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Blau syndrome is an autosomal dominant chronic inflammatory disease, which may begin with skin manifestations in the first months of life, alerting physicians to the diagnosis. This case reports a patient diagnosed jointly by pediatric dermatology and rheumatology consultants at two years of age.
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Artritis , Sarcoidosis , Sinovitis , Uveítis , Humanos , Sinovitis/genética , Sinovitis/diagnóstico , Uveítis/diagnóstico , Sarcoidosis/diagnóstico , Sarcoidosis/patología , Artritis/diagnóstico , Preescolar , Masculino , Femenino , Artritis Infecciosa/diagnóstico , Enfermedades Autoinflamatorias HereditariasRESUMEN
Antimicrobial resistance (AMR) is one of humanity's main health problems today. Despite all the breakthroughs and research over the past few years, the number of microbial illnesses that are resistant to the available antibiotics is increasing at an alarming rate. In this article, we estimated the biomedical potential of Portuguese propolis harvested from the Gerês apiary over five years, evaluating the in vitro antimicrobial effect of five hydroalcoholic extracts prepared from five single propolis samples and of a hydroalcoholic extract obtained from the mixture of all samples. The antimicrobial potential was firstly assessed by determining the minimum inhibitory concentration (MIC) of these extracts against a panel of three Gram-positive (Bacillus subtilis, methicillin-sensitive Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus) and one Gram-negative bacteria (Escherichia coli), as well as two yeasts (Candida albicans and Saccharomyces cerevisiae). As MIC values against each bacterium were consistent across all the evaluated propolis extracts, we decided to further conduct a disk diffusion assay, which included three commercial antibiotics-erythromycin, vancomycin, and amoxicillin/clavulanic acid-for comparison purposes. In addition to displaying a concentration-dependent antibacterial effect, the hydroalcoholic extracts prepared with 70% ethanol exhibited stronger antimicrobial capacity than vancomycin against B. subtilis (% of increase ranged between 26 and 59%) and methicillin-sensitive S. aureus (% of increase ranged between 63 and 77%). Moreover, methicillin-resistant S. aureus (MRSA) showed susceptibility to the activity of the same extracts and resistance to all tested antibiotics. These findings support that propolis from Gerês is a promising natural product with promising antimicrobial activity, representing a very stimulating result considering the actual problem with AMR.
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INTRODUCTION: Peripheral arterial disease (PAD) is an occlusive atherosclerotic disease of the arteries of the extremities of the body that affects more than 230 million people worldwide. The most common symptom is intermittent claudication, described as leg pain which occurs mainly while walking. The symptoms impair the ambulation and functional capacity of patients, leading to loss of mobility, disease deterioration, increased risk of other cardiovascular diseases, and lower quality of life (QoL). Therefore, the aim of this study was to perform a cross-cultural adaptation and validation of the VascuQol-6 questionnaire for the Portuguese population to obtain a quick, sensitive, and easy-to-use way to assess the QoL of Portuguese patients diagnosed with PAD. METHODS: The Vascular Quality of Life-6 Questionnaire (VascuQoL-6) was adapted and translated into European Portuguese using standard validation methodology, including 115 patients with a mean age of 64.67 (7.23) years, with PAD with IC stable for more than three months; and ABI < 0.9 at rest. VascuQoL-6, SF-36, International Physical Activity Questionnaire (IPAQ), and the PAD Knowledge Questionnaire (PADKQ) were used. Reliability, construct validity analysis through convergent and discriminant validity, known-group validity, and responsiveness analysis were tested. RESULTS: The Cronbach's alpha was 0.64 and the average inter-item correlation was 0.27, indicating acceptable internal consistency. VascuQoL-6 was positively associated with SF-36 Physical Component Summary and Mental Component Summary scores (r = 0.64, p < 0.01 and r = 0.42, p < 0.01, respectively). In turn, there was no significant correlation between VascuQoL-6 scores and the PADKQ or IPAQ. A statistically significant difference between groups according to IC severity [F(2.47) = 8.35, p < 0.001] was found. A paired samples t-test showed differences between VascuQol-6 scores before a walking program (M = 15.65, SD = 3.09), and after a walking program (M = 17.41, SD = 2.71), t(67) = 3.94, p ≤ 0.001. CONCLUSION: The VascuQoL-6 is a six-item instrument to assess the QoL associated with PAD with good psychometric properties, convergent and discriminant validity with SF-36, PADKQ and IPAQ. The instrument proved to have known group validity and responsiveness.
