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The population dynamics of shrimp Pleoticus muelleri was used as a model to verify if the trend of continuous reproduction periodicity, shorter body size and longevity, and early sexual maturity found in tropical regions is corroborated in upwelling regions. Shrimps were sampled in a region under the influence of upwelling (northern coast of Rio de Janeiro State, Brazil). Characteristics of bottom water were registered, and shrimps were measured (carapace length – CL) and classified by sex and gonadal development stages. Reproduction was seasonal, from September to December, and favoured by water mass intrusions of low temperatures and high chlorophyll concentrations. The greatest number of reproductive females preceded periods with the highest chlorophyll concentrations in the water column (cross-correlation; P < 0.05, lag (month) = −3, r = 0.50), suggesting greater developmental success of larval stage due to increase of food availability. Von Bertalanffy growth models resulted in asymptotic carapace length estimates of CL∞ = 40.21 mm and CL∞ = 36.78 mm for females and males, respectively. The reproductive and growth characteristics of the P. muelleri population studied herein were similar to that of populations from higher latitudes, demonstrating that the latitudinal pattern rule cannot be applied in regions influenced by an upwelling phenomenon.
Chagas disease (CD) is a neglected parasitic condition endemic in the Americas caused by Trypanosoma cruzi. Patients present an acute phase that may or not be symptomatic, followed by lifelong chronic stage, mostly indeterminate, or with cardiac and/or digestive progressive lesions. Benznidazole (BZ) and nifurtimox are the only drugs approved for treatment but not effective in the late chronic phase and many strains of the parasite are naturally resistant. New alternative therapy is required to address this serious public health issue. Repositioning and combination represent faster, and cheaper trial strategies encouraged for neglected diseases. The effect of imatinib (IMB), a tyrosine kinase inhibitor designed for use in neoplasias, was assessed in vitro on T. cruzi and mammalian host cells. In comparison with BZ, IMB was moderately active against different strains and forms of the parasite. The combination IMB + BZ in fixed-ratio proportions was additive. Novel 14 derivatives of IMB were screened and a 3,2-difluoro-2-phenylacetamide (3e) was as potent as BZ on T. cruzi but had low selectivity index. The results demonstrate the importance of phenotypic assays, encourage the improvement of IMB derivatives to reach selectivity and testify to the use of repurposing and combination in drug screening for CD.
Hepatocytes constitute the majority of hepatic cells, and play a key role in controlling systemic innate immunity, via pattern-recognition receptors (PRRs) and by synthesizing complement and acute phase proteins. Leishmania infantum, a protozoan parasite that causes human and canine leishmaniasis, infects liver by establishing inside the Kupffer cells. The current study proposes the elucidation of the immune response generated by dog hepatocytes when exposed to L. infantum. Additionally, the impact of adding leishmanicidal compound, meglumine antimoniate (MgA), to parasite-exposed hepatocytes was also addressed. L. infantum presents a high tropism to hepatocytes, establishing strong membrane interactions. The possibility of L. infantum internalization by hepatocytes was raised, but not confirmed. Hepatocytes were able to recognize parasite presence, inducing PRRs [nucleotide oligomerization domain (NOD)1, NOD2 and Toll-like receptor (TLR)2] gene expression and generating a mix pro- and anti-inflammatory cytokine response. Reduction of cytochrome P 450s enzyme activity was also observed concomitant with the inflammatory response. Addition of MgA increased NOD2, TLR4 and interleukin 10 gene expression, indicating an immunomodulatory role for MgA. Hepatocytes seem to have a major role in coordinating liver's innate immune response against L. infantum infection, activating inflammatory mechanisms, but always balancing the inflammatory response in order to avoid cell damage.
