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Recent years have seen an exponential increase in the variety of healthcare data captured across numerous sources. However, mechanisms to leverage these data sources to support scientific investigation have remained limited. In 2013 the Pediatric Heart Network (PHN), funded by the National Heart, Lung, and Blood Institute, developed the Integrated CARdiac Data and Outcomes (iCARD) Collaborative with the goals of leveraging available data sources to aid in efficiently planning and conducting PHN studies; supporting integration of PHN data with other sources to foster novel research otherwise not possible; and mentoring young investigators in these areas. This review describes lessons learned through the development of iCARD, initial efforts and scientific output, challenges, and future directions. This information can aid in the use and optimisation of data integration methodologies across other research networks and organisations.
Circulating cell-free DNA (cfDNA) consists of small fragments of DNA that circulate freely in the bloodstream. In cancer patients, a fraction of cfDNA is derived from tumour cells, therefore containing the same genetic and epigenetic alterations, and is termed circulating cell-free tumour DNA. The potential use of cfDNA, the so-called ‘liquid biopsy’, as a non-invasive cancer biomarker has recently received a lot of attention. The present review will focus on studies concerning the potential clinical applications of cfDNA in ovarian cancer patients.
The goal of this study was to analyse the spatial pattern of tuberculosis (TB) mortality using different approaches, namely: mortality rates (MR), spatial relative risks (RR) and Bayesian rates (Global and Local) and their association with human development index (HDI), Global and its three dimensions: education, longevity and income. An ecological study was developed in Curitiba, Brazil based on data from Mortality Information System (2008–2014). Spatial scan statistics were used to compute RR and identify high-risk clusters. Bivariate Local Indicator of Spatial Associations was used to assess associations. MR ranged between 0 and 25.24/100.000 with a mean (standard deviation) of 1.07 (2.66). Corresponding values for spatial RR were 0–27.46, 1.2 (2.99) and for Bayesian rates (Global and Local) were 0.49–1.66, 0.90 (0.19) and 0–6.59, 0.98 (0.80). High-risk clusters were identified for all variables, except for HDI-income and Global Bayesian rate. Significant negative spatial relations were found between MR and income; between RR and HDI global, longevity and income; and Bayesian rates with all variables. Some areas presented different patterns: low social development/low risk and high risk/high development. These results demonstrate that social development variables should be considered, in mortality due TB.
High concentrations of indium (In) and selenium (Se) have been reported in the Neves-Corvo volcanic-hosted massive sulfide deposit, Portugal. The distribution of these ore metals in the deposit is complex as a result of the combined effects of early ore-forming processes and late tectonometamorphic remobilization. The In and Se contents are higher in Cu-rich ore types, and lower in Zn-rich ore types. At the deposit scale, both In and Se correlate positively with Cu, whereas their correlations with Zn are close to zero. This argues for a genetic connection between Cu, In and Se in terms of metal sourcing and precipitation. However, re-distribution and re-concentration of In and Se associated with tectonometamorphic deformation are also processes of major importance for the actual distribution of these metals throughout the whole deposit. Although minor roquesite and other In-bearing phases were recognized, it is clear that most In within the deposit is found incorporated within sphalerite and chalcopyrite. When chalcopyrite and sphalerite coexist, the In content in sphalerite (avg. 1400 ppm) is, on average, 2–3 times higher than in chalcopyrite (avg. 660 ppm). The In content in stannite (avg. 1.3 wt.%) is even higher than in sphalerite, but the overall abundance of stannite is subordinate to either sphalerite or chalcopyrite. Selenium is dispersed widely between many different ore minerals, but galena is the main Se-carrier. On average, the Se content in galena is ~50 times greater than in either chalcopyrite (avg. 610 ppm) or sphalerite (avg. 590 ppm). The copper concentrate produced at Neves-Corvo contains very significant In (+Se) content, well above economic values if the copper smelters recovered it. Moreover, the high In content of sphalerite from some Cu-Zn ores, or associated with shear structures, could possibly justify, in the future, a selective exploitation strategy for the production of an In-rich zinc concentrate.
In Chiapas, México, natural vegetation is often used for grazing cattle. Local knowledge identify several plants and fruits as been consumed by cattle, But few information is available on their nutritive value. The objective of the present work was to assess the potential nutritive value and biological activity of tannins in 14 materials by means of the in vitro gas production technique.
