Landfill leachates result from the degradation of solid residues in sanitary landfills, thus presenting a high variability in terms of composition. Normally, these effluents are characterized by high ...ammoniacal-nitrogen (N-NH₄⁺) concentrations, high chemical oxygen demands and low phosphorus concentrations. The development of effective treatment strategies becomes difficult, posing a serious problem to the environment. Phycoremediation appears to be a suitable alternative for the treatment of landfill leachates. In this study, the potential of
for biomass production and nutrients (mainly nitrogen and phosphorus) removal from different compositions of a landfill leachate was evaluated. Since microalgae also require phosphorus for their growth, different loads of this nutrient were evaluated, giving the following N:P ratios: 12:1, 23:1 and 35:1. The results have shown that
was able to grow in the different leachate compositions assessed. However, microalgal growth was higher in the cultures presenting the lowest N-NH₄⁺ concentration. In terms of nutrients uptake, an effective removal of N-NH₄⁺ and phosphorus was observed in all the experiments, especially in those supplied with phosphorus. Nevertheless, N-NO₃
removal was considered almost negligible. These promising results constitute important findings in the development of a bioremediation technology for the treatment of landfill leachates.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
Evidence regarding the impact of premature loss of primary molars on oral health‐related quality of life (OHRQoL) is lacking.
Aim
To evaluate the prevalence of premature loss of primary ...molars in schoolchildren and its impact on OHRQoL.
Design
We randomly selected 667 children aged 8‐9 years enrolled in public and private schools from Aracaju (Brazil). The presence of untreated dental caries and early loss of primary molars were recorded, and its impacts on OHRQoL evaluated using Child Perceptions Questionnaire (CPQ8‐10). Influence of some variables on tooth loss and OHRQoL was assessed by multilevel Poisson's regression analysis (P < 0.05).
Results
The prevalence for early tooth loss was 65.4% (95% confidence interval 51.1%‐77.3%). Children with untreated dental caries and attending public schools presented higher prevalence of early tooth loss. Moreover, early loss of primary molars provoked negative impact on OHRQoL considering total score of CPQ8‐10 and domains “oral symptoms,” “functional limitations” and “emotional well‐being.” Children presenting early teeth loss presented significantly higher scores of CPQ8‐10, as well as females and children with dental caries in other teeth.
Conclusions
The prevalence of early loss of primary molars is high, and it impacts the OHRQoL of children aged 8‐9 years.
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CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
This study evaluated the effects of Bifidobacterium animalis subsp. lactis HN019 (B. lactis HN019) in the development of periodontitis (PE), associated or not with metabolic syndrome, (MS) ...in rats.
Methods
Ninety‐six rats were grouped according to a food protocol: high‐fat diet for induction of MS or standard diet for the control groups (C). They were subdivided into groups with (+) and without (−) PE, receiving (*) or not (**) probiotic (PROB): C−**, CP−*, PE+**, PEP+*, MS− MSP−*, MSPE+**, and MSPEP+*. PROB administration started on the eighth week of the study and PE was induced on the 14th week by placing ligature on the animals' lower first molars. Euthanasia occurred in the 16th week. Biomolecular analyzes, immunoenzymatic assays, and microtomographic analyses were performed. The data obtained were analyzed statistically (P < 0.05).
Results
The PEP and MSPEP groups showed lower levels of alveolar bone loss when compared with the PE and MSPE groups, respectively (P < 0.05). The immunoenzymatic analysis showed higher levels of interleukin (IL)‐1β and a higher receptor activator of NF‐kappaB ligand (RANKL)/osteoprotegerin (OPG) ratio in the MSPE group when compared with the MSPEP group (P < 0.05). The PEP group showed lower levels of tumor necrosis factor (TNF)‐α and IL–6 when compared with the PE group. The use of PROB attenuated dyslipidemia parameters in animals with MS, with or without PE.
Conclusion
B. lactis HN019 reduced more significantly the severity of PE in rats with MS, modulating both systemic metabolic and immunoinflammatory parameters in periodontal tissues.
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BFBNIB, CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Dengue outbreaks can affect 390 million persons yearly. In a trial involving 16,235 persons in Brazil, the live, attenuated, tetravalent Butantan vaccine was efficacious in all age groups at 2 years.
