Zika virus (ZIKV) is associated with brain development abnormalities such as primary microcephaly, a severe reduction in brain growth. Here we demonstrated in vivo the impact of congenital ZIKV ...infection in blood vessel development, a crucial step in organogenesis. ZIKV was injected intravenously in the pregnant type 2 interferon (IFN)-deficient mouse at embryonic day (E) 12.5. The embryos were collected at E15.5 and postnatal day (P)2. Immunohistochemistry for cortical progenitors and neuronal markers at E15.5 showed the reduction of both populations as a result of ZIKV infection. Using confocal 3D imaging, we found that ZIKV infected brain sections displayed a reduction in the vasculature density and vessel branching compared to mocks at E15.5; altogether, cortical vessels presented a comparatively immature pattern in the infected tissue. These impaired vascular patterns were also apparent in the placenta and retina. Moreover, proteomic analysis has shown that angiogenesis proteins are deregulated in the infected brains compared to controls. At P2, the cortical size and brain weight were reduced in comparison to mock-infected animals. In sum, our results indicate that ZIKV impairs angiogenesis in addition to neurogenesis during development. The vasculature defects represent a limitation for general brain growth but also could regulate neurogenesis directly.
The present work introduces hydro-wind correlation maps of Brazil calculated with wind speed data from weather stations and the registered historical natural inflows. The building of hydro-wind ...correlation maps was based on Voronoi cells, associated with values of correlation coefficients between seasonally averaged wind speeds and stream flows. We carried out four different correlation analyses. From the computed hydrologic correlation, we determined the most representative hydropower plants for each Brazilian basin. The wind correlation analysis confirmed the high similarity of the wind regimes throughout the country, but showed that the space variability is higher than the time variability. Local hydro-wind correlation analysis refers to the correlation between a basin's representative stream flow and the weather stations inside the same basin. The non-local analysis involved the correlation for each different stream flow regime with wind speed data from all the weather stations. Hydro-wind correlation maps are quantitative and more intuitive than previous analyses of wind and hydropower complementarity. By their use, it is possible to discern different behaviors for hydro-wind correlation throughout the Brazilian territory, either confirming previous results or identifying new features. Two examples show that hydro-wind correlation maps can be useful for operation and the expansion strategies.
•We introduce correlation maps as a tool for hydro-wind complementarity analysis.•We built hydro-wind correlation maps with historical data over a Voronoi diagram.•We used stream flow and wind speed data extending throughout Brazilian territory.•Basins and stations near São Francisco River show the highest local complementarity.•Amazon River and wind of NE and S regions show the best non-local complementarity.
In bananas, the major carotenoids are α- and β-carotene, which give this fruit great potential in biofortification programs. The carotenoid content in pulp and peel of 22 banana and plantain ...genotypes was determined in order to evaluate the impact of ripening on the carotenoid content as well as its retention after different thermal processes. Fruits were ripened at stage 2 (green), 5 (yellow) and 7 (yellow with dark spots). The provitamin A content (pVACs) varied from 20.8 (‘Muisa Tia’ stg 7) to 6341.5 μg/100 g f.w. (‘Samurá B’ stg 5). High quantities were identified in plantains, which have yellow pulp, a phenotypic characteristic that can indicate the quantity of pVACs in Musa spp. fruit. The ‘Samurá B’ plantain showed the highest pVACs (6341.5 μg/100 g f.w.) and trans-β-carotene (5220.0 μg/100 g f.w.) content in pulp, especially when compared to the ‘D'Angola’ plantain (pVACs: 3214.0 μg/100 g f.w.), the most common in Brazil, and with the dessert cultivar from the Cavendish subgroup (‘Grand Naine’ – pVACs: 230.6 μg/100 g f.w.), the most consumed worldwide. The highest pVACs quantity was verified in the ripe fruit (stg 5), decreasing during the fruit ripening (stg 7). In the peels, lutein was the majority compost, with contents higher than the pulp. The highest lutein content was identified in the green fruit peels from the ‘Terra Anã Branca’ cultivar (1602.1 μg/100 g d.w.), almost ten times higher than the content found in the pulp of the same cultivar. However, the pulp of all the cultivars showed superior values of pVACs, trans-β-carotene and trans-α-carotene, mainly in the ripe stage 5. The plantain ‘Samurá B’ has nutritional and/or functional properties, and its promotion/incorporation in existing agricultural systems is of interest for use in biofortification programs. In addition, thermal processing can improve bioactive compounds release and increase the functional and nutritional value of the Musa spp. fruit, mainly by boiling, which should be the favorite in domestic preparations, regardless of the cultivar used.
