Summary Background In November, 2015, an epidemic of microcephaly was reported in Brazil, which was later attributed to congenital Zika virus infection. 7830 suspected cases had been reported to the ...Brazilian Ministry of Health by June 4, 2016, but little is known about their characteristics. We aimed to describe these newborn babies in terms of clinical findings, anthropometry, and survival. Methods We reviewed all 1501 liveborn infants for whom investigation by medical teams at State level had been completed as of Feb 27, 2016, and classified suspected cases into five categories based on neuroimaging and laboratory results for Zika virus and other relevant infections. Definite cases had laboratory evidence of Zika virus infection; highly probable cases presented specific neuroimaging findings, and negative laboratory results for other congenital infections; moderately probable cases had specific imaging findings but other infections could not be ruled out; somewhat probable cases had imaging findings, but these were not reported in detail by the local teams; all other newborn babies were classified as discarded cases. Head circumference by gestational age was assessed with InterGrowth standards. First week mortality and history of rash were provided by the State medical teams. Findings Between Nov 19, 2015, and Feb 27, 2015, investigations were completed for 1501 suspected cases reported to the Brazilian Ministry of Health, of whom 899 were discarded. Of the remainder 602 cases, 76 were definite, 54 highly probable, 181 moderately probable, and 291 somewhat probable of congenital Zika virus syndrome. Clinical, anthropometric, and survival differences were small among the four groups. Compared with these four groups, the 899 discarded cases had larger head circumferences (mean Z scores −1·54 vs −3·13, difference 1·58 95% CI 1·45–1·72); lower first-week mortality (14 per 1000 vs 51 per 1000; rate ratio 0·28 95% CI 0·14–0·56); and were less likely to have a history of rash during pregnancy (20·7% vs 61·4%, ratio 0·34 95% CI 0·27–0·42). Rashes in the third trimester of pregnancy were associated with brain abnormalities despite normal sized heads. One in five definite or probable cases presented head circumferences in the normal range (above −2 SD below the median of the InterGrowth standard) and for one third of definite and probable cases there was no history of a rash during pregnancy. The peak of the epidemic occurred in late November, 2015. Interpretation Zika virus congenital syndrome is a new teratogenic disease. Because many definite or probable cases present normal head circumference values and their mothers do not report having a rash, screening criteria must be revised in order to detect all affected newborn babies. Funding Brazilian Ministry of Health, Pan American Health Organization, and Wellcome Trust.
B7-H3, an immunoregulatory protein, is overexpressed in several cancers and is often associated with metastasis and poor prognosis. Here, our aim was to identify microRNAs (miRNAs) regulating B7-H3 ...and assess their potential prognostic implications in breast cancer.
MicroRNAs targeting B7-H3 were identified by transfecting two breast cancer cell lines with a library of 810 miRNA mimics and quantifying changes of B7-H3 protein levels using protein lysate microarrays. For validations we used western immunoblotting and 3'-UTR luciferase assays. Clinical significance of the miRNAs was assayed by analysing whether their expression levels correlated with outcome in two cohorts of breast cancer patients (142 and 81 patients).
We identified nearly 50 miRNAs that downregulated B7-H3 protein levels. Western immunoblotting validated the impact of the 20 most effective miRNAs. Thirteen miRNAs (miR-214, miR-363*, miR-326, miR-940, miR-29c, miR-665, miR-34b*, miR-708, miR-601, miR-124a, miR-380-5p, miR-885-3p, and miR-593) targeted B7-H3 directly by binding to its 3'-UTR region. Finally, high expression of miR-29c was associated with a significant reduced risk of dying from breast cancer in both cohorts.
We identified miRNAs efficiently downregulating B7-H3 expression. The expression of miR-29c correlated with survival in breast cancer patients, suggesting a tumour suppressive role for this miRNA.