Monosodium l-glutamate (MSG)-induced obesity is a useful model for non-alcoholic fatty liver disease (NAFLD) studies. However, there is limited data on its initiation and progression. Thus, this study aimed to characterize the onset of metabolic and histopathological features of NAFLD and its progression to non-alcoholic steatohepatitis (NASH) in this model. To perform this study, Swiss mice pups were neonatally injected with MSG (4 g/kg/day, s.c.) or equiosmolar saline and followed up to 60, 120 or 180 days old. At each age, blood, liver, as well as periepididymal and retroperitoneal fat pads were collected for morphometric, biochemical and histological analyses, the later according to NAFLD activity score. MSG mice presented hypertriglyceridemia and central obesity at all ages, but peripheral insulin-resistance was verified only in 120- and 180-day-old mice. Hepatic total fat and triglycerides content were higher in MSG mice at all ages. Accordingly, histopathological analysis showed that 60-day-old MSG mice had microvesicular steatosis with occasional ballooning, which evolved into NASH from 120 days old. Retroperitoneal fat accumulation was the only variable to independently correlate with NAFLD activity total score upon multivariate analysis (R2=71.45%). There were no differences in IL-6 and TNF-α serum levels among groups. Overall, this study shows that NAFLD is a precocious outcome in MSG-obese mice, whereas the period comprised between 60 and 120 days old seems to be a crucial metabolic window for comprehending pathophysiological events involved in NAFLD-to-NASH progression in this model.
We studied the ontogenetic growth of goat wethers (castrated male goats) of the Saanen and Swiss Alpine breeds based on a large range of intraspecific body mass (BM). The body parts and the chemical constituents of the empty body were described by the allometric function by using BM and the empty body mass (EBM) as the predictors for morphological traits and chemical composition, respectively. We fitted the allometric scaling function by applying the SAS NLMIXED procedure, but to evaluate assumptions regarding variances in morphological and compositional traits, we combined the scaling function with homoscedastic (MOD1), and the heteroscedastic exponential (MOD2) and power-of-the-mean (MOD3) variance functions. We also predicted the ontogenetic growth by using the traditional log-log transformation and back-transformed results into the arithmetic scale (MOD4). We obtained predictions from MOD4 in the arithmetic scale by a two-step process, and evaluated MOD1, MOD2 and MOD3 by a model selection framework, and compared MOD4 with MOD1, MOD2 and MOD3 based on goodness-of-fit measures. Based on information criteria for model selection, heterogeneous variance functions were more likely to describe 10 over 36 traits with a low level of model selection uncertainty. One trait was predicted by averaging the MOD1 and MOD2 variance functions; and nine traits were better described by averaging the MOD2 and MOD3 variance functions. The predictions for other 16 traits were averaged from MOD1, MOD2 and MOD3. However, MOD4 better described 11 traits according to the goodness-of-fit measures. Depending on the variable being analyzed, the body parts and the chemical amounts exhibited the three types of allometric behavior with respect to BM and EBM, that is, positive, negative and isometric ontogenetic growth. Reference BMs, that is, 20, 27, 35 and 45 kg, were used to compute the net protein and energy requirements based on the first derivative of the scaling function, and the results were presented in reference to the EBM and EBM0.75. Both the net protein and energy requirements scaled to EBM0.75 increased from 20 to 45 kg of BM.
The control of dengue constitutes a great challenge for public health; however, the methods normally used have shown themselves to be insufficient to keep the indices of infestation of Aedes aegypti under control. Recently, beyond the large number of cases and deaths associated with dengue, new risks have arisen such as those represented by chikungunya fever and Zika. In the light of the great significance of these problems within the public health context, two areas in a municipality in the interior of the State of São Paulo, Brazil were selected in 2014. One of them, Bairro Cidade Nova, was submitted to the conventional method of nebulization with portable equipment, and the other, Bairro Jardim Europa, received the application of the insecticide by means of heavy-equipment coupled to the vehicle. During the project, 1355 mosquito eggs were collected, 1105 of them in Bairro Cidade Nova and 205 in Bairro Jardim Europa. After the applications with heavy-equipment in the months of March and April, the number of cases of the disease reported in the month of April for Bairro Jardim Europa was less than half that of Bairro Cidade Nova, which had received the conventional treatment. The nebulization with the heavy-equipment may constitute a viable and effective strategy for achieving better results in the control of Ae. aegypti.
