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Aim: To determine if vitamin D3 treatment reduced the incidence of vaginal prolapse in pregnant sheep on a North Canterbury sheep breeding property. Methods: Pregnant ewes from a single farm were allocated to three treatment groups in May 2018. At this time, the first group (EarlyVitADE; n = 512) received an I/M 1 mL dose of 500,000 IU/mL vitamin D3, 60,000 IU/mL vitamin A, and 25 mg/mL vitamin E. This was repeated in July 2018, when the second group (LateVitADE; n = 695) also received the same treatment. The third group (n = 737) were untreated controls. All cases of vaginal prolapse on the property were recorded from pregnancy diagnosis in June 2018 until ewes were set-stocked in August 2018. The planned start of lambing was 10 August 2018. Results: During the period of observation, vaginal prolapses were recorded in 3/699 (0.4%) 2-year-old ewes, and the odds of vaginal prolapse were not associated with treatment group in these ewes (p > 0.3). Amongst ewes aged ≥3 years, during the same period, there were 6/333 (1.8%), 6/443 (1.4%) and 25/469 (5.3%) cases in the EarlyVitADE, LateVitADE and control groups, respectively. Compared to control ewes, the odds of vaginal prolapse were reduced in both the EarlyVitADE (OR = 0.37; 95% CI = 0.15–0.92) and LateVitADE (OR = 0.25; 95% CI = 0.10–0.62) treatment groups. Conclusions and clinical relevance: In this preliminary study, administration of injectable vitamins A, D3, and E to pregnant ewes reduced the incidence of vaginal prolapse during the period from pregnancy diagnosis to set-stocking on one North Canterbury hill-country farm. Due to the restricted data collection period, this investigation should be replicated to better quantify the repeatability of the observed treatment effect over the complete lambing period. [ABSTRACT FROM AUTHOR]

Pinhão is highly perishable due to its high water activity, being easily affected by fungi during storage and also susceptible to infestation by larvae. This seed is usually marketed in the pinhão cones itself, or bulk threshed, and packed in plastic bags, chilled or ground frozen. Pinhão conservation and industrialization techniques should be developed to promote its commercialization and consumption at other times of the year, besides the seasonal period, encouraging its sustainable production, extraction and commercialization, considering its essentially extractive character. The objective of this study was to evaluate the conservation of pinhão by the use of gamma radiation and refrigeration. The pinhões were irradiated with a cobalt–60 source at a dose rate of 1 kGy. A non-irradiated sample was used as a control. The pinhões were packed in high-density polyethylene bags and stored at ambient temperature and refrigerated at 4 ºC, during 90 days. Pinhões were evaluated for weight loss, acidity, reducing sugars, vitamin C, firmness, color, total phenolic compounds, antioxidant activity and microbiological analyzes. The isolated use of gamma radiation was not effective for the maintenance of the evaluated parameters. However, when used in conjunction with refrigerated storage, it reduced the growth of aerobic fungi, as well as mesophilic and psychrotrophic microorganisms. The isolated use of refrigeration showed a reduction in weight loss, reducing sugars and an increase in vitamin C content and antioxidant activity. Thus, to increase the benefits, we suggest evaluating higher doses of radiation as a function of the thick pinhão shell.

Apresentação do dossiê "Tecnologia e políticas culturais: o acesso à cultura digital no Brasil", que contempla os seguintes artigos: “Iniciativas brasileiras em torno da construção de uma Política Nacional para Acervos Digitais de Instituições de Memória: o desafio da memória em tempos de cultura digital”; “As Transformações da Era Digital e o Impacto na Economia da Cultura do Livro”; “Dialogando com e sobre o rural através das novas mídias: estratégias e desafios da comunicação” e “Softwares livres e políticas culturais no Brasil: o caso do Mapa Cultural”. Os artigos tratam das aplicações das tecnologias digitais às políticas culturais, localizando-as num contexto mais geral das aplicações das TICs e analisando casos setoriais.