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Enfermedad Arterial Periférica , Calidad de Vida , Traducciones , Humanos , Enfermedad Arterial Periférica/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Portugal , Anciano , Encuestas y Cuestionarios/normas , Reproducibilidad de los Resultados , Características CulturalesRESUMEN
COVID-19, caused by SARS-CoV-2, affects neuronal cells, causing several symptoms such as memory loss, anosmia and brain inflammation. Curcuminoids (Me08 e Me23) and curcumin (CUR) are derived from Curcuma Longa extract (EXT). Many therapeutic actions have been linked to these compounds, including antiviral action. Given the severe implications of COVID-19, especially within the central nervous system, our study aims to shed light on the therapeutic potential of curcuminoids against SARS-CoV-2 infection, particularly in neuronal cells. Here, we investigated the effects of CUR, EXT, Me08 and Me23 in human neuroblastoma SH-SY5Y. We observed that Me23 significantly decreased the expression of plasma membrane-associated transmembrane protease serine 2 (TMPRSS2) and TMPRSS11D, consequently mitigating the elevated ROS levels induced by SARS-CoV-2. Furthermore, Me23 exhibited antioxidative properties by increasing NRF2 gene expression and restoring NQO1 activity following SARS-CoV-2 infection. Both Me08 and Me23 effectively reduced SARS-CoV-2 replication in SH-SY5Y cells overexpressing ACE2 (SH-ACE2). Additionally, all of these compounds demonstrated the ability to decrease proinflammatory cytokines such as IL-6, TNF-α, and IL-17, while Me08 specifically reduced INF-γ levels. Our findings suggest that curcuminoid Me23 could serve as a potential agent for mitigating the impact of COVID-19, particularly within the context of central nervous system involvement.
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Antiinflamatorios , Antioxidantes , Antivirales , Tratamiento Farmacológico de COVID-19 , Curcumina , SARS-CoV-2 , Humanos , Curcumina/farmacología , Curcumina/análogos & derivados , Antioxidantes/farmacología , Antivirales/farmacología , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/fisiología , Antiinflamatorios/farmacología , Línea Celular Tumoral , Curcuma/química , Serina Endopeptidasas/metabolismo , COVID-19/virología , COVID-19/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Extractos Vegetales/farmacología , Citocinas/metabolismo , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/virologíaRESUMEN
In response to excessive DNA damage, human cells can activate p53 to induce apoptosis. Cells lacking p53 can still undergo apoptosis upon DNA damage, yet the responsible pathways are unknown. We observed that p53-independent apoptosis in response to DNA damage coincided with translation inhibition, which was characterized by ribosome stalling on rare leucine-encoding UUA codons and globally curtailed translation initiation. A genetic screen identified the transfer RNAse SLFN11 and the kinase GCN2 as factors required for UUA stalling and global translation inhibition, respectively. Stalled ribosomes activated a ribotoxic stress signal conveyed by the ribosome sensor ZAKα to the apoptosis machinery. These results provide an explanation for the frequent inactivation of SLFN11 in chemotherapy-unresponsive tumors and highlight ribosome stalling as a signaling event affecting cell fate in response to DNA damage.