The classical Ross–Macdonald model is often utilized to model vector-borne infections; however, this model fails on several fronts. First, using measured (or estimated) parameters, which values are accepted from the literature, the model predicts a much greater number of cases than what is usually observed. Second, the model predicts a single large outbreak that is followed by decades of much smaller outbreaks, which is not consistent with what is observed. Usually towns or cities report a number of recurrences for many years, even when environmental changes cannot explain the disappearance of the infection between the peaks. In this paper, we continue to examine the pitfalls in modelling this class of infections, and explain that, if properly used, the Ross–Macdonald model works and can be used to understand the patterns of epidemics and even, to some extent, be used to make predictions. We model several outbreaks of dengue fever and show that the variable pattern of yearly recurrence (or its absence) can be understood and explained by a simple Ross–Macdonald model modified to take into account human movement across a range of neighbourhoods within a city. In addition, we analyse the effect of seasonal variations in the parameters that determine the number, longevity and biting behaviour of mosquitoes. Based on the size of the first outbreak, we show that it is possible to estimate the proportion of the remaining susceptible individuals and to predict the likelihood and magnitude of the eventual subsequent outbreaks. This approach is described based on actual dengue outbreaks with different recurrence patterns from some Brazilian regions.
The precocious interruption of lactation is a prime factor for developmental plasticity. Here we analyzed whether flour or flaxseed oil treatment contributes to body and brain mass in male rats subjected to early weaning. Pups were weaned for separation from their mother at 14 (early weaning, EW) and 21 days (control, C). At 21 days, some of the pups were evaluated (C21 v. EW21). After 21 days, control pups (C60) were fed a control diet. EW pups were divided into those fed a control diet (EWC60), those given flaxseed flour (EWFF60), and those given flaxseed oil (EWFO60) until 60 days. EW21 showed lower body and absolute brain mass and higher relative brain mass. At 60 days, EWC60 and EWFO60 had lower body mass. With regard to relative brain mass, EWC60 was heavier; EWFO60 had lower values compared with EWC60 and higher values compared with C60 and EWFF60. These results indicated that flaxseed flour, in comparison with flaxseed oil, contributes to brain development after EW.
Objectives: The Carpentier-Edwards pericardial (CEP) prostheses are the type of bioprostheses most used worldwide. Although they were designed to minimize the rate of valve deterioration and reoperation, their clinical superiority over other prostheses models still lacks confirmation. The objective of this study was to evaluate its effectiveness.
Methods: We performed a systematic review and meta-analysis in the PubMed, Embase, Cochrane, and Lilacs databases. Operative mortality, overall mortality and reoperation rates after heart valve surgery were compared between the use of CEP and other cardiac prostheses. Two independent reviewers screened studies for inclusion and extracted the data. Disagreements were resolved by consensus. The GRADE criterion was used to assess the evidence quality.
Results: A total of twenty-eight studies were selected, including 19,615 individuals. The studies presented a high heterogeneity and low quality of evidence what limited the reliability of the results. The pooled data from the selected studies did not demonstrate significant differences between CEP and porcine, pericardial or stentless prostheses regarding operative mortality, overall mortality and reoperation rates. However, the pooled data from 3 observational trials pointed out a higher risk for reoperation after valve replacement using CEP prostheses against mechanical prostheses (OR 4.92 [95 percent confidence interval 2.43–9.96]).
Conclusions: The current data present in the literature still does not support a clinical advantage for the use of CEP prostheses over other bioprostheses. The quality of the studies in the literature is limited and further studies are needed to address if CEP prostheses will have a clinical advantage over other prostheses.
