NT-proBNP and stem cell factor plasma concentrations are independently associated with cardiovascular outcomes in end-stage renal disease hemodialysis patients.

Aims: End-stage renal disease (ESRD) treated by chronic hemodialysis (HD) is associated with poor cardiovascular (CV) outcomes, with no available evidence-based therapeutics. A multiplexed proteomic approach may identify new pathophysiological pathways associated with CV outcomes, potentially actionable for precision medicine. Methods and results: The AURORA trial was an international, multicentre, randomized, double-blind trial involving 2776 patients undergoing maintenance HD. Rosuvastatin vs. placebo had no significant effect on the composite primary endpoint of death from CV causes, nonfatal myocardial infarction or nonfatal stroke. We first compared CV risk-matched cases and controls (n = 410) to identify novel biomarkers using a multiplex proximity extension immunoassay (276 proteomic biomarkers assessed with OlinkTM). We replicated our findings in 200 unmatched cases and 200 controls. External validation was conducted from a multicentre real-life Danish cohort [Aarhus-Aalborg (AA), n = 331 patients] in which 92 OlinkTM biomarkers were assessed. In AURORA, only N-terminal pro-brain natriuretic peptide (NT-proBNP, positive association) and stem cell factor (SCF) (negative association) were found consistently associated with the trial's primary outcome across exploration and replication phases, independently from the baseline characteristics. Stem cell factor displayed a lower added predictive ability compared with NT-ProBNP. In the AA cohort, in multivariable analyses, BNP was found significantly associated with major CV events, while higher SCF was associated with less frequent CV deaths. Conclusions: Our findings suggest that NT-proBNP and SCF may help identify ESRD patients with respectively high and low CV risk, beyond classical clinical predictors and also point at novel pathways for prevention and treatment.

Start-up of an aerobic granular sludge system from stored granules: Evaluating the impact of storage period on biomass activity and stability and the effect of temperature on nitrification and phosphorus removal rates.

Aerobic granular sludge (AGS) has been considered a breakthrough within the wastewater treatment sector. However, the long reactor start-up for the formation of granules is challenging and may hinder the spread of this technology. To circumvent this obstacle, inoculation of the reactors with pre-formed granules from existing plants is an interesting approach. In this context, issues related to biomass storage becomes very relevant. In this study, reactivation of aerobic granular biomass after storage was evaluated in a sequencing batch reactor (SBR) designed for achieving simultaneous organic matter, nitrogen and phosphorus removal. Two different scenarios, short (40 days) and long (180 days) storage periods, were assessed, and their influence on the granules physical properties and bioactivity was addressed. The results revealed that the granules stored for a shorter period showed higher resistance to breakage and underwent smooth color changes. On the other hand, the biomass stored for a longer period acquired a dark color and was more susceptible to disruption during reactivation. The granules stored for 6 months become swollen and exhibited an irregular morphology and fluffy structure within the first days of reactivation. Consequently, their settling properties were adversely affected, and some parameters such as the food-to-microorganism ratio had to be adjusted to prevent granules disintegration. Regarding the bioactivity of important microbial functional groups, COD removal was rapidly restored within a few days of SBR operation with the biomass stored for a shorter period. However, it took longer for the biomass stored for 180 days to reach the same performance observed for the granules stored for 40 days. A similar trend is valid for nitrification. In the experiments with sludge stored for a longer time, it took almost twice as long to reach effluent ammonium concentrations lower than 1 mg NH4+-N L-1 compared to the test using biomass stored for 40 days. Phosphate removal was strongly affected by biomass storage, especially after 180 days of inactivity, a condition found to be detrimental for polyphosphate-accumulating organisms. Finally, cycle tests were also conducted to assess substrate conversion rates for comparison between different trials and evaluate the influence of temperature (10-35 °C) on nitrification and phosphate removal rates.

The varied sources of faculae-forming brines in Ceres' Occator crater emplaced via hydrothermal brine effusion.