Este trabalho tem como objeto a expansão do consumo cultural-digital das famílias brasileiras nos últimos dez anos. Tal expansão implicou diretamente a elevação de seus gastos orçamentários com cultura. De acordo com o IBGE, em 2009, as famílias brasileiras dispenderam em média 5% do seu orçamento mensal com bens culturais. Caso os serviços de telefonia e comunicação fossem adicionados à rubrica cultura, essa mesma média de gastos saltaria para 8,6%. Em face do aumento da produção, distribuição e consumo dos serviços culturais-digitais (séries, filmes, músicas, games, etc.) por meio dos dispositivos digitais móveis, notadamente os smartphones, sustentamos que a metodologia de cálculo e aferição do IBGE exige uma revisão. Para sustentar tal necessidade, demonstramos que os mercados culturais passam por uma profunda mudança: a digitalização do simbólico.

In the last decades, the themes of creative economy, creative industries and creative cities served as a technical and operational fundament for the formulation and execution of a series of economic development public policies. The main actors of this profusion and legitimation of power were the economists, managers and business schools theorists in close relation to national governments and UN agencies. This process was possible due to the emergence of post-industrial societies, the expansion of the knowledge economy and the digitalization of cultural markets. The combination of these three aspects produced a structural approximation between the symbolic-aesthetic domain and the economic-technological domain, resulting in the formation of native categories, such as creative economy, creative industries and creative cities. These categories do not have the analytical and descriptive potential which able to comprehend and explain the new relations between those domains, tough they are themselves a result of these new relations.

This work investigates the process of competition between some of the most important technology companies in the world, which created business models aimed at the culturaldigital services market - series, movies, games, music, books and animation. It is a process of global scope and great economic, technological and creative impact, which has been refashioning the cultural markets through the intense process of digitalization and corporate action. To analyze these aspects, two methodological and analytical strategies were adopted simultaneously along the text. The first one sought to use the concepts of digitalization of the symbolic and cultural-digital capitalism, both of which are woven into other works and research that combine a broader research agenda, whose efforts are engaged in the realization of an economic sociology of cultural markets. The second was to explore the latest economic decisions and commercial and creative strategies adopted by the Netflix, Disney and Apple companies, as well as to update data on the expansion of consumption of digital artistic-cultural content, especially in Brazil.

neste trabalho buscaremos reconstruir o início do mercado brasileiro da internet. Para isso partiremos de matérias publicadas em sites de naturezas distintas, no período dos 15 anos iniciais do mercado da internet no Brasil. Essas notícias são importantes porque trazem questões situadas no tempo sobre o uso da internet por parte dos brasileiros, bem como o esforço do Estado na criação e controle do mercado da internet. Ainda, traremos dilemas que preocuparam os sujeitos nesse período, seja do ponto de vista dos impactos da internet e da tecnologia na vida de seus usuários, ou dos dispositivos jurídicos necessários para a proteção dos sujeitos no cotidiano da relação com a internet. Esses dados serão mobilizados na operacionalização de diferentes teorias da rede que estão em disputa no campo de produção de conhecimento da sociologia, os representantes são Castells, Elias, Granovetter e Latour. Dessa forma, através dessas teorias, iremos desnaturalizar as preocupações relacionadas ao uso da internet no Brasil, bem como relembrar que as questões que nos afligem hoje, na verdade, são antigas.

To understand the relevance of the new media in the formation of the indignation nets, this text, of exploratory stamp, debates the digital activism in contemporary Brazil . Methodologically, we will make a discussion on cyberactivism, digital media, and national pressure groups starting from two examples, Movimento Brasil Livre (The Free Brazil Movement) and Vem pra Rua (Come to The Street movement) – these are key movements in the organisation of the big anti-government mobilisation that took place in 2015–2016 in Brazil. The theme is important because it embraces current and future challenges of the digital activism, once that this field faced significant changes in the last decades, with the development of interactive media and the technological convergence.

O Serviço Brasileiro de Apoio às Micro e Pequenas Empresas (SEBRAE) tem executado uma série de ações de estímulo ao empreendedorismo cultural. O SEBRAE é uma entidade privada sem fins lucrativos e de interesse público, com fortes vínculos jurídicos, financeiros e políticos junto ao Estado brasileiro. A atuação do SEBRAE no âmbito do empreendedorismo cultural o torna um agente estatal de mercado (AEM) bastante específico, cuja atuação o caracteriza como um agente das novas políticas culturais no Brasil, as políticas econômico-culturais. Por meio das suas modalidades de atuação, o SEBRAE corrobora diretamente para o processo de incorporação das disposições práticas que orientam a formulação de novos modelos de negócios e de novas racionalidades empresariais por parte das micro e pequenas empresas culturais.