With the release of dicamba-resistant crops, it is necessary to understand how technical and environmental conditions affect the application of dicamba. This study sought to evaluate drift from dicamba applications through flat-fan nozzles, under several wind speeds in a wind tunnel. Dicamba applications were performed through two standard (XR and TT) and two air induction (AIXR and TTI) 110015 nozzles at 0.9, 2.2, 3.6 and 4.9 ms−1 wind speeds. The applications were made at 276 kPa pressure and the dicamba rate was 561 g ae ha-1. The droplet spectrum was measured using a laser diffraction system. Artificial targets were used as drift collectors, positioned in a wind tunnel from 2 to 12 m downwind from the nozzles. Drift potential was determined using a fluorescent tracer added to solutions, quantified by fluorimetry. The air induction TTI nozzle produced the lowest percentage of dicamba drift at 2.2, 3.6 and 4.9 ms−1 wind speeds at all distances. Dicamba spray drift from XR, TT and AIXR nozzles increased exponentially as wind speed increased, whereas from TTI nozzle drift increased linearly as wind speed increased. Drift did not increase linearly as the volume percentage of droplets smaller than 100 µm and wind speed increased.
The present study investigated the patterns of microorganisms in an artificial larval diet during Dacus ciliatus (Diptera; Tephritidae) larval development. Microbial population contents in the diet of total heterotrophic bacteria, yeast and molds, coliform and lactobacilli, and their dynamics during development, were monitored. Initially, the microbial composition in diet trays failing to produce viable pupae and in trays successfully producing pupae and adult flies was characterized. The failing diet trays contained large populations of lactobacilli that increased during larval development, and low populations of coliforms. In contrast, the successful diet showed an increasing population of coliforms and a low, or undetected, population of lactobacilli. To study the hypothesis that lactobacilli affect D. ciliatus larval development, we conducted controlled inoculation experiments in which Lactobacillus plantarum was added into fresh diet at the time of egg seeding. L. plantarum inoculated trays showed no production of D. ciliatus. Control trays without lactobacilli inoculation showed variable results. One tray successfully produced viable pupae and adults, and showed a slight and slow increase in the indigenous populations of lactobacilli. The second tray, however, failed to produce pupae and showed a fast increase of the indigenous lactobacilli to very high levels. Monitored pH trends in L. plantarum-inoculated diet showed a sharp pH decrease during the first 4 days of larval development from 5 to less than 4 units, while successful diet, producing viable D. ciliatus pupae and adults, showed a moderate pH drop during most of the larval development period. The paper discusses the possible ecological interactions between D. ciliatus larvae, the microbial content of the diet and the physical properties of the diet. The discussion also points out at the usefulness of this approach in understanding and managing mass production parameters of tephritid fruit flies industrial diets used for Sterile Insect Technique.
This study evaluates the morbidity, mortality, and cost differences between patients who underwent either a simple or a complex arterial switch operation.
A retrospective study of patients undergoing an arterial switch operation at a single institution was performed. Simple cases were defined as patients with d-transposition of the great arteries with usual coronary anatomy or circumflex artery originating from the right with either intact ventricular septum or ventricular septal defect. Complex cases included all other forms of coronary anatomy, aortic coarctation or arch hypoplasia, and Taussig–Bing anomalies. Costs were acquired using an institutional activity-based accounting system.
A total of 98 patients were identified, 68 patients in the simple group and 30 in the complex group. The mortality rate was 2% for the simple and 7% for the complex group, p=0.23. Major morbidities including cardiac arrest, extracorporeal membrane oxygenation, a major coronary event, surgical or catheter-based re-intervention, stroke, or permanent pacemaker placement, non-cardiac surgical procedures, mediastinitis, and sepsis did not differ between the simple and complex groups (16 versus 27%, p=0.16). The complex group had increased bleeding requiring re-exploration (0 versus 10%, p=0.04). Hospital and ICU length of stay did not differ. Complex patients had higher overall hospital costs (simple $80,749 versus complex $97,387, p=0.01) and higher postoperative costs (simple $60,192 versus complex $70,132, p=0.02). The operating room and supplies accounted for the majority of the cost difference.