The Zika virus (ZIKV) is a neurotropic arbovirus considered a global threat to public health. Although there have been several efforts in drug discovery projects for ZIKV in recent years, there are ...still no antiviral drugs approved to date. Here, we describe the results of a global collaborative crowdsourced open science project, the OpenZika project, from IBM’s World Community Grid (WCG), which integrates different computational and experimental strategies for advancing a drug candidate for ZIKV. Initially, molecular docking protocols were developed to identify potential inhibitors of ZIKV NS5 RNA-dependent RNA polymerase (NS5 RdRp), NS3 protease (NS2B-NS3pro), and NS3 helicase (NS3hel). Then, a machine learning (ML) model was built to distinguish active vs inactive compounds for the cytoprotective effect against ZIKV infection. We performed three independent target-based virtual screening campaigns (NS5 RdRp, NS2B-NS3pro, and NS3hel), followed by predictions by the ML model and other filters, and prioritized a total of 61 compounds for further testing in enzymatic and phenotypic assays. This yielded five non-nucleoside compounds which showed inhibitory activity against ZIKV NS5 RdRp in enzymatic assays (IC50 range from 0.61 to 17 μM). Two compounds thermally destabilized NS3hel and showed binding affinity in the micromolar range (K d range from 9 to 35 μM). Moreover, the compounds LabMol-301 inhibited both NS5 RdRp and NS2B-NS3pro (IC50 of 0.8 and 7.4 μM, respectively) and LabMol-212 thermally destabilized the ZIKV NS3hel (Kd of 35 μM). Both also protected cells from death induced by ZIKV infection in in vitro cell-based assays. However, while eight compounds (including LabMol-301 and LabMol-212) showed a cytoprotective effect and prevented ZIKV-induced cell death, agreeing with our ML model for prediction of this cytoprotective effect, no compound showed a direct antiviral effect against ZIKV. Thus, the new scaffolds discovered here are promising hits for future structural optimization and for advancing the discovery of further drug candidates for ZIKV. Furthermore, this work has demonstrated the importance of the integration of computational and experimental approaches, as well as the potential of large-scale collaborative networks to advance drug discovery projects for neglected diseases and emerging viruses, despite the lack of available direct antiviral activity and cytoprotective effect data, that reflects on the assertiveness of the computational predictions. The importance of these efforts rests with the need to be prepared for future viral epidemic and pandemic outbreaks.
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IJS, KILJ, NUK, PNG, UL, UM
Resumo Fundamento O maior risco de se desenvolver diabetes com o uso de estatinas é um desafio para a segurança do uso dessa classe de medicamentos em longo prazo. No entanto, poucos estudos ...analisaram essa questão durante síndromes coronarianas agudas (SCA). Objetivos Investigar a associação entre início precoce da terapia com estatina e níveis de glicemia em pacientes admitidos com SCA. Métodos Este foi um estudo retrospectivo de pacientes hospitalizados por SCA. Pacientes que nunca haviam usado estatinas foram incluídos e divididos segundo uso ou não de estatina nas primeiras 24 horas de internação. O desfecho primário foi a incidência de hiperglicemia na internação (definida como pico de glicemia > 200mg/dL). Modelos de regressão logística e modelos lineares multivariados foram usados para ajuste quanto a fatores de confusão e um modelo de pareamento por escore de propensão foi desenvolvido para comparações entre os dois grupos de interesses. Um valor de p menor que 0,05 foi considerado estatisticamente significativo. Resultados Um total de 2357 pacientes foram incluídos, 1704 deles alocados no grupo que receberam estatinas e 653 no grupo que não receberam estatinas nas primeiras 24 horas de internação. Após os ajustes, uso de estatina nas primeiras 24 horas foi associado com uma menor incidência de hiperglicemia durante a internação (OR ajustado = 0,61, IC95% 0,46-0,80; p < 0,001) e menor necessidade de uso de insulina (OR ajustado = 0,56, IC 95% 0,41-0,76; p < 0,001). Essas associações mantiveram-se similares nos modelos de pareamento por escore de propensão, bem como após análises de sensibilidade, como exclusão de pacientes que desenvolveram choque cardiogênico, infecção grave ou pacientes que foram a óbito durante a internação hospitalar. Conclusões Entre os pacientes internados com SCA que não receberam estatinas previamente, a terapia precoce com estatina associou-se independentemente com menor incidência de hiperglicemia durante a internação. (Arq Bras Cardiol. 2021; 116(2):285-294)
Background & Aims
To study immunological mechanisms of fulminant hepatic failure (FHF) derived from extensive liver lesions, 14 patients with FHF induced by different aetiologies were investigated by ...observance of both lymphocyte phenotyping and cytokine levels.