Before acquiring highest-resolution data of Ceres, questions remained about the emplacement mechanism and source of Occator crater's bright faculae. Here we report that brine effusion emplaced the faculae in a brine-limited, impact-induced hydrothermal system. Impact-derived fracturing enabled brines to reach the surface. The central faculae, Cerealia and Pasola Facula, postdate the central pit, and were primarily sourced from an impact-induced melt chamber, with some contribution from a deeper, pre-existing brine reservoir. Vinalia Faculae, in the crater floor, were sourced from the laterally extensive deep reservoir only. Vinalia Faculae are comparatively thinner and display greater ballistic emplacement than the central faculae because the deep reservoir brines took a longer path to the surface and contained more gas than the shallower impact-induced melt chamber brines. Impact-derived fractures providing conduits, and mixing of impact-induced melt with deeper endogenic brines, could also allow oceanic material to reach the surfaces of other large icy bodies.

Landslides on Ceres: Diversity and Geologic Context.

Landslides are among the most widespread geologic features on Ceres. Using data from Dawn's Framing Camera, landslides were previously classified based upon geomorphologic characteristics into one of three archetypal categories, Type 1(T1), Type 2 (T2), and Type 3 (T3). Due to their geologic context, variation in age, and physical characteristics, most landslides on Ceres are, however, intermediate in their morphology and physical properties between the archetypes of each landslide class. Here we describe the varied morphology of individual intermediate landslides, identify geologic controls that contribute to this variation, and provide first-order quantification of the physical properties of the continuum of Ceres's surface flows. These intermediate flows appear in varied settings and show a range of characteristics, including those found at contacts between craters, those having multiple trunks or lobes; showing characteristics of both T2 and T3 landslides; material slumping on crater rims; very small, ejecta-like flows; and those appearing inside of catenae. We suggest that while their morphologies can vary, the distribution and mechanical properties of intermediate landslides do not differ significantly from that of archetypal landslides, confirming a link between landslides and subsurface ice. We also find that most intermediate landslides are similar to Type 2 landslides and formed by shallow failure. Clusters of these features suggest ice enhancement near Juling, Kupalo and Urvara craters. Since the majority of Ceres's landslides fall in the intermediate landslide category, placing their attributes in context contributes to a better understanding of Ceres's shallow subsurface and the nature of ground ice.

Impact of reduced exposure to calcineurin inhibitors on the development of de novo DSA: a cohort of non-immunized first kidney graft recipients between 2007 and 2014.

BACKGROUND: In low-immunological risk kidney transplant recipients (KTRs), reduced exposure to calcineurin inhibitor (CNI) appears particularly attractive for avoiding adverse events, but may increase the risk of developing de novo Donor Specific Antibodies (dnDSA). METHODS: CNI exposure was retrospectively analyzed in 247 non-HLA immunized first KTRs by taking into account trough levels (C0) collected during follow-up. Reduced exposure to CNI was defined as follows: C0 less than the lower limit of the international targets for ≥50% of follow-up. RESULTS: During a mean follow-up of 5.0 ± 2.0 years, 39 patients (15.8%) developed dnDSA (MFI ≥1000). Patients with DSA were significantly younger (46.6 ± 13.8 vs. 51.7 ± 14.0 years, p = 0.039), received more frequently poorly-matched grafts (59% with 6-8 A-B-DR-DQ HLA mismatches vs. 34.6%, p = 0.016) and had more frequently a reduced exposure to CNI (92.3% vs. 62.0%, p = 0.0002). Reduced exposure to CNI was associated with an increased risk of dnDSA (multivariable HR = 9.77, p = 0.002). Reduced exposure to CNI had no effect on patient survival, graft loss from any cause including death, or post-transplant cancer. CONCLUSIONS: Even in a low-immunological risk population, reduced exposure to CNI is associated with increased risk of dnDSA. Benefits and risks of under-immunosuppression must be carefully evaluated before deciding on CNI minimization.