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Apoptosis , Daño del ADN , Biosíntesis de Proteínas , Ribosomas , Proteína p53 Supresora de Tumor , Humanos , Línea Celular Tumoral , Codón/genética , Leucina/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Ribosomas/metabolismo , Transducción de Señal , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Quinasas Quinasa Quinasa PAM/genética , Quinasas Quinasa Quinasa PAM/metabolismoRESUMEN
Intermittent claudication is the most common symptom of Peripheral Arterial Disease (PAD) and is associated with decreased quality of life (QoL) due to walking impairment. The level of threat attributed to the disease affects QoL and physical activity. This study explores beliefs and illness drawings, and their relationship with quality of life and physical activity in patients undergoing conservative treatment for PAD. A cross-sectional study was carried out including 119 patients with PAD and Intermittent Claudication, in which patients were asked to freely draw their disease and 33 agreed to participate. The profile of beliefs about PAD is characterized by a low level of threat. Belief in the emotional impact of the disease, representations about the consequences and concern about the disease were associated with worse quality of life; the belief of having a high personal control over the disease was associated with more physical activity. The analysis of the disease drawings revealed three categories: extension of the disease (category 1), location and representations of the disease (category 2), and level of detail and complexity of the drawings (category 3). Greater disease extent was associated with more disease symptoms (IPQ 6) (rs = 0.399, p = .021). It is necessary to address beliefs and representations about the disease in consultations with patients with PAD. Patient drawings are a useful, practical, and free tool that does not require a lot of time and can facilitate the approach of health professionals to patient training and education.
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Ejercicio Físico , Claudicación Intermitente , Enfermedad Arterial Periférica , Calidad de Vida , Humanos , Calidad de Vida/psicología , Masculino , Femenino , Enfermedad Arterial Periférica/psicología , Estudios Transversales , Anciano , Ejercicio Físico/psicología , Persona de Mediana Edad , Claudicación Intermitente/psicología , Conocimientos, Actitudes y Práctica en Salud , Anciano de 80 o más AñosRESUMEN
Chronic myeloid leukemia (CML) is a type of leukemia whose main genetic marker is the reciprocal translocation that leads to the production of the BCR::ABL1 oncoprotein. The expression of some genes may interfere with the progression and development of leukemias. MicroRNAs are small non-coding RNAs that have the potential to alter the expression of some genes and may be correlated with some types of leukemia and could be used as biomarkers in the diagnosis and prognosis of patients. Therefore, this project carried out an analysis of microRNA-type plasma biomarkers in patients with chronic myeloid leukemia at unique points, including follow-up analysis of patients from the Erasto Gaertner Hospital. 35 microRNAs were analyzed in different cohorts. Inside those groups, 70 samples were analyzed at unique points and 11 patients in a follow-up analysis. Statistically different results were found for microRNA-7-5p, which was found to be upregulated in patients with high expression of the BCR::ABL1 transcript when compared to healthy controls. This microRNA also had evidence of behavior related to BCR::ABL1 when analyzed in follow-up, but strong evidence was not found. In this way, this work obtained results that may lead to manifestations of a relationship between miR-7-5p and chronic myeloid leukemia, and evaluations of possible microRNAs that are not related to this pathology.
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Leucemia Mielógena Crónica BCR-ABL Positiva , MicroARNs , Humanos , MicroARNs/genética , Proteínas de Fusión bcr-abl/genética , Proteínas de Fusión bcr-abl/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Translocación Genética , BiomarcadoresRESUMEN
BACKGROUND: The effects of SARS-CoV-2 gestational exposure on child development remain inconclusive. AIMS: To analyze the effects of SARS-CoV-2 gestational exposure on neurodevelopment until 12 months. STUDY DESIGN: Prospective cohort study conducted in five municipalities in Southeast Brazil from August 2021 to September 2022. SUBJECTS: Infants were recruited from a serological survey performed during neonatal screening and followed up to 12 months old. We included 224 infants exposed to SARS-CoV-2 during pregnancy and 225 non-exposed, according to the serology results of the newborn as well as their mothers and the maternal antenatal RT-PCR results. OUTCOME MEASURES: Developmental assessments were performed at 6 and 12 months using the Survey of Wellbeing of Young Children-Brazilian Version (SWYC-BR). Children with suspected developmental delay (SDD) at 6 and 12 months were considered at high risk for developmental delay (HRDD). Additionally, risk factors associated with SDD were examined. RESULTS: There were 111 children identified with SDD and 52 with HRDD. SARS-CoV-2 gestational exposure was not associated with SDD. Exposure in the first gestational trimester increased SDD risk by 2.15 times compared to the third. Cesarean delivery predicted SDD (OR 1.56; 95%CI 1.01-2.42) and HRDD (OR 1.91; 95%CI 1.04-3.48). Additionally, suspected maternal depression predicted SDD (OR 1.76; 95%CI 1.01-3.10). CONCLUSION: SARS-CoV-2 gestational exposure did not increase the developmental delay risk. However, our findings suggest that the earlier the gestational exposure, the greater the developmental delay risk at 12 months. Cesarean delivery and suspected maternal depression increased the developmental delay risk, independent of virus exposure.