We characterized 15 Trypanosoma cruzi isolates from bats captured in the Amazon, Central and Southeast Brazilian regions. Phylogenetic relationships among T. cruzi lineages using SSU rDNA, cytochrome ...b, and Histone H2B genes positioned all Amazonian isolates into T. cruzi I (TCI). However, bat isolates from the other regions, which had been genotyped as T. cruzi II (TC II) by the traditional genotyping method based on mini-exon gene employed in this study, were not nested within any of the previously defined TCII sublineages, constituting a new genotype designated as TCbat. Phylogenetic analyses demonstrated that TCbat indeed belongs to T. cruzi and not to other closely related bat trypanosomes of the subgenus Schizotrypanum, and that although separated by large genetic distances TCbat is closest to lineage TCI. A genotyping method targeting ITS1 rDNA distinguished TCbat from established T. cruzi lineages, and from other Schizotrypanum species. In experimentally infected mice, TCbat lacked virulence and yielded low parasitaemias. Isolates of TCbat presented distinctive morphological features and behaviour in triatomines. To date, TCbat genotype was found only in bats from anthropic environments of Central and Southeast Brazil. Our findings indicate that the complexity of T. cruzi is larger than currently known, and confirmed bats as important reservoirs and potential source of T. cruzi infections to humans.
The aim of this study was to evaluate the antimicrobial activity and toxicity of glass ionomer cement (GIC) modified with 5-methyl-2-(1-methylethyl)phenol (thymol) against Streptococcus mutans in ...silico and in vitro. The antimicrobial activity of thymol on GIC modified with concentrations of 2% (GIC-2) and 4% (GIC-4) was evaluated in a model of planktonic cell biofilm using agar diffusion test, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), dynamic biofilm (continuous flow cell parallel), and bacterial kinetics. Conventional GIC (GIC-0) was used as a control. Thymol toxicity was evaluated in Artemia salina and in silico using Osiris® software. Differences between groups were estimated by analysis of variance, followed by Tukey post hoc test, with a 5% significance level. The results of the agar diffusion test between groups were not significantly different (P≥0.05). Thymol had potential bacteriostatic and bactericidal activity against Streptococcus mutans with respect to planktonic growth, with MIC of 100 µg/mL and MBC of 400 µg/mL. The groups GIC-0, GIC-2, and GIC-4 reduced the biofilm by approximately 10, 85, and 95%, respectively. Bacterial kinetics showed efficiency of the modified GICs for up to 96 h. GIC with thymol was effective against S. mutans, with significant inhibition of the biofilms. Analyses in silico and using Artemia salina resulted in no relevant toxicity, suggesting potential for use in humans. GIC-2 was effective against S. mutans biofilm, with decreased cell viability.
Silage is a widespread practice to preserve forage. Poor storage conditions can lead to mold contamination and mycotoxin production. The aim of this study was to establish the occurrence of toxigenic ...fungal species and to determine aflatoxins (AFs), ochratoxin A (OTA), fumonisin B1 (FB1) and deoxinivalenol (DON) in corn silage intended for bovines before and after fermentation in farms located in São Paulo and Rio de Janeiro States, Brazil. Fungal counts were done by surface-spread method. Toxigenic ability of isolates was evaluated in vitro. AFs natural contamination was determined by TLC and HPLC. Total fungal counts were generally high. Aspergillus flavus, Penicillium citrinum, and Fusarium verticillioides were the prevalent species. Toxigenic strains were isolated. Aflatoxin levels differed (P < 0.0001) from 2 to 45 μg g−1 and from 2 to 100 μg g−1 in pre and post-fermentation samples, respectively. Ochratoxin A, FB1 and DON levels found in pre-fermentation samples were higher than in post-fermentation (P < 0.0001). Mycotoxins and toxigenic fungi were present before and after fermentation in corn silage intended for bovines in Brazil. Aflatoxin B1 (AFB1) increased during storage whereas OTA, FB1 and DON decreased. Determination of mycotoxin levels and their occurrence in corn silage are important to provide information so that the assessments of risk for animal feed and livestock environment could be made.