In vitro antiviral activity of Lactobacillus casei and Bifidobacterium adolescentis against rotavirus infection monitored by NSP4 protein production.

AIMS: The aim of this study was to determine the antiviral activity of four probiotic metabolites (Lactobacillus and Bifidobacetrium species) against rotavirus in vitro infection monitored by the NSP4 protein production and Ca(2+) release. METHODS AND RESULTS: The antiviral effect of the metabolites was performed due a comparison between a blocking model and an intracelullar model on MA104 cells, with the response of NSP4 production and Ca(2+) liberation measured by flow cytometry. Significant results were obtained with the metabolites of Lactobacillus casei, and Bifidobacterium adolescentis in the reduction of the protein production (P = 0·04 and P = 0·014) and Ca(2+) liberation (P = 0·094 and P = 0·020) in the intracellular model, which suggests a successful antiviral activity against RV infection. CONCLUSIONS: This study demonstrates that probiotic metabolites were able to interfere with the final amount of intracellular NSP4 protein and a successful Ca(2+) regulation, which suggests a new approach to the mechanism exerted by probiotics against the rotavirus infection. SIGNIFICANCE AND IMPACT OF THE STUDY: A novel anti-rotaviral effect exerted by probiotic metabolites monitored by the NSP4 protein during the RV in vitro infection and the effect on the Ca(2+) release is reported; suggesting a reduction on the impact of the infection by decreasing the damage of the cells preventing the electrolyte loss.

Genetic diversity of polysporic isolates of Moniliophthora perniciosa (Tricholomataceae).

The causal agent of witches' broom disease, Moniliophthora perniciosa is a hemibiotrophic and endemic fungus of the Amazon basin and the most important cocoa disease in Brazil. The purpose of this study was to analyze the genetic diversity of polysporic isolates of M. perniciosa to evaluate the adaptation of the pathogen from different Brazilian regions and its association with different hosts. Polysporic isolates obtained previously in potato dextrose agar cultures of M. perniciosa from different Brazilian states and different hosts (Theobroma cacao, Solanum cernuum, S. paniculatum, S. lycocarpum, Solanum sp, and others) were analyzed by somatic compatibility grouping where the mycelium interactions were distinguished after 4-8 weeks of confrontation between the different isolates of M. perniciosa based on the precipitation line in the transition zone and by protein electrophoresis through SDS-PAGE. The diversity of polysporic isolates of M. perniciosa was grouped according to geographic proximity and respective hosts. The great genetic diversity of M. perniciosa strains from different Brazilian states and hosts favored adaptation in unusual environments and dissemination at long distances generating new biotypes.

Nefropatía diabética. Asignatura pendiente / Diabetic nephropathy. a pending subject

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Atividade eletromiografica dos musculos masseter e temporal anterior de criancas com mordida cruzada posterior unilateral (MCPu) / EMG activity os Masseter and Anterior Temporalis muscles in children with unilateral posterior crossbite

A Mordida Cruzada Posterior unilateral (MCPu) pode estar relacionada ao desenvolvimento de alteracoes neuromusculares do sistema estomatognatico. No entanto, um padrao de atividade eletrica da musculatura mastigatoria de criancas com MCPu ainda nao foi determinada na literatura. Objetivo: comparar a atividade eletrica de musculos mastigatorios em criancas com MCPu comparadas a criancas com normoclusao. Metodo: participaram deste estudo seis criancas com MCPu a direita (MCPD: 7,5+-1,87 anos), seis com MCPu a esquerda (MCPE: 7,5+- 1,87 anos) e oito normoclusao (8,14+-2,91 anos). A atividade eletrica dos musculos temporal porcao anterior e masseter bilaterais foi avaliada por meio de eletromiografia de superficie durante a mastigacao habitual e bilateral com frequencia controlada de 0,9 HZ. para analise estatistica foi utilizado o teste de ANOVA (P<-0,05). Resultados: os resultados obtidos demonstraram nao haver diferencas significativas entre os gupos MCPD, MCPE e normoclusao na atividade eletrica dos musculos mastigatorios avaliados nas duas situacoes de mastigacao avaliadas, entretanto, foi observada tendencia de maior atividade dos musculos elevadores homolaterais a mordida cruzada de criancas com MCPu, bem como maior atividade dos musculos masseteres e temporais anteriores direitos, em comparacao aos musculos contralaterais, apenas em cria ncas com MCPD. Conclusao: Esses resultados demonstram nao haver diferencas na atividade eletrica dos musculos mastigatorios de criancas com MCPU. No entanto, a grande variabilidade observada nas criancas com MCPu, principalmente nas criancas com MCPD, pode ser mascarado as diferencas entre os grupos avaliados