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COVID-19 , Complicaciones Infecciosas del Embarazo , Lactante , Recién Nacido , Niño , Humanos , Embarazo , Femenino , Preescolar , SARS-CoV-2 , Brasil/epidemiología , Estudios Prospectivos , COVID-19/epidemiología , Factores de Riesgo , Complicaciones Infecciosas del Embarazo/epidemiologíaRESUMEN
This study investigated the genotoxic risk of chronic exposure of hemolymph's cells of Drosophila melanogaster (Insecta, Diptera) to water samples from Boqueirão de Parelhas Dam and from Lucrécia Dam in the semiarid region of Brazil. The dams are located over the Pegmatite Province of Borborema, with rocks rich in uranium and thorium. Water samples hydrated a culture medium composed of mashed potatoes, where larvae of D. melanogaster fed for 24 h, before be underwent to the Comet assay. The same water was evaluated for the presence of dissolved Radon gas (222Rn) and concentrations of 11 toxic metals (Ag, Al, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn). The results indicated a genotoxic effect resulting from exposure to the waters of the Parelhas dam, in the samples of August 2018; and in Lucrécia dam, in January 2019. D. melanogaster stood out for its high sensitivity to monitor the genotoxic effects of compounds dissolved in public dams. And unlike to other essentially aquatic sentinel organisms, this species stood out as a model to concomitant studies of air and water possible contaminated, in a scenario of natural environmental radioactivity present in semiarid of Brazil.
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Metales Pesados , Contaminantes Químicos del Agua , Animales , Drosophila melanogaster , Monitoreo del Ambiente/métodos , Especies Centinela , Agua , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis , Brasil , Ingestión de Alimentos , Metales Pesados/análisisRESUMEN
Aims: Investigate whether a Home-based Exercise Therapy (HBET) program for patients with Peripheral Arterial Disease (PAD) and Intermittent Claudication (IC) with a behavior change intervention, supported by a smartphone application, is effective in improving walking distances and performance, and quality of life (QoL) over 6 months. Methods and results: This was a single-center, prospective, two-arm, single-blinded randomized controlled trial including 73 patients with PAD and IC, and three assessment moments: baseline, 3, and 6 months. Participants were randomized to receive a walking exercise prescription, with the support (n = 38) or without the support (n = 35) of the WalkingPad app, between January 2021 and July 2022. Both groups received two face-to-face behavior change sessions and 12 structured and targeted reinforcement phone calls over 6 months. Primary outcomes were between-group differences in pain-free walking distance (PFWD), functional walking distance (FWD), maximal walking distance (MWD), and 6-min walk distance (6â MWD) at 3 and 6 months. Secondary outcomes were QoL and walking impairment. Seventy-three patients (mean age 64 ± 7.2 years, 88% men) participated in this study, 60 of whom completed the three assessment moments. The whole sample significantly improved all primary outcomes in the first 3 months; that is, the average PFWD (151.1â m), FWD (175.2â m), MWD (171.1â m), and 6â MWD (30.8â m) increased from T1 to T2. Only MWD exhibited a significant average increase (35.0â m). Secondary outcomes also increased from baseline to 3 and 6 months. There were no between-group differences, except for MWD, which showed a greater increase at 6 months in the group that used the app, excluding patients with weak walking ability and extreme anxiety symptoms at baseline. Conclusion: The intervention improved distances and walking skills as well as the physical, mental, and disease-related quality of life among adults with PAD and IC. The group that used the WalkingPad app improved their MWD in 6 months compared to the control group, except for patients with poor walking ability and extreme anxiety symptoms, which suggests the effectiveness of the WalkingPad app for patients with high walking ability and no severe anxiety symptoms. More research is needed to determine the durability of these findings and to explore what app functionality might promote the other outcomes. Clinical Trial Registration: https://clinicaltrials.gov (NCT04749732).