A discordance between sex hormone-binding globulin (SHBG) measurements by 2-site ELISAs was investigated using pairings of various "in house" SHBG antibodies together with a concordant control. The 2-site monoclonal ELISAs used the same base coat (11F11) and discordance was observed with one top coat monoclonal antibody (7H9) and also when a polyclonal SHBG antibody was paired with the basecoat antibody (11F11). Sialidase treatment of the discordant sample and purified SHBG revealed increased levels using 7H9 whereas there was no change in SHBG in the concordant sample. Conversely, following sialidase treatment, the discordant sample showed no change in SHBG measured using the other monoclonal antibody pairings whereas the SHBG levels in the concordant sample declined following sialidase using the same monoclonal antibody pairings. This implicated glycosylation as a factor in antibody recognition and synthetic peptides spanning the two N-linked and one O-linked glycosylation regions showed that SHBG recognition by monoclonal antibody 7H9 could be disrupted by a peptide spanning the O-linked glycosylation site. Hence rather than immunoassay discordance being attributed to heterophile antibodies or other circulating antibodies here it can be likely attributed to glycosylation affecting antibody recognition and hence the measurement of SHBG., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: Supplementation provides the best means of improving vitamin D status; however, individual responses vary partly owing to genetics. The aim of this study was to determine whether 28 single nucleotide polymorphisms (SNPs) in six key vitamin D pathway genes (GC, DHCR7, CYP2 R1, CYP24 A1, CYP27 B1, VDR) were associated with differences in response to supplementation., Methods: Participants (N = 313; n = 160 vitamin D, n = 153 placebo) were part of VIDARIS (Vitamin D and Acute Respiratory Infections Study), a double-blind, randomized controlled trial involving oral monthly supplementation of either vitamin D 3 (200 000 IU each for the first 2 mo, thereafter 100 000 IU monthly) or placebo for 18 mo. Circulating 25-hydroxyvitamin D (25[OH]D) concentrations at baseline and 2, 6, 12, and 18 mo, and vitamin D binding protein (Gc-globulin) and calculated free 25(OH)D concentrations at baseline and 2 mo were obtained. Multiple regression was used to model associations between genetic variants and 25(OH)D, Gc-globulin, and free 25(OH)D concentrations., Results: SNPs within GC, CYP2 R1, and CYP27 B1 were associated with 25(OH)D concentrations following supplementation. However, only two GC gene SNPs (rs2282679, rs1155563) were significant after adjustment for multiple testing. This effect disappeared after more than 2 mo of supplementation. None of the SNPs were significantly associated with Gc-globulin concentrations; however, there was a significant interaction with one SNP in DHCR7 (rs12785878), which was associated with reduced free 25(OH)D concentrations in the supplemented arm., Conclusion: Only variants of GC were associated with 25(OH)D concentrations after supplementation. This effect was modest and disappeared after >2 mo of supplementation, suggesting it may be time/dose-dependent and saturable., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Calprotectin, the major neutrophil protein, is a critical alarmin that modulates inflammation and plays a role in host immunity by strongly binding trace metals essential for bacterial growth. It has two cysteine residues favourably positioned to act as a redox switch. Whether their oxidation occurs in vivo and affects the function of calprotectin has received little attention. Here we show that in saliva from healthy adults, and in lavage fluid from the lungs of patients with respiratory diseases, a substantial proportion of calprotectin was cross-linked via disulfide bonds between the cysteine residues on its S100A8 and S100A9 subunits. Stimulated human neutrophils released calprotectin and subsequently cross-linked it by myeloperoxidase-dependent production of hypochlorous acid. The myeloperoxidase-derived oxidants hypochlorous acid, taurine chloramine, hypobromous acid, and hypothiocyanous acid, all at 10 μM, cross-linked calprotectin (5 μM) via reversible disulfide bonds. Hypochlorous acid generated A9-A9 and A8-A9 cross links. Hydrogen peroxide (10 μM) did not cross-link the protein. Purified neutrophil calprotectin existed as a non-covalent heterodimer of A8/A9 which was converted to a heterotetramer - (A8/A9) 2 - with excess calcium ions. Low level oxidation of calprotectin with hypochlorous acid produced substantial proportions of high order oligomers, whether oxidation occurred before or after addition of calcium ions. At high levels of oxidation the heterodimer could not form tetramers with calcium ions, but prior addition of calcium ions afforded some protection for the heterotetramer. Oxidation and formation of the A8-A9 disulfide cross link enhanced calprotectin's susceptibility to proteolysis by neutrophil proteases. We propose that reversible disulfide cross-linking of calprotectin occurs during inflammation and affects its structure and function. Its increased susceptibility to proteolysis will ultimately result in a loss of function., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