Complex arterial switches can be safely performed with low rates of morbidity and mortality but at an increased cost.
By using an experimental model of dexamethasone-induced osteoporosis we investigated the effects of different therapeutic schemes combining sodium alendronate (SA) and simvastatin on bone mineral and protein composition, microstructural and mechanical remodeling. Wistar rats were randomized into eight groups: G1: non-osteoporotic; G2: osteoporotic; G3, G4, and G5: osteoporotic+SA (0.2, 0.4, and 0.8 mg/kg, respectively); G6, G7, and G8: osteoporotic+SA (0.2, 0.4, and 0.8 mg/kg, respectively)+simvastatin (0.4, 0.6, and 1 mg/kg, respectively). Osteoporosis was induced by dexamethasone (7 mg/kg, i.m.) once a week for 5 weeks. All treatments were administered for 8 weeks. Dexamethasone increased serum levels of alkaline phosphatase, calcium, phosphorus, and urea, especially in non-treated animals, which showed severe osteoporosis. Dexamethasone also induced bone microstructural fragility and reduced mechanical resistance, which were associated with a marked depletion in mineral mass, collagenous and non-collagenous protein levels in cortical and cancellous bone. Although SA has attenuated osteoporosis severity, the effectiveness of drug therapy was enhanced combining alendronate and simvastatin. The restoration in serum parameters, organic and inorganic bone mass, and mechanical behavior showed a dose-dependent effect that was potentially related to the complementary mechanisms by which each drug acts to induce bone anabolism, accelerating tissue repair.
We performed two different approaches (broth enrichment step prior to culture (BEC) and PCR (BEPCR)) for detecting Streptococcus pneumoniae from nasopharyngeal specimens collected from 242 children aged <6 years attending one hospital (n = 140) and one childcare centre (n = 102) in a major urban area in Brazil. These specimens were collected immediately before the introduction of the 10-valent pneumococcal conjugate vaccine (PCV10) and the 13-valent vaccine (PCV13) for routine use in Brazil. Results were compared with previous findings obtained with direct culture (DC) on a selective medium. Colonisation prevalence was 58·3% (n = 141), being higher among children attending the childcare centre (62·7% vs. 55%). The culture-based methods (DC and BEC) enabled the detection of S. pneumoniae in 119 (49·2%) and 115 (47·5%) children, respectively. The PCR-based method (BEPCR) was more sensitive and 137 (56·6%) carriers were identified. Twenty-six serogroups/serotypes were identified, predominantly 6B, 19F, 14, 6A, 15C and 23F. Multiple colonisation was observed in 13 (5·4%) children. The estimated serotypes coverage of available PCVs was 40·4% for the 10-valent (included in the Brazilian immunisation programme) and 55·8% for the 13-valent (only available in private clinics). The use of robust approaches to obtain a more realistic insight about the asymptomatic carrier status is of paramount importance to estimate and assess the impact of vaccine implementation. The combination between culture-based and molecular methods constitutes a suitable strategy.
Analysing the stability and adaptation of cultivars to different environments is always necessary before recommending them for planting on large areas. Additive main effects and multiplicative interaction (AMMI) models have been used to analyse genotype-by-environment interactions (G × E). AMMI models require data with homogeneous variance, normal errors and additive effects. However, agronomic data do not always conform to these statistical assumptions. The objective of the present study was to analyse G × E interactions for severity and incidence of grey leaf spot, a foliar disease in maize caused by Cercospora zeae-maydis, using a generalized AMMI model. Data were collected and evaluated for 36 maize cultivars from experiments carried out in nine Brazilian regions in 2010/11 by the Empresa Brasileira de Pesquisa Agropecuária (EMBRAPA – Milho e Sorgo). Only two of three stable genotypes defined by a quasi-likelihood model with a logistic link function could be recommended for their desirable agronomic characteristics. Four growing locations in which the genotypes were stable were identified, but in only one of these was stability associated with very severe grey leaf spot disease. Cultivars adapted to specific locations with low percentage disease severity were also identified.
