of dry matter from 30 to 35% was reached in the levels of addition of 10, 15 and 20% of by-product. With the addition of 10, 15 and 20% of by-product of the Malpighia glabra, the silage reached higher values than the minimum level of CP (7%) necessary for a good rumination. It was concluded that the addition of the by-product of the processing of the Malpighia glabra to the silage of elephant-grass improves their protein level, however the increasing of the levels of ADF can compromise the nutritive value of the silage

Expert Consensus Recommendations for the Suspicion and Diagnosis of Transthyretin Cardiac Amyloidosis

Cardiomyopathy is a manifestation of transthyretin amyloidosis (ATTR), which is an underrecognized systemic disease whereby the transthyretin protein misfolds to form fibrils that deposit in various tissues and organs. ATTR amyloidosis is debilitating and associated with poor life expectancy, especially in those with cardiac dysfunction, but a variety of treatment options have recently become available. Considered a rare disease, ATTR amyloidosis may be more prevalent than thought, particularly in older persons. Diagnosis is often delayed because of a lack of disease awareness and the heterogeneity of symptoms at presentation. Given the recent availability of effective treatments, early recognition and diagnosis are especially critical because treatment is likely more effective earlier in the disease course. The Amyloidosis Research Consortium recently convened a group of experts in ATTR amyloidosis who, through an iterative process, agreed on best practices for suspicion, diagnosis, and characterization of disease. This review describes these consensus recommendations for ATTR associated with cardiomyopathy as a resource to aid cardiologists and others in the recognition and diagnosis of ATTR associated with cardiomyopathy. Included in this review is an overview of red flag signs and symptoms and a recommended diagnostic approach, including testing for monoclonal protein, scintigraphy, or biopsy and, if ATTR associated with cardiomyopathy is identified, TTR genotyping

Comparison between mixed liquors of two side-stream membrane bioreactors treating wastewaters from waste management plants with high and low solids anaerobic digestion

In the last years, biological treatment plants for the previously separated organic fraction from municipal solid wastes (OFMSW) have gained importance. In these processes a liquid effluent (liquid fraction from the digestate and leachate from composting piles), which has to be treated previously to its discharge, is produced. In this paper, the characteristics of the mixed liquor from two full-scale membrane bioreactors treating the effluents of two OFMSW treatment plants have been evaluated in view to study their influence on membrane fouling in terms of filterability. For that, the mixed liquor samples have been ultrafiltrated in an OF laboratory plant. Besides, the effect of the influent characteristics to MBRs and the values of the chemical and physical parameters of the mixed liquors on the filterability have been studied. Results showed that the filterability of the mixed liquor was strongly influenced by the soluble microbial products in the mixed liquors and the influent characteristics to MBR. Permeate flux of MBR mixed liquor treating the most polluted wastewater was considerable the lowest (around 20 L/m(2) h for some samples), what was explained by viscosity and soluble microbial products concentration higher than those measured in other MBR mixed liquor. (c) 2016 Elsevier Ltd. All rights reserved.This work was supported by the URBASER Company. Authors thank personnel of the full-scale MBR plants for providing samples.Zuriaga Agusti, E.; Mendoza Roca, JA.; Bes Piá, MA.; Alonso Molina, JL.; Fernández-Giménez, E.; Alvarez-Requena, C.; Munagorri-Manueco, F.... (2016). Comparison between mixed liquors of two side-stream membrane bioreactors treating wastewaters from waste management plants with high and low solids anaerobic digestion. Water Research. 100:517-525. doi:10.1016/j.watres.2016.05.053S51752510