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•Twenty-two banana and plantain genotypes were analyzed.•Bananas and plantains contain as major carotenoid α and β-carotene.•Highest lutein content was found in the green fruit peel.•High levels of pro-vitamin A carotenoids occur in plantain with yellow pulp.•Boiling process improve the pro-vitamin A carotenoids release in Musa spp. fruits.
Aims
CONCERT‐HF is an NHLBI‐sponsored, double‐blind, placebo‐controlled, Phase II trial designed to determine whether treatment with autologous bone marrow‐derived mesenchymal stromal cells (MSCs) ...and c‐kit positive cardiac cells (CPCs), given alone or in combination, is feasible, safe, and beneficial in patients with heart failure (HF) caused by ischaemic cardiomyopathy.
Methods and results
Patients were randomized (1:1:1:1) to transendocardial injection of MSCs combined with CPCs, MSCs alone, CPCs alone, or placebo, and followed for 12 months. Seven centres enrolled 125 participants with left ventricular ejection fraction of 28.6 ± 6.1% and scar size 19.4 ± 5.8%, in New York Heart Association class II or III. The proportion of major adverse cardiac events (MACE) was significantly decreased by CPCs alone (−22% vs. placebo, P = 0.043). Quality of life (Minnesota Living with Heart Failure Questionnaire score) was significantly improved by MSCs alone (P = 0.050) and MSCs + CPCs (P = 0.023) vs. placebo. Left ventricular ejection fraction, left ventricular volumes, scar size, 6‐min walking distance, and peak oxygen consumption did not differ significantly among groups.
Conclusions
This is the first multicentre trial assessing CPCs and a combination of two cell types from different tissues in HF patients. The results show that treatment is safe and feasible. Even with maximal guideline‐directed therapy, both CPCs and MSCs were associated with improved clinical outcomes (MACE and quality of life, respectively) in ischaemic HF without affecting left ventricular function or structure, suggesting possible systemic or paracrine cellular mechanisms. Combining MSCs with CPCs was associated with improvement in both these outcomes. These results suggest potential important beneficial effects of CPCs and MSCs and support further investigation in HF patients.
Cardiovascular Cell Therapy Research Network: the CONCERT‐HF trial. CONCERT‐HF is the first multicentre trial assessing c‐kit positive cardiac cells (CPCs) and a combination of two cell types from different tissues in heart failure (HF) patients. Administration of autologous CPCs or mesenchymal stromal cells (MSCs) in patients with chronic ischaemic HF shows promising effects, namely, a reduction in hospitalization for HF and an improvement in quality of life, respectively, over the ensuing 12 months. Results of this Phase II study provide a rationale for additional clinical trials of cell therapy in chronic ischaemic HF.
Previous meta-analyses have linked social connections and mild cognitive impairment, dementia, and mortality. However, these used aggregate data from North America and Europe and examined a limited ...number of social connection markers.
We used individual participant data (N = 39271, M
= 70.67 (40-102), 58.86% female, M
= 8.43 years, M
= 3.22 years) from 13 longitudinal ageing studies. A two-stage meta-analysis of Cox regression models examined the association between social connection markers with our primary outcomes.
We found associations between good social connections structure and quality and lower risk of incident mild cognitive impairment (MCI); between social structure and function and lower risk of incident dementia and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality.
Different aspects of social connections - structure, function, and quality - are associated with benefits for healthy aging internationally.
Social connection structure (being married/in a relationship, weekly community group engagement, weekly family/friend interactions) and quality (never lonely) were associated with lower risk of incident MCI. Social connection structure (monthly/weekly friend/family interactions) and function (having a confidante) were associated with lower risk of incident dementia. Social connection structure (living with others, yearly/monthly/weekly community group engagement) and function (having a confidante) were associated with lower risk of mortality. Evidence from 13 longitudinal cohort studies of ageing indicates that social connections are important targets for reducing risk of incident MCI, incident dementia, and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality.