► Corn silage mycotoxicology in tropical climates has not been previously described. ► The occurrence of the main toxigenic fungal species was determined. ► Mycotoxins before and after silage fermentation were quantified. ► Fungi and mycotoxins contamination monitoring could prevent animal risk exposure.
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Hybrid lipid–polymer particles are gaining increasing interest to be applied as drug delivery systems due to their greater stability in biological fluids and enhanced cellular uptake ...of drugs. However, a major drawback is the fact that these particles are usually produced through techniques that use organic solvents. This work studies the possibility of producing for the first time hybrid particles composed by lipid multicores enveloped in a polymeric layer through Particles from Gas Saturated Solutions (PGSS®), without using organic solvents. An oil-in-water emulsion, composed by Gelucire 43/01™ (GEL) as the discontinuous phase and by an aqueous polyethylene glycol 4000 (PEG) solution as the continuous phase, was successfully precipitated by PGSS®. Operating conditions that ensured the stability of the CO2 saturated emulsion were previously evaluated. The resulting PEG–GEL particles present a spherical-like morphology constituted by several lipid cores encapsulated into a polymeric shell. The applicability of these structured particles to be used as drug delivery system (DDS) was studied by using ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID), as model drug. The particles provided an initial burst release of the drug due to the progressive dissolution of the external layer of PEG, followed by a controlled release of the NSAID from the GEL cores.
In the last years the environmental presence of pharmaceuticals has gained increasing attention. Research data show that these compounds can cause toxicological effects in different species of fish, ...mollusks and macroinvertebrates. However, the literature is scarce in terms of ecotoxicity data especially focusing on plants as test organisms. Ecotoxicological plant-based tests following the standard OEDC guideline 221 (OECD, 2006) are strongly restricted due to the recommended end-points: growth and yield of plants. It is necessary to develop and validate alternative macrophyte-based tests (non-standard endpoints), more sensible and providing additional information about the chemical contamination effects in plants. To attain this purpose, species from the Lemna genus were selected. Thus, the aim of this study was to analyze the toxic effects of pharmaceuticals in non-standard endpoints on two macrophyte species, Lemna minor and Lemna gibba. To this purpose an acute assay (96 h) was performed with L. minor and L. gibba exposed to chlorpromazine (CPZ), paracetamol (APAP), and diclofenac (DCF), in the following concentration ranges: 0 to 20 μg/L, 0 to 125 μg/L, and 0 to 100 μg/L, respectively. The analyzed endpoints were: levels of chlorophyll a and b, total chlorophyll, carotenoids, anthocyanins; chlorophyll fluorescence; and catalase activity. In general, higher concentrations of the tested pharmaceuticals caused significant effects on both Lemna species in terms of the different endpoints analyzed. In conclusion, acute exposures to CPZ, APAP, and DCF differently affected the defensive system of the tested species; among chlorophylls, chlorophyll b content was more affected, but pharmaceutical exposure was not able to cause alterations on chlorophyll fluorescence.
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•Chlorpromazine, paracetamol and diclofenac affected Lemna spp. defensive system.•Chlorophyll b was more sensitive endpoint than chlorophyll a to these drugs.•Chlorophyll fluorescence on Lemna spp. is not affected by these drugs.•Non-standard parameters are a promising tool for ecotoxicological evaluation.