Evaluation of biochemical and serological methods to identify and clustering yeast cells of oral Candida species by CHROMagar test, SDS-PAGE and ELISA.

The purpose of this work was to evaluate biochemical and serological methods to characterize and identify Candida species from the oral cavity. The strains used were five Candida species previously identified: C. albicans, C. guilliermondii, C. parapsilosis, C. krusei, C. tropicalis, and Kluyveromyces marxianus, as a negative control. The analyses were conducted through the SDS-PAGE associated with statistical analysis using software, chromogenic medium, and CHROMagar Candida (CA), as a differential medium for the isolation and presumptive identification of clinically important yeasts and an enzyme-linked immunoabsorbent assay (ELISA), using antisera produced against antigens from two C. albicans strains. This method enabled the screening of the three Candida species: C. albicans, C. tropicalis, and C. krusei, with 100% of specificity. The ELISA using purified immunoglobulin G showed a high level of cross-reaction against protein extracts of Candida species. The SDS-PAGE method allowed the clustering of species-specific isolates using the Simple Matching coefficient, S(SM) = 1.0. The protein profile analysis by SDS-PAGE increases what is known about the taxonomic relationships among oral yeasts. This methodology showed good reproducibility and allows collection of useful information for numerical analysis on information relevant to clinical application, and epidemiological and systematical studies.

Evaluation of biochemical and serological methods to identify and clustering yeast cells of oral Candida species by CHROMagar test, SDS-PAGE and ELISA

Este trabalho teve o propósito de avaliar métodos bioquímicos e sorológicos para serem aplicados na caracterização e identificação de linhagens do gênero Candida isoladas da cavidade bucal. As cepas empregadas representam cinco espécies de Candida previamente identificadas: C. albicans, C. guilliermondii, C. parapsilosis, C. krusei e C. tropicalis, utilizando como controle negativo Kluyveromyces marxianus. Foram empregadas as técnicas de gel de poliacrilamida (SDS-PAGE) associado à análise estatística em software, CHROMagar Candida (CA), meio cromogênico diferencial descrito para o isolamento e identificação presuntiva de leveduras de importância clínica e um ensaio de imunoabsorção ligado a enzima (ELISA), utilizando antissoro produzido contra extratos protéicos de uma linhagem-padrão de Candida e um isolado de cavidade oral de C. albicans. O método mostrou-se adequado para a identificação presuntiva de C. albicans, C. tropicalis e C. krusei, com 100% de sensibilidade e especificidade, com base na coloração e textura das colônias. O método de ELISA utilizando imunoglobulinas G purificadas apresentou alto teor de reação cruzada com as outras espécies de Candida estudadas. A análise do perfil protéico por SDS-PAGE permitiu agrupar os isolados da cavidade oral por intermédio do coeficiente "Simple Matching", SSM = 1,0. Os perfis protéicos analisados por SDS-PAGE ampliam os conhecimentos sobre as relaçäes taxonômicas de leveduras isoladas da cavidade oral. Esta metodologia demonstra boa reprodutibilidade e origina informaçäes úteis para aplicação clínica e estudos que envolvem a sistemática e a epidemiologia.

Production of a monoclonal antibody against Aeromonas hydrophila and its application to bacterial identification.