Statin therapy reduces adverse outcomes, with a minimal decrease in vessel stenosis. Magnetic resonance imaging (MRI) noninvasively detects atherosclerotic plaque (AP) reduction. We hypothesized that ...statin-induced AP regression can be monitored by MRI and detected earlier than previously reported and is significantly associated with its lipid-lowering effect.
APs in thoracic aorta were measured by combined surface/transesophageal MRI in 27 patients (treated with simvastatin 20 to 80 mg daily) before and after 6 months of therapy. AP volume and luminal dimensions were measured from 6 cross sections used to construct a 2.4-cm 3D volume of the aorta that included plaque and lumen. Method reproducibility was studied in 10 patients imaged twice, 1 week apart. AP volume was reduced from 3.3+/-0.1.4 to 2.9+/-1.4 cm3 at 6 months (P<0.02), whereas luminal volume increase was less accentuated (from 12.0+/-3.9 to 12.2+/-3.7 cm3, P<0.06). LDL cholesterol decreased by 23% (from 125+/-32 to 97+/-27 mg/dL, P<0.05) in 6 months. AP regression (plaque volume/area reduction) was significantly related to LDL cholesterol reduction (P<0.02 and P<0.005, respectively), and luminal volume increase was inversely related to LDL cholesterol reduction (P<0.04). Plaque volume measurement was highly reproducible (intraclass correlation R=0.98 and variability=4.8%). Intraobserver (0.91) and interobserver (0.81) concordances were documented for plaque volume assessment.
AP regression and reverse remodeling can be detected accurately by MRI 6 months after statin therapy initiation, and it is strongly associated with LDL cholesterol reduction.
Land cover in sub-polar and alpine regions of northern and eastern
Europe have already begun changing due to natural and anthropogenic changes
such as afforestation. This will impact the regional ...climate and hydrology
upon which societies in these regions are highly reliant. This study aims to
identify the impacts of afforestation/reforestation (hereafter
afforestation) on snow and the snow-albedo effect and highlight potential
improvements for future model development. The study uses an ensemble of
nine regional climate models for two different idealised experiments
covering a 30-year period; one experiment replaces most land cover in Europe
with forest, while the other experiment replaces all forested areas with
grass. The ensemble consists of nine regional climate models composed of
different combinations of five regional atmospheric models and six land
surface models. Results show that afforestation reduces the snow-albedo
sensitivity index and enhances snowmelt. While the direction of change is
robustly modelled, there is still uncertainty in the magnitude of change.
The greatest differences between models emerge in the snowmelt season. One
regional climate model uses different land surface models which shows
consistent changes between the three simulations during the accumulation
period but differs in the snowmelt season. Together these results point to
the need for further model development in representing both grass–snow and
forest–snow interactions during the snowmelt season. Pathways to
accomplishing this include (1) a more sophisticated representation of forest
structure, (2) kilometre-scale simulations, and (3) more observational studies
on vegetation–snow interactions in northern Europe.
Because of its usefulness in treating facial rosacea, metronidazole may also be an effective treatment for ocular rosacea. The toxicity of metronidazole on the corneal epithelium has not previously ...been reported. In this study, the effects of metronidazole on rabbit corneal epithelium in vitro were evaluated. Epithelial cell cultures were exposed to various concentrations of metronidazole to determine its effect on cell morphology, viability, and wound healing. Both morphological changes and cell loss were seen after 1 day of incubation in media containing metronidazole at concentrations of > or = 3.0 mg/ml. In media with metronidazole at 1.0 mg/ml, these toxic effects were not seen. The effects of metronidazole on wound healing were determined by comparing the area of wounds in the epithelial cell layer for time periods of up to 44 h. There was no statistically significant delay in wound closure when cells were incubated in media containing metronidazole at a concentration of 2.0 mg/ml as compared with cultures incubated in media without metronidazole. However, a significant delay in wound closure occurred at concentrations of > or = 3.0 mg/ml. The results at these drug concentrations suggest that metronidazole has low corneal epithelial toxicity. Allowing for the dilutional effects of tears in patients with normal tear function, concentrations of 4.0-5.0 mg/ml (0.4-0.5%) would probably be tolerated by the corneal epithelium. Clinical safety and efficacy studies are necessary to determine if topical metronidazole will prove useful for the treatment of ocular rosacea.