Different dietary interventions have been identified as potential modifiers of adiponectin concentrations, and they may be influenced by lipid intake. We identified studies investigating the effect of dietary lipids (type/amount) on adiponectin concentrations in a systematic review with meta-analysis. A literature search was conducted until July 2013 using databases such as Medline, Embase and Scopus (MeSH terms: ‘adiponectin’, ‘dietary lipid’, ‘randomized controlled trials (RCT)’). Inclusion criteria were RCT in adults analysing adiponectin concentrations with modification of dietary lipids. Among the 4930 studies retrieved, fifty-three fulfilled the inclusion criteria and were grouped as follows: (1) total dietary lipid intake; (2) dietary/supplementary n-3 PUFA; (3) conjugated linoleic acid (CLA) supplementation; (4) other dietary lipid interventions. Diets with a low fat content in comparison to diets with a high-fat content were not associated with positive changes in adiponectin concentrations (twelve studies; pooled estimate of the difference in means: − 0·04 (95 % CI − 0·82, 0·74) μg/ml). A modest increase in adiponectin concentrations with n-3 PUFA supplementation was observed (thirteen studies; 0·27 (95 % CI 0·07, 0·47) μg/ml). Publication bias was found by using Egger's test (P= 0·01) and funnel plot asymmetry. In contrast, CLA supplementation reduced the circulating concentrations of adiponectin compared with unsaturated fat supplementation (seven studies; − 0·74 (95 % CI − 1·38, − 0·10) μg/ml). However, important sources of heterogeneity were found as revealed by the meta-regression analyses of both n-3 PUFA and CLA supplementation. Results of new RCT would be necessary to confirm these findings.
Certain trypanosomatids co-evolve with an endosymbiotic bacterium in a mutualistic relationship that is characterized by intense metabolic exchanges. Symbionts were able to respire for up to 4 h after isolation from Angomonas deanei. FCCP (carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone) similarly increased respiration in wild-type and aposymbiotic protozoa, though a higher maximal O2 consumption capacity was observed in the symbiont-containing cells. Rotenone, a complex I inhibitor, did not affect A. deanei respiration, whereas TTFA (thenoyltrifluoroacetone), a complex II activity inhibitor, completely blocked respiration in both strains. Antimycin A and cyanide, inhibitors of complexes III and IV, respectively, abolished O2 consumption, but the aposymbiotic protozoa were more sensitive to both compounds. Oligomycin did not affect cell respiration, whereas carboxyatractyloside (CAT), an inhibitor of the ADP-ATP translocator, slightly reduced O2 consumption. In the A. deanei genome, sequences encoding most proteins of the respiratory chain are present. The symbiont genome lost part of the electron transport system (ETS), but complex I, a cytochrome d oxidase, and FoF1-ATP synthase remain. In conclusion, this work suggests that the symbiont influences the mitochondrial respiration of the host protozoan.
The aim of this study was to assess the effect of sulfamethoxazole/trimethoprim (ST) supplemented with diphenyl diselenide and sodium selenite in experimental toxoplasmosis, on oxidant/antioxidant biomarkers and cytokine levels. Eighty-four BALB/c mice were divided in seven groups: group A (negative control), and groups B to G (infected). Blood and liver samples were collected on days 4 and 20 post infection (p.i.). Levels of thiobarbituric acid (TBA) reactive substances and advanced oxidation protein products (AOPP) were assessed in liver samples. Both biomarkers were significantly increased in infected groups on day 4 p.i., while they were reduced on day 20 p.i., compared with group A. Glutathione reductase (GR) activity significantly (P<0·01) increased on day 4 p.i., in group G, compared with group A. INF-γ was significantly increased (P<0·001) in both periods, day 4 (groups B, C, F and G) and 20 p.i. (groups C, F and G). IL-10 significantly reduced (P<0·001) on day 4 p.i. in group B; however, in the same period, it was increased (P<0·001) in groups C and G, compared with group A. On day 20 p.i., IL-10 increased (P<0·001) in groups F and G. Therefore, our results highlighted that these forms of selenium, associated with the chemotherapy, were able to reduce lipid peroxidation and protein oxidation, providing a beneficial immunological balance between the production of pro- and anti-inflammatory cytokines.