Plectranthus barbatus Andrews (Lamiaceae) is widely distributed in the world and has a range of popular therapeutic indications. This work aimed to evaluate the phytochemical characterization of two ...leaf extracts of P. barbatus, and their antimicrobial, antineoplastic and immunomodulatory potential. After collection, herborization and obtainment of the P. barbatus aqueous extract (PBA) and acetone:water 7:3 P. barbatus organic extract (PBO), the phytochemical characterization was performed by high-performance liquid chromatography (HPLC). The antimicrobial activity was performed to determine the minimum inhibitory concentration (MIC) against eight bacterial strains using the microdilution test and the fungus Trichophyton rubrum by disc diffusion assay and microdilution test. Cytotoxicity was assessed by MTT and trypan blue methods in normal peripheral blood mononuclear cells (PBMCs) at concentrations ranged between 0.1 to 100 µg.mL-1 and in neoplastic cell lines Toledo, K562, DU-145 and PANC-1 at 1, 10 and 100 µg.mL-1 . Immunomodulatory activity, was evaluated by sandwich ELISA of proinflammatory cytokines at BALB/c mice splenocytes cultures supernatant. Both extracts presented flavonoids, cinnamic derivatives, steroids and ellagic acid. PBO showed bacteriostatic activity against Acinetobacter baumannii (MIC = 250 µg.mL-1) clinical isolate and PBA fungistatic activity against Trichophyton rubrum (MIC = 800 µg.mL-1). The extracts did not exhibit toxicity to PBMCs and neoplastic cells (IC50 > 100 µg.mL-1). Additionally, PBO at 100 µg.mL-1 significantly inhibited IFN-γ and IL-17A cytokines (p = 0.03). Plectranthus barbatus is a potential candidate for therapeutic use due to its low toxicity in healthy human cells and exhibits biological activities of medical interest as bacteriostatic, fungistatic and immunomodulatory.
Two experiments to determine the crude protein (CP) requirement of Heros severus were performed. Five isocaloric (3,200 kcal kg−1 of digestible energy) diets containing five levels of CP (28, 32, 36, ...40, and 44%) were evaluated. In the first, 75 fingerlings were distributed among 15 aquaria (30 L). In the second experiment, 100 juveniles were distributed among 20 aquaria (50 L). A quadratic effect on weight gain, specific growth rate for weight and for length, feed intake, feed conversion, body proteins, body lipids, and ash content of fingerlings occurred with increasing dietary CP, with optimum values estimated at 41.86, 40.30, 40.97, 39.60, 43.55, 40.64, 37.77, and 37.50% of CP, respectively. A linear effect on protein efficiency ratio of fingerlings occurred with increasing dietary CP. A quadratic effect on weight gain, specific growth rate for weight, feed conversion, hepatosomatic index, and body lipids of the juveniles were observed with increasing dietary CP, with optimum values estimated at 37.03, 37.20, 38.40, 35.13, 38.78, and 34,74% of CP, respectively. A linear effect on feed intake, protein efficiency ratio, and viscerosomatic index of juveniles occurred with increasing dietary CP. Blood glucose and hematocrit had lower values in juveniles fed a low level of CP.
Citric acid (CA) conditioning may be a promising alternative to ethylenediaminetetraacetic acid (EDTA) in regenerative endodontic procedures, as reported to improve growth factors' release from ...dentin. This review systematically investigated the effect of CA conditioning on the growth factors release from dentin and cell behavior compared to EDTA conditioning.
Searches were conducted (PubMed/MEDLINE, Scopus, Web of Science, Embase, SciELO, Cochrane Library, and grey literature) until May-2023. Only in vitro studies that evaluated the effects of CA on growth factors' release from dentin and cell behavior outcomes compared to EDTA were included. The studies were critically appraised using a modified Joanna Briggs Institute's checklist. Meta-analysis was unfeasible.
Out of the 335 articles screened, nine were included. Among these, three studies used dentin discs/roots from permanent human teeth; the rest combined them with stem cells. 10% CA for 5 or 10 minute was the most used protocol. Meanwhile, EDTA concentrations ranged from 10% to 17%. In eight studies examining the release of growth factors, five reported a significant release of transforming growth factor-β after dentin conditioning with 10% CA compared to 17% EDTA. Regarding cell behavior (6 studies), three studies assessed cell viability. The findings revealed that 10% CA conditioning showed cell viability similar to those of 17% EDTA. Additionally, in two out of three studies, it was observed that 10% CA conditioning did not affect cell morphology. The studies had a low risk of bias.
The use of 10% CA to condition dentin for 5-10 minutes resulted in a notable transforming growth factor -β1 release, but its cell responses were similar to those of EDTA.
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