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Evaluating the efficiency of surface treatments is a problem of paramount importance for the cork stopper industry. Generically, these treatments create coatings that aim to enhance the impermeability and lubrification of cork stoppers. Yet, current methods of surface analysis are typically time-consuming, destructive, have poor representativity or rely on indirect approaches. In this work, the use of a laser-induced breakdown spectroscopy (LIBS) imaging solution is explored for evaluating the presence of coating along the cylindrical surface and in depth. To test it, several cork stoppers with different shaped areas of untreated surface were analyzed by LIBS, making a rectangular grid of spots with multiple shots per spot, to try to identify the correspondent shape. Results show that this technique can detect the untreated area along with other features, such as leakage and holes, allowing for a high success rate of identification and for its performance at different depths, paving the way for future industry-grade quality control solutions with more complex surface analysis.
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Propolis, a natural resin created by bees, has garnered significant attention from both the scientific community and industry due to an impressive range of bioactivities. Nonetheless, the intrinsic variability in its chemical composition and bioactive profiles has been hindering propolis' full potential use. We previously showed that ethanol extracts (EEs) of a Portuguese propolis sample (Gerês) collected over four consecutive years displayed similar chemical and biological profiles, a constancy never documented before. However, the characteristics of the unprocessed samples of Gerês propolis were never described. Hence, the central objective of this study is to assess the quality parameters of unprocessed propolis samples collected from Gerês (G), over a four-year period (2019-2022), alongside the analysis of the chemical composition and bioactivities of the EEs prepared with the same raw samples. The ash, wax, balsam and water contents of the unprocessed samples-G19 to G22-showed minor fluctuations, likely attributed to uncontrollable natural events impacting the propolis source and collection process. On the other hand, the antimicrobial and antioxidant activities of all the four ethanol extracts (G19.EE-G22.EE) consistently align with prior studies. Furthermore, the Gerês propolis extracts showed remarkable uniformity in chemical composition parameters too, particularly concerning total polyphenol, flavonoid and ortho-diphenol contents. In summary, our research reinforces the beneficial properties of propolis and show that extracts' bioactivities remain within the reference ranges for Gerês propolis, despite minor differences in unprocessed samples, suggesting a consistent action over time. Thus, this work could be instrumental towards the establishment of standard parameters for propolis applications, offering valuable insights to this field of propolis research.
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Triacylglycerols (TAGs) are the main source of stored energy in the body, providing an important substrate pool for mitochondrial beta-oxidation. Imbalances in the amount of TAGs are associated with obesity, cardiac disease and various other pathologies1,2. In humans, TAGs are synthesized from excess, coenzyme A-conjugated fatty acids by diacylglycerol O-acyltransferases (DGAT1 and DGAT2)3. In other organisms, this activity is complemented by additional enzymes4, but whether such alternative pathways exist in humans remains unknown. Here we disrupt the DGAT pathway in haploid human cells and use iterative genetics to reveal an unrelated TAG-synthesizing system composed of a protein we called DIESL (also known as TMEM68, an acyltransferase of previously unknown function) and its regulator TMX1. Mechanistically, TMX1 binds to and controls DIESL at the endoplasmic reticulum, and loss of TMX1 leads to the unconstrained formation of DIESL-dependent lipid droplets. DIESL is an autonomous TAG synthase, and expression of human DIESL in Escherichia coli endows this organism with the ability to synthesize TAG. Although both DIESL and the DGATs function as diacylglycerol acyltransferases, they contribute to the cellular TAG pool under specific conditions. Functionally, DIESL synthesizes TAG at the expense of membrane phospholipids and maintains mitochondrial function during periods of extracellular lipid starvation. In mice, DIESL deficiency impedes rapid postnatal growth and affects energy homeostasis during changes in nutrient availability. We have therefore identified an alternative TAG biosynthetic pathway driven by DIESL under potent control by TMX1.