Clinical manifestations of acute bronchiolitis (AB) vary from minimal disease to severe respiratory failure. The response to respiratory viral infections is possibly influenced by genetic polymorphisms linked to the regulation of the inflammatory response. In the present study, we investigated whether interleukin-8 (IL-8) and interleukin-17 (IL-17) genetic variants are associated with the severity of AB. A group of Brazilian infants hospitalized with AB and a control group (infants with no or mild AB, without hospitalization) were genotyped for four IL-8/IL-17 variations. For replication, we studied an Argentinean population sample of infants with mild and severe AB. IL-8 polymorphism (rs 2227543) and IL-17 (rs2275913) variants showed significant associations with the severity of AB. The effect of the IL-8 variation could be replicated in the Argentinean sample. This finding suggests that IL-8 variations may influence the severity of AB in young infants. Further genetic association studies in low- or middle-income populations are necessary with the aim of expanding knowledge in this area.
The aim of this study was to evaluate the effect of dietary lysine on performance, protein deposition and respiratory chain gene expression in male broilers. A total of 252 Cobb 500 broilers were distributed, in a completely randomized design, into four treatments with seven replicates of nine birds per experimental unit. Experimental treatments consisted of diets based on corn and soybean meal, with four levels of digestible lysine: 1.016%, 1.099%, 1.182% and 1.265%. The increase in the level of digestible lysine in the diet provided higher weight gains, feed efficiency and body protein deposition. Birds fed the lowest level of dietary lysine (1.016%) showed a lower expression of genes such as NADH dehydrogenase subunit I (ND1), cytochrome b (CYTB) and cytochrome c oxidase subunits I (COX I), II (COX II) and III (COX III), displaying the worst performance and body protein deposition. This demonstrates the relationship existing between the expression of the evaluated genes and the performance responses. In conclusion, results indicate that broilers fed diets with higher levels of digestible lysine have increased messenger RNA expression of some genes coded in the mitochondrial electron transport chain (ND1, CYTB, COX I, COX II and COX III). It may be stated that diets with proper levels of digestible lysine, within the ‘ideal protein’ concept, promote the expression of genes, which increases the mitochondrial energy, thereby fostering body protein deposition and the performance of broilers in the starter phase.
The aim of the present work was to investigate birefringence and morphology of the secretory-stage enamel organic extracellular matrix (EOECM), and structural and mechanical properties of mature enamel of upper incisors from adult rats that had been treated with pamidronate disodium (0.5 mg/kg/week for 56 days), using transmitted polarizing and bright-field light microscopies (TPLM and BFLM), energy-dispersive X-ray (EDX) analysis, scanning electron microscopy (SEM) and microhardness testing. BFLM showed no morphological changes of the EOECM in pamidronate and control groups, but TPLM revealed a statistically significant reduction in optical retardation values of birefringence brightness of pamidronate-treated rats when compared with control animals (p<0.01). EDX analysis showed that pamidronate-induced statistically significant decrease in phosphorus’ quantity in outer mature enamel (p<0.01) and an increase in the calcium/phosphorus ratio in that structure (p<0.05). Pamidronate did not induce ultra-structural alterations in mature enamel as revealed by SEM and did not cause a reduction in its microhardness (p>0.05). The present study indicates that pamidronate can affect birefringence of the secretory-stage EOECM, which does not seem to be associated with significant changes in morphological and/or mechanical properties of mature enamel.
Cognitive deficits are present from the onset of psychosis and are considered a core feature of the disorder. Increasing evidence suggests that cognitive function is associated with inflammatory processes. This study evaluated the association between cognition and inflammatory biomarkers in first-episode psychosis (FEP), in order to identify cognitive phenotypes from inflammatory expression profiles.
A case-control study of 92 FEP patients and 80 matched controls was used. Neurocognitive assessment, including verbal ability, sustained attention, verbal memory, working memory and executive function, was performed. The expression of pro- and anti-inflammatory mediators of the main intracellular inflammatory pathway was measured in peripheral blood mononuclear cells and plasma.
FEP patients performed worse in all cognitive domains compared to controls and had higher expression of pro-inflammatory mediators and lower expression of anti-inflammatory mediators. In the FEP group, cognition and psychopathology were associated with inflammation. Hierarchical regression analysis showed that association between the anti-inflammatory prostaglandin 15d-PGJ2 and sustained attention on one hand, and COX-2 expression and executive function on the other, were statistically significant.