Methods
Five patients bearing benign acute hepatitis B (AHB) and seven healthy liver donors (HC) were used as controls. Samples of liver and blood from both FHF patients and HC were obtained during transplantation procedures. Plasma levels of IL‐1β, IL‐4, IL‐6, IL‐8, IL‐10, IFN‐γ, TNF‐α, MCP‐1, RANTES and MIP‐1α were quantified using a multiplex immunoassay. Cell characterization was carried out by flow cytometry. IFN‐γ staining was performed on liver sections using immunofluorescence methods.
Results
An increase of peripheral frequency of natural killer (NK) cells expressing early activation markers (CD69, HLA‐DR and CD38) and adhesion molecule CD44 was observed in FHF patients. Elevated frequency of T lymphocytes CD4+ and CD8+ expressing CD38 and adhesion molecules CD29 and CD44 was also observed in FHF. Additionally, an increase of natural killer T cells (NKT) was detected in FHF patients. High plasma cytokine levels were not statistically different between FHF and AHB patients. In comparison to HC, a strong liver expression of IFN‐γ was detected in FHF patients. The increased frequency of CD4+CD44+ and IL‐8 cytokine was found in patients with poor prognosis.
Conclusions
These findings indicate the involvement of NK and NKT cells as well as T lymphocytes CD4+ and CD8+ in the inflammatory process inducing FHF, confirmed by the high hepatic expression of IFN‐γ.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in ...advancing our understanding of brain processes in the epilepsies. Smaller‐scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well‐established by the ENIGMA Consortium, ENIGMA‐Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event‐based modeling analysis. We explore age of onset‐ and duration‐related features, as well as phenomena‐specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA‐Epilepsy.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background:
The sonic hedgehog (SHH) pathway plays a key role in rodent adrenal cortex development and is involved in tumorigenesis in several human tissues, but data in human adrenal glands are ...limited.
Objectives:
The objectives of the study were to analyze the involvement of the SHH pathway in human adrenal development and tumorigenesis and the effects of SHH inhibition on an adrenocortical tumor (ACT) cell line.
Patients and Methods:
Expression of SHH pathway components was evaluated by immunohistochemistry in 51 normal adrenals (33 fetal) and 34 ACTs (23 pediatric) and by quantitative PCR in 81 ACTs (61 pediatric) and 19 controls (10 pediatric). The effects of SHH pathway inhibition on gene expression and cell viability in the NCI-H295A adrenocortical tumor cell line after cyclopamine treatment were analyzed.
Results:
SHH pathway proteins were present in fetal and postnatal normal adrenals and showed distinct patterns of spatiotemporal expression throughout development. Adult adrenocortical carcinomas presented with higher expression of PTCH1, SMO, GLI3, and SUFU compared with normal adult adrenal cortices. Conversely, pediatric ACTs showed lower mRNA expression of SHH, PTCH1, SMO, GLI1, and GLI3 compared with normal pediatric adrenal cortices. In vitro treatment with cyclopamine resulted in decreased GLI3, SFRP1, and CTNNB1 mRNA expression and β-catenin staining as well as decreased cell viability.
Conclusions:
The SHH pathway is active in human fetal and postnatal adrenals, up-regulated in adult adrenocortical carcinomas, and down-regulated in pediatric ACTs. SHH pathway antagonism impaired cell viability. The SHH pathway is deregulated in ACTs and might provide a new target therapy to be explored.
The natural fatty acids (5Z)-5-pentacosenoic and (9Z)-9-pentacosenoic acids were synthesized for the first time in eight steps starting from either 4-bromo-1-butanol or 8-bromo-1-butanol and in ...20–58 % overall yields, while the novel fatty acids 5-pentacosynoic and 9-pentacosynoic acids were also synthesized in six steps and in 34–43 % overall yields. The ∆⁵ acids displayed the best IC₅₀’ₛ (24–38 µM) against the HIV-1 reverse transcriptase (RT) enzyme, comparable to nervonic acid (IC₅₀ = 12 µM). The ∆⁹ acids were not as effective towards HIV-RT with the (9Z)-9-pentacosenoic acid displaying an IC₅₀ = 54 µM and the 9-pentacosynoic acid not inhibiting the enzyme at all. Fatty acid chain length and position of the unsaturation was important for the observed inhibition. None of the synthesized fatty acids were toxic (IC₅₀ > 500 µM) towards peripheral blood mononuclear cells. Molecular modeling studies indicated the structural determinants underlying the biological activity of the most potent compounds. These results provide new insights into the structural requirements that must be present in fatty acids so as to enhance their inhibitory potential towards HIV-RT.
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FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UL, UM, UPUK, VKSCE, ZAGLJ
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