Several prospective longitudinal studies have suggested that somatic/affective depressive symptoms, but not cognitive/affective depressive symptoms, are related to prognosis in patients with heart disease, but findings have been inconsistent. The aim of this study was to investigate the association of cognitive/affective and somatic/affective symptoms of depression with cardiovascular prognosis in patients with heart disease using a meta-analytic perspective.
A systematic search was performed in PubMed, EMBASE and PsycInfo. Thirteen prospective studies on symptom dimensions of depression and cardiovascular prognosis fulfilled the inclusion criteria, providing data on a total of 11 128 subjects. The risk estimates for each dimension of depressive symptoms, demographic and methodological variables were extracted from the included articles.
In least-adjusted analyses, both the somatic/affective [hazard ratio (HR) 1.30, 95% confidence interval (CI) 1.19–1.41, p < 0.001] and cognitive/affective (HR 1.07, 95% CI 1.00–1.15, p = 0.05) dimensions of depressive symptoms were associated with cardiovascular prognosis. In fully adjusted analyses, somatic/affective symptoms were significantly associated with adverse prognosis (HR 1.19, 95% CI 1.10–1.29, p < 0.001) but cognitive/affective symptoms were not (HR 1.04, 95% CI 0.97–1.12, p = 0.25). An increase of one standard deviation (±1 s.d.) in the scores of the somatic/affective dimension was associated with a 32% increased risk of adverse outcomes (HR 1.32, 95% CI 1.17–1.48, p < 0.001).
Somatic/affective depressive symptoms were more strongly and consistently associated with mortality and cardiovascular events in patients with heart disease compared with cognitive/affective symptoms. Future research should focus on the mechanisms by which somatic/affective depressive symptoms may affect cardiovascular prognosis.
The main objective of this study was to develop a polymeric drug delivery system for tamoxifen (TMX), intended to be injectable Eudragit® nanoparticles (NP) for breast cancer treatment. TMX-Eudragit-NP were characterized in terms of particle size, surface morphology, drug physical state by using photon correlation spectrometry (PCS), scanning electron microscope (SEM) and Fourier transform infrared spectroscopy (FTIR). The entrapment efficiency (%EE) and in vitro drug release studies were estimated spectrophotometrically by UV-vis technique. The cell toxicity assay was performed in 4T1 cell line using MTT test. TMX-Eudragit-NP showed a maximum entrapment efficient of 23%. The size measurements were compared with the empty nanoparticles and showed values of TMX-Eudragit-NP = 133 ± 30 nm nm, and empty- NP = 273± 50 nm. The zeta potential of particles was +65 and +38 mV for TMX-Eudragit-NP and empty-NP respectively. FTIR studies did not indicate changes in chemical structure or polymer-drug interaction. The cytotoxicity against the 4T1 cells was affected significantly by the released amount of TMX, while empty-NP exhibit no significant cytotoxicity against mouse breast cancer cells (4T1 cell line).
Obesity is characterised by chronic low-grade inflammation, and lycopene has been reported to display anti-inflammatory effects. However, it is not clear whether lycopene supplementation modulates adipokine levels in vivo in obesity. To determine whether lycopene supplementation can regulate adipokine expression in obesity, male Wistar rats were randomly assigned to receive a control diet (C, n 6) or a hyperenergetic diet (DIO, n 12) for 6 weeks. After this period, the DIO animals were randomised into two groups: DIO (n 6) and DIO supplemented with lycopene (DIO+L, n 6). The animals received maize oil (C and DIO) or lycopene (DIO+L, 10 mg/kg body weight (BW) per d) by oral administration for a 6-week period. The animals were then killed by decapitation, and blood samples and epididymal adipose tissue were collected for hormonal determination and gene expression evaluation (IL-6, monocyte chemoattractant protein-1 (MCP-1), TNF-α, leptin and resistin). There was no detectable lycopene in the plasma of the C and DIO groups. However, the mean lycopene plasma concentration was 24 nmol in the DIO+L group. Although lycopene supplementation did not affect BW or adiposity, it significantly decreased leptin, resistin and IL-6 gene expression in epididymal adipose tissue and plasma concentrations. Also, it significantly reduced the gene expression of MCP-1 in epididymal adipose tissue. Lycopene affects adipokines by reducing leptin, resistin and plasma IL-6 levels. These data suggest that lycopene may be an effective strategy in reducing inflammation in obesity.