AIMS: to develop a monoclonal antibody (MAb) for the rapid detection of Aeromonas hydrophila in human faeces. METHODS AND RESULTS: A monoclonal antibody with strong specificity against Aer. hydrophila was obtained by the fusion of myeloma cells and splenocytes of a mouse immunized with vegetative cells of Aer. hydrophila ATCC 7966, followed by a two-step selection against other species of the genera. ELISA analyses revealed that MAb 5F3 strongly reacts with all the Aer. hydrophila strains evaluated, showing a just basal reactivity against other species of the genera, especially Aer. sobria and Aer. caviae. CONCLUSIONS: MAb 5F3 was characterized as an IgG that recognized a polypeptide of approximately 110 kDa. SIGNIFICANCE AND IMPACT OF THE STUDY: This MAb could be used to detect Aer. hydrophila in human stool samples.

Psicoterapia psicodinâmica breve: estudo de acompanhamento / Brief psychodynamic psychotherapy: a follow-up study

Foram verificadas mudanças na adaptação e em variáveis psicodinâmicas ao final e no acompanhamento, após seis meses, de psicoterapias psicodinâmicas breves. N=33 (N = 23 mulheres, N = 10 homens, idades entre 21 e 60 anos, média 34,3). Apesar da maioria dos sujeitos apresentar adaptação não eficaz severa no início, as terapias causaram mudanças psicodinâmicas e adaptativas, em parte da amostra, que ainda estavam presentes seis meses após seu término. Mudanças nas estratégias devem ser buscadas, visando os mais comprometidos (AU)

Psicoterapia psicodinâmica breve: estudo de acompanhamento / Brief psychodynamic psychotherapy: a follow-up study

Verifica mudanças na adaptaçäo e em variáveis psicodinâmicas ao final e no acompanhamento, após 6 meses, de psicoterapias psicodinâmicas breves N=33 (N= 23 mulheres, N=10 homens, idades entre 21 e 60 anos, média 34,3). Apesar da maioria dos sujeitos apresentar adaptaçäo näo eficaz severa no início, as terapias causaram mudanças psicodinâmicas e adaptativas, em parte da amostra, que ainda estavam presentes seis meses após seu término. Mudanças nas estratégias devem ser buscadas, visando os mais comprometidos

Regulation of ovarian antioxidant vitamins, reduced glutathione, and lipid peroxidation by luteinizing hormone and prostaglandin F2 alpha.

Reactive oxygen species are generated by the rat ovary, and they evoke marked antigonadotropic responses in ovarian cells. Protection against reactive oxygen species is provided by antioxidants such as vitamins C, E, and A, and reduced glutathione (GSH). Our objectives were to establish the ovarian levels of these antioxidants during development and regression of the corpus luteum of the pseudopregnant rat and to determine whether these levels were changed by an acute treatment with either a luteotropic (LH) or luteolytic (prostaglandin [PG] F2 alpha) agent. In addition, we evaluated the extent of oxidative activity in the ovary by determining the level of lipid peroxidation. Follicular development was associated with a significant increase in ovarian levels of vitamin A and GSH, whereas levels of vitamins E and C were unchanged. During the luteal phase, vitamin E levels tended to increase, whereas vitamin A and GSH levels decreased. Luteal regression was associated with a marked increase in ovarian levels of vitamins E and A, whereas GSH levels increased only transiently. Acute treatment with LH in the midluteal phase produced a transient decrease in vitamin C levels that was maximal at 4 h. Luteal vitamin E levels were markedly increased 24 h after LH treatment, whereas vitamin A levels were unchanged, and no evidence of lipid peroxidation was seen. Acute treatment with PGF2 alpha produced a transient decrease in luteal vitamin C levels coincident with transient lipid peroxidation and a sustained fall in serum progesterone levels. Ovarian vitamin A levels were elevated 24 h after PGF2 alpha treatment.(ABSTRACT TRUNCATED AT 250 WORDS)