Our study provides evidence for an association between anti-inflammatory biomarkers and cognition in FEP. The identification of a subgroup of patients based on these measures could be useful to guide treatment programmes by providing tools to select a personalized treatment approach, but longitudinal studies are needed before. In the future, establishment of biomarkers linked to cognition would be useful to monitor the course of cognitive impairment, but substantially more data will be required. Determination of IκBα, the inhibitory protein of the pro-inflammatory transcription factor NFκB, could be useful in early phases to assess clinical severity.
N-3 polyunsaturated fatty acids (PUFAs) have been hypothesised to be protective for depression during pregnancy. However, there are few data and no consensus regarding this association. In this line, we aim to evaluate if the concentration of n-3 and n-6 PUFAs, and their ratio, are associated with depressive symptoms throughout pregnancy.
A prospective cohort of 172 Brazilian women was followed at 5–13th, 20–26th and 30–36th weeks of gestation. The presence of depressive symptoms was evaluated using the Edinburgh Postnatal Depression Scale (EPDS) at each pregnancy trimester. Depression was defined as an EPDS score ≥11. The concentrations of n-3 [α-linolenic acid; eicosapentaenoic acid (EPA); docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA)] and n-6 PUFAs [linoleic acid; γ linolenic acid; eicosadienoic acid; eicosatrienoic acid; arachidonic acid; docosatetraenoic acid and docosapentaenoic acid] were expressed as absolute (μg/ml) values. The total n-6/n-3 ratio was calculated. Statistical analyses were performed using univariate and adjusted random intercept logistic model for each fatty acid (FA) considering the longitudinal nature of data. Covariates were selected as potential confounders based on their biological plausibility of having an association with the concentration of FA and depressive symptoms during pregnancy.
The prevalence of depressive symptoms was high in all pregnancy trimesters (1st = 33.7%; 2nd = 18.9%; 3rd = 17.4%). We did not find differences in means FA concentrations by depressive symptom classification, for each follow-up visit. The women presented a 5% decrease in the odds of having depressive symptoms for each one-week increase in the gestational age. As individual women progressed through pregnancy, higher concentrations of EPA (odds ratio (OR) = 0.92; 95% CI: 0.86–0.99), DHA (OR = 0.96; 95% CI: 0.93–0.99), DPA (OR = 0.87; 95% CI: 0.77–0.99) and total n-3 (OR = 0.98; 95% CI: 0.96–0.99) were associated with a lower odds of depressive symptoms, while higher total n-6/n-3 ratio were associated with greater odds of depressive symptoms (OR = 1.40; 95% CI: 1.09–1.79). We detected a decrease in the probability of depressive symptoms as concentrations of total n-3 FA, α-linolenic acid, DPA, and DHA increased. We also observed a sharper decline for women with initial greater chance of depressive symptoms compared with those with lower chance of having these symptoms.
We found a high prevalence of depressive symptoms in low-income Brazilian pregnant women and no significant associations between n-6 FA and depressive symptoms. Lower serum concentrations of DHA, EPA and DPA and a higher n-6/n-3 ratio at each pregnancy trimester were associated with higher odds of depressive symptoms throughout pregnancy.
The influence of genotype (lean v. fatty) and dietary protein level (normal v. reduced) on plasma metabolites, hepatic fatty acid composition and mRNA levels of lipid-sensitive factors is reported for the first time, using the pig as an experimental model. The experiment was conducted on forty entire male pigs (twenty lean pigs of Large White×Landrace×Pietrain cross-breed and twenty fatty pigs of Alentejana purebreed) from 60 to 93 kg of live weight. Each pig genotype was divided into two subgroups, which were fed the following diets: a normal protein diet (NPD) equilibrated for lysine (17·5 % crude protein and 0·7 % lysine) and a reduced protein diet (RPD) not equilibrated for lysine (13·1 % crude protein and 0·4 % lysine). The majority of plasma metabolites were affected by genotype, with lean pigs having higher contents of lipids, whereas fatty pigs presented higher insulin, leptin and urea levels. RPD increased plasma TAG, free fatty acids and VLDL-cholesterol compared with NPD. Hepatic total lipids were higher in fatty pigs than in the lean genotype. RPD affected hepatic fatty acid composition but had a slight influence on gene expression levels in the liver. Sterol regulatory element-binding factor 1 was down-regulated by RPD, and fatty acid desaturase 1 (FADS1) and fatty acid binding protein 4 (FABP4) were affected by the interaction between genotype and diet. In pigs fed RPD, FADS1 was up-regulated in the lean genotype, whereas FABP4 increased in the fatty genotype. Although there is a genotype-specific effect of dietary protein restriction on hepatic lipid metabolism, lipogenesis is not promoted in the liver of lean or fatty pigs.