Background N-terminal-pro–B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (TnT) predict cardiovascular disease (CVD) risk in a variety of populations. Whether their predictive value ...varies by ethnicity is unknown. We sought to determine whether NT-proBNP and TnT improve prediction of incident coronary heart disease (CHD) and CVD, independent of CVD risk factors, in a multiethnic population; whether NT-proBNP improves prediction compared with the Framingham Risk Score or the Pooled Cohort Risk Equation; and whether a second NT-proBNP further improves prediction. Methods Both NT-proBNP and TnT were measured in 5,592 MESA white, black, Hispanic, and Chinese participants (60% nonwhite; mean age 62.3 ± 10.3 years) in 2000 to 2002 and 2004 to 2005. We evaluated adjusted risk of incident CHD and CVD based on baseline and change in biomarker concentration. Results Participants were followed up through 2011 and incurred 370 CVD events (232 CHD). Concentrations of NT-proBNP and TnT varied by ethnicity. Both NT-proBNP and TnT were associated with an increased risk of events (adjusted hazard ratio HR for CHD 95% CI for fifth quintile vs other 4 quintiles of NT-proBNP, 2.03 1.50-2.76; HR for CHD for detectable vs undetectable TnT, 3.95 2.29-6.81). N-terminal-pro–B-type natriuretic peptide improved risk prediction and classification compared with the Framingham Risk Score and the Pooled Cohort Risk Equation. Change in NT-proBNP was independently associated with events (HR for CHD per unit increase in ΔlogNT-proBNP, 1.95 1.16-3.26). None of the observed associations varied by ethnicity. Conclusions Both NT-proBNP and TnT are predictors of incident CHD, independent of established risk factors and ethnicity, in a multiethnic population without known CVD. Change in NT-proBNP may add additional prognostic information.
•CeO2100-x-S8x nanohybrids are prepared by a simple and rapid synthetic approach.•The CeO270-S830 nanohybrid presents a capacity of 600 mA h g–1 over 160 cycles.•CeO270-S830 promotes fast redox ...reactions, making the shuttle effect negligible.•DFT results reveal strong interactions between the CeO2 surface and sulfur species.
An in-depth investigation of the physical and chemical parameters that affect Li-sulfur batteries is imperative to optimize their performances. Here, we report promising CeO2100-x-S8x nanohybrids for anchoring lithium polysulfides (LiPSs) that are generated during cycling. The composition of CeO2100- x-S8x (x = 30, 50 and 70%) could be simply controlled by varying the CeO2/S8 mass ratio added in each reaction. Our results indicated that the CeO2100- x-S8x nanohybrids displayed a crystalline structure composed of both phases (CeO2 and S8), indicating an efficient impregnation process of S8 on the CeO2 nanowire surface. The surface area of CeO2 nanowires decreased as the amount of S8 was increased, and the CeO270-S830 nanohybrid maintained a uniform distribution of S8 over the entire CeO2 nanowires. Remarkably, the CeO270-S830 nanohybrid showed the best Li-storage performance, leading to specific capacities of approximately 600 mA h g–1 over 160 cycles and a Coulombic efficiency of approximately 100%. Moreover, this sample showed excellent rate capability performance (even discharging at 10 A g–1). Additionally, the chemical interaction of CeO2 with LiPS was demonstrated by a visual experiment through the addition of pure CeO2 in a solution of Li2S6. The solution containing CeO2 nanowires became completely colorless after 30 min. To further investigate these improvements, density functional theory (DFT) calculations revealed the formation of strong interactions between the CeO2 nanowire surface and different sulfur species. For instance, the adsorption energies between the CeO2 nanowires and S8, Li2S4, and Li4S8 were –3.95, –5.84 and –7.31 eV, respectively, suggesting that the CeO270-S830 nanohybrid provided an appropriate surface to anchor LiPS by electrostatic interactions, leading to faster redox kinetics in Li-sulfur battery applications.
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