The aim of the present study was to evaluate the Mini Nutritional Assessment (MNA), the Nutritional Risk Screening (NRS) 2002 and the American Society of Anesthesiologists Physical Status Score (ASA) as predictors of gait status and mortality 6 months after hip fracture. A total of eighty-eight consecutive patients over the age of 65 years with hip fracture admitted to an orthopaedic unit were prospectively evaluated. Within the first 72 h of admission, each patient's characteristics were recorded, and the MNA, the NRS 2002 and the ASA were performed. Gait status and mortality were evaluated 6 months after hip fracture. Of the total patients, two were excluded because of pathological fractures. The remaining eighty-six patients (aged 80·2 (sd 7·3) years) were studied. Among these patients 76·7 % were female, 69·8 % walked with or without support and 12·8 % died 6 months after the fracture. In a multivariate analysis, only the MNA was associated with gait status 6 months after hip fracture (OR 0·773, 95 % CI 0·663, 0·901; P= 0·001). In the Cox regression model, only the MNA was associated with mortality 6 months after hip fracture (hazard ratio 0·869, 95 % CI 0·757, 0·998; P= 0·04). In conclusion, the MNA best predicts gait status and mortality 6 months after hip fracture. These results suggest that the MNA should be included in the clinical stratification of patients with hip fracture to identify and treat malnutrition in order to improve the outcomes.
The present investigation of aerofoil self-noise generation and propagation concerns the effects of mean flow and quadrupole sources on the broadband noise that arises from the interaction of turbulent boundary layers with the aerofoil trailing edge and the tonal noise that arises from vortex shedding generated by laminar boundary layers and trailing-edge bluntness. Compressible large-eddy simulations (LES) are conducted for a NACA0012 aerofoil with rounded trailing edge for four flow configurations with different angles of incidence, boundary layer tripping configurations and free-stream Mach numbers. The Reynolds number based on the aerofoil chord is fixed at . The acoustic predictions are performed by the Ffowcs Williams & Hawkings (FWH) acoustic analogy formulation and incorporate convective effects. Surface and volume integrations of dipole and quadrupole source terms appearing in the FWH equation are performed using a three-dimensional wideband multi-level adaptive fast multipole method (FMM) in order to accelerate the calculations of aeroacoustic integrals. In order to validate the numerical solutions, flow simulation and acoustic prediction results are compared to experimental data available in the literature and good agreement is observed in terms of both aerodynamic and aeroacoustic results. For low-Mach-number flows, quadrupole sources can be neglected in the FWH equation and mean flow effects appear only for high frequencies. However, for higher speeds, convection effects are relevant for all frequencies and quadrupole sources have a more pronounced effect for medium and high frequencies. The convective effects are most readily observed in the upstream direction.
In this paper, the influence of the doping level at boron doped nanocrystalline diamond (BDND) films in the electrochemical determination of nitrite was reported. The morphology and the structure modifications as function of the boron doping level increase were observed. Two different doping levels were considered. A BDND film with a doping level of 30.000 ppm and one another with a doping level of 10.000 ppm was used. The columnar growth for the 30.000 ppm BDND led to a higher surface roughness and also to a greater grain size when compared to that 10.000 ppm BDND. The Raman spectra shown higher sp2-bonded carbon amount in grain boundary for the 10.000 ppm BDND film due to decrease of the grain size. The morphological and structural modifications of the BDND films were crucial for nitrite oxidation process. The 30.000 ppm BDND electrode presented a better sensitivity to the nitrite oxidation and a lower detection limit (DL) on the “as-grown” condition, while the 10.000 ppm BDND electrode presented a better analytical sensitivity and a lower DL after the surface pre-treatment with hydrogen plasma.