The measurement of vitamin D-binding protein (VDBP) by immunoassay has been confounded by variable antibody recognition of the Gc1s, Gc1F and Gc2 phenotypes. This has led to spurious conclusions regarding vitamin D status in different ethnic groups. In order to overcome these problems there is a requirement for VDBP antibodies that are unaffected by phenotype status. Here we report the generation and testing of three monoclonal antibodies to VDBP which recognise linear epitopes and are unaffected by vast molar excesses of synthetic peptides spanning these phenotypic domains. These IgG1 kappa antibodies were purified and biotinylated to allow suitable pairings to develop a sandwich ELISA for circulating VDBP. The VDBP ELISA is unaffected by actin and confirms that VDBP levels are significantly reduced in sepsis patients and non-sepsis intensive care patients compared to normal healthy subjects. Levels of VDBP along with total 25OH vitamin D3 can be used to calculate free 25OH vitamin D3 levels and these compare well with consensus values determined independently. The VDBP ELISA meets acceptable performance criteria and as such can be used in conjunction with total 25OH vitamin D3 to determine the free 25OH vitamin D3 status in various cohorts., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The aim of this study was to determine if serum fibroblast growth factor (FGF23) concentrations were increased in dogs with chronic kidney disease (CKD). Serum samples submitted to a commercial laboratory were collected over a 15-month period, 14 samples were from dogs with a history of polyuria/polydipsia, azotaemia and low urine specific gravity, 20 samples were from non-azotaemic dogs. Serum FGF23, parathyroid hormone, total calcium and phosphorus, urea and creatinine were measured. Mann-Whitney test was used to determine differences between non-azotaemic and CKD groups; a one-way ANOVA with Tukey pairwise comparisons was used to determine any differences between International Renal Interest Society stages; and regression models were used to determine predictors of International Renal Interest Society stage, serum phosphorus and FGF23 concentrations. The median serum FGF23 concentration of dogs with CKD was 5194.6pg/mL, which was significantly greater (P<0.001) than the median serum FGF23 concentration of non-azotaemic dogs (259.2pg/mL). Log serum FGF23 and age were significantly associated with IRIS stage (P=0.027 and P=0.032 respectively), while log serum phosphorus concentration (P<0.001) was significantly associated with log serum FGF23 concentration. In summary, serum FGF23 concentration is increased in dogs with CKD, and is associated with serum phosphorus concentration. This phosphatonin pathway may be a useful target for the development of future treatments to control plasma phosphorus concentrations in chronic kidney disease., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Corticosteroid-binding globulin (CBG) binds most of the cortisol in circulation and is a non-functional member of the family of serine protease inhibitors (serpins) with an exposed elastase sensitive reactive centre loop (RCL). The RCL can be cleaved by human neutrophil elastase, released from activated neutrophils, and can also be cleaved at nearby site(s) by elastase released by Pseudomonas aeruginosa, and at two further sites, also within the RCL, by bovine chymotrypsin. Cleavage of the RCL results in a conformational change accompanied by a marked decrease in affinity for cortisol and hence its release at the site of proteolysis. These cleavages are irreversible and the similar half-lives of cleaved and intact CBG could mean that there may be some advantage in slowing the rate of CBG cleavage in acute inflammation thereby increasing the proportion of intact CBG in circulation. Here we show, for the first time, that pre-incubation of tethered human CBG with two monoclonal antibodies to the RCL of CBG protects against cleavage by all three enzymes. Furthermore, in plasma, pre-incubation with both RCL monoclonal antibodies delays neutrophil elastase cleavage of the RCL and one of these RCL monoclonal antibodies also delays bovine chymotrypsin cleavage of the RCL. These findings may provide a basis and rationale for the concept of the use of RCL antibodies as therapeutic agents to effectively increase the proportion of intact CBG in circulation which may be of benefit in acute inflammation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Corticosteroid-binding globulin (CBG) is the predominant carrier of cortisol in circulation and is a