Human toxocarosis is a chronic tissue parasitosis most often caused by Toxocara canis. The seroprevalence can reach up to 50%, especially among children and adolescents. The anthelmintics used in the treatment have moderate efficacy. The aim of this study was to evaluate the in vitro and in vivo anthelmintic activity of quinones and their derivatives against T. canis larvae and the cytotoxicity of the larvicidal compounds. The compounds were evaluated at 1 mg mL−1 concentration in microculture plates containing third stage larvae in an Roswell Park Memorial Institute (RPMI) 1640 environment, incubated at 37 °C in 5% CO2 tension for 48 h. Five naphthoxiranes were selected for the cytotoxicity analysis. The cell viability evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays using murine peritoneal macrophages isolated from C57BL/6 mice revealed that the naphthoxiranes (1 and 3) were less cytotoxic at a concentration of 0·05 mg mL−1. The efficacy of naphthoxiranes (1 and 3) was examined in murine toxocarosis also. The anthelmintic activity was examined by evaluating the number of larvae in the brain, carcass, liver, lungs, heart, kidneys and eyes. Compound (3) demonstrated anthelmintic activity similar to that of albendazole by decreasing the number of larvae in the organs of mice and thus could form the basis of the development of a new anthelmintic drug.
Few randomised clinical trials have examined the efficacy of an
intervention aimed at improving psychosocial functioning in bipolar
To examine changes in psychosocial functioning in a group that has been
enrolled in a functional remediation programme 1 year after baseline.
This was a multicentre, randomised, rater-masked clinical trial comparing
three patient groups: functional remediation, psychoeducation and
treatment as usual over 1-year follow-up. The primary outcome was change
in psychosocial functioning measured by means of the Functioning
Assessment Short Test (FAST). Group×time effects for overall psychosocial
functioning were examined using repeated-measures ANOVA (trial
There was a significant group×time interaction for overall psychosocial
functioning, favouring patients in the functional remediation group
(F = 3.071, d.f. = 2, P =
Improvement in psychosocial functioning is maintained after 1-year
follow-up in patients with bipolar disorder receiving functional
Functional remediation is a novel intervention with demonstrated efficacy at improving functional outcome in euthymic bipolar patients. However, in a previous trial no significant changes in neurocognitive measures were detected. The objective of the present analysis was to test the efficacy of this therapy in the enhancement of neuropsychological functions in a subgroup of neurocognitively impaired bipolar patients.
A total of 188 out of 239 DSM-IV euthymic bipolar patients performing below two standard deviations from the mean of normative data in any neurocognitive test were included in this subanalysis. Repeated-measures analyses of variance were conducted to assess the impact of the treatment arms [functional remediation, psychoeducation, or treatment as usual (TAU)] on participants’ neurocognitive and functional outcomes in the subgroup of neurocognitively impaired patients.
Patients receiving functional remediation (n = 56) showed an improvement on delayed free recall when compared with the TAU (n = 63) and psychoeducation (n = 69) groups as shown by the group × time interaction at 6-month follow-up [F2,158 = 3.37, degrees of freedom (df) = 2, p = 0.037]. However, Tukey post-hoc analyses revealed that functional remediation was only superior when compared with TAU (p = 0.04), but not with psychoeducation (p = 0.10). Finally, the patients in the functional remediation group also benefited from the treatment in terms of functional outcome (F2,158 = 4.26, df = 2, p = 0.016).
Functional remediation is effective at improving verbal memory and psychosocial functioning in a sample of neurocognitively impaired bipolar patients at 6-month follow-up. Neurocognitive enhancement may be one of the active ingredients of this novel intervention, and, specifically, verbal memory appears to be the most sensitive function that improves with functional remediation.