non-inhibitory member of the serpin superfamily of serine protease inhibitors. In the stressed or "S" conformation, CBG possesses an intact exposed reactive centre loop (RCL) that can be irreversibly cleaved by elastase released from activated human neutrophils whereupon it adopts a relaxed or "R" conformation. The latter conformation has decreased affinity for cortisol, allowing the release of the majority of cortisol at sites of inflammation. Recently there has been speculation that mild increments in heat such as found in pyrexia (39-40°C) may also induce a reversible "flip-flop" of the RCL into the body of the protein structure, without cleavage, facilitating a reversible temperature-dependent release of cortisol. Here we raised a new monoclonal antibody to the RCL of human CBG and used this in concert with an existing RCL antibody and show by surface plasma resonance that, at temperatures up to 40°C, the RCL of purified CBG and the RCL of CBG in intact plasma is accessible to these two antibodies. Together, the epitopes of these antibodies span 11 consecutive amino acids (STGVTLNLTSK) of the 18 residues of the RCL. This adequate antibody cover of the RCL sequence leads to the conclusion that the proposed temperature-dependent "flip-flop" of the RCL of CBG is doubtful., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Corticosteroid-binding globulin (CBG) is a non-inhibitory member of the serpin superfamily of serine protease inhibitors and carries the majority of cortisol in circulation. It can be cleaved by neutrophil elastase at its exposed reactive centre loop which decreases its affinity for cortisol allowing the release of most of the cortisol at sites of inflammation. Intact and elastase cleaved CBG can be distinguished from each other and can coexist in circulation but with unknown half-lives. Here we treated a portion of purified human CBG with elastase, terminated the digestion and then combined this portion with intact human CBG and measured their respective half-lives in rabbits by ELISA. This investigation shows for the first time that the half-lives of intact and elastase cleaved CBG are identical (∼10h). This is an important finding as it implies that in conditions such as sepsis and septic shock where levels of intact CBG are low and the proportion of cleaved CBG is high that this is likely sustained which may affect the CBG mediated targeted delivery of cortisol to sites of inflammation. Furthermore the residual binding of cortisol to cleaved CBG may alter the overall buffering capacity of CBG for cortisol resetting the baseline concentration of free cortisol., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Extraction followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis is the method of choice when it comes to the accurate quantification of 25-OH-vitamin D in blood samples. It is generally assumed that the addition of exogenous internal standard allows for the determination of the endogenous analyte concentration. In this study we investigated the extraction properties of endogenous and exogenous 25-OH-vitamin D., Methods: Eight samples were used for the evaluation of the extraction procedure and 59 patients' samples for a method comparison. The methanol-to-sample ratio (v/v) and the sample-to-hexane ratio (v/v) were varied and the LC-MS/MS signals of endogenous 25-OH-vitamin D3, spiked 25-OH-vitamin D2 and internal standard of the extracts recorded. The optimized 'in-house' LC-MS/MS assay was compared to two automated chemiluminescence immunoassays from DiaSorin and Abbott., Results: Mathematical analysis of the data revealed a differential extraction of endogenous 25-OH-vitamin D3, spiked 25-OH-vitamin D2 and non-equilibrated internal standard. Exogenous 25-OH-vitamin D can be measured accurately if a definite methanol-to-sample ratio is used. Endogenous 25-OH-vitamin D is affected by critical quantification issues due to a differential slope in the extraction profile. The actual 25-OH-vitamin D concentration can be one-third above the measured extractable concentration. Results confirm that the 'in-house' LC-MS/MS assay provides reproducible 25-OH-vitamin D results., Conclusions: Discordant concentrations of 25-OH-vitamin D from LC-MS/MS assays can be caused by selection of suboptimal extraction conditions. Furthermore, a different sample pretreatment or solvent extraction system may result in a different dissociation and extraction yield of endogenous 25-OH-vitamin D and therefore contribute to variations of LC-MS/MS results., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)