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Aciltransferasas , Triglicéridos , Animales , Humanos , Ratones , Aciltransferasas/metabolismo , Coenzima A/metabolismo , Diacilglicerol O-Acetiltransferasa/metabolismo , Escherichia coli/metabolismo , Homeostasis , Triglicéridos/biosíntesis , Metabolismo Energético , Nutrientes/metabolismo , Ácidos Grasos/química , Ácidos Grasos/metabolismoRESUMEN
Introdução: O efeito branqueador dos dentifrícios contendo Blue covarine é fundamentado no seu mecanismo de ação, caracterizado pela sua deposição na superfície dentária, alterando a percepção da cor. Objetivo: Revisar a literatura e buscar evidência científica sobre o efeito branqueador do Blue Covarine em tecidos mineralizados e materiais restauradores estéticos. Materiais e métodos: Para a revisão da literatura foram feitas buscas nas bases de dados PubMed, LILACS, BBO, SciELO e MEDLINE para identificar estudos clínicos e laboratoriais que avaliassem a ação branqueadora do agente óptico Blue covarine. Como estratégia de busca foram utilizados os descritores "Blue covarine", "Blue covarine e pasta de dentes", "Blue covarine and toothpaste", "Blue covarine e dentifrícios", "Blue covarine and dentifrices", "Blue covarine e dentifrícios branqueadores", "Blue covarine and whitening dentifrices", "Blue covarine e dentifrícios clareadores", "Blue covarine and bleaching dentifrices", "Blue covarine e pasta de dentes branqueadoras", "Blue covarine and whitening toothpaste", "Blue covarine e pasta de dentes clareadoras", "Blue covarine and bleaching toothpaste". Resultados: Dois pesquisadores selecionaram e analisaram criticamente 31 artigos, sendo 2 revisões da literatura, 4 estudos clínicos e 25 estudos laboratoriais. Divergências quanto ao desenho de estudo, métodos, amostra, critérios clínicos e parâmetros laboratoriais foram observados, além de conflitos de interesse. Conclusão: O Blue Covarine presente nos dentifrícios branqueadores parece ser efetivo na promoção do branqueamento dentário apenas quando associado aos agentes abrasivos presentes nas formulações, evidenciando que ensaios clínicos e laboratoriais, com metodologias semelhantes, são necessários para se obter evidência científica conclusiva sobre o efeito deste agente branqueador.(AU)
Introduction: The whitening effect of dentifrices containing Blue Covarine is based on its mechanism of action, characterized by its deposition on the tooth surface, altering the perception of color. Objective: To review the literature and seek scientific evidence on the whitening effect of Blue Covarine on mineralized tissues and aesthetic restorative materials. Materials and methods: For the literature review, searches were carried out in the PubMed, LILACS, BBO, SciELO and MEDLINE databases, in order to identify clinical and laboratory studies that evaluated the whitening action of the optical agent Blue Covarine. As a search strategy, the descriptors "Blue Covarine", "Blue Covarine and toothpaste", "Blue Covarine and dentifrices", "Blue Covarine and whitening dentifrices", "Blue Covarine and bleaching dentifrices", "Blue Covarine and whitening toothpaste", "Blue Covarine and bleaching toothpaste". Results: Two researchers selected and critically analyzed 31 articles, including 2 literature reviews, 4 clinical studies and 25 laboratory studies. Differences in study design, methods, sample, clinical criteria and laboratory parameters were observed, in addition to conflicts of interest. Conclusion: Blue Covarine present in whitening dentifrices seems to be effective in promoting dental whitening only when associated with abrasive agents present in the formulations, showing that clinical and laboratory tests, with similar methodologies, are necessary to obtain conclusive scientific evidence on the effect of this bleaching agent.(AU)
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Humanos , Blanqueamiento de Dientes/métodos , Dentífricos/química , Isoindoles/química , Blanqueadores Dentales/química , Metaloporfirinas/química , Colorimetría , Esmalte Dental/químicaRESUMEN
This article addresses a gap in the literature regarding the design and implementation of health and well-being strategies by local governments. It presents a conceptual framework that can help local governments to include health and well-being among their political priorities by promoting the participation of local stakeholders and the community in general. The article also highlights the important role that local governments play in public health, especially in times of crisis, such as the COVID-19 pandemic. To demonstrate the approach, the manuscript explores the recent shift toward decentralization in Portugal and the resulting emphasis on local governments leading new approaches to health governance. The planning process for Arouca's Health Strategy, an inland municipality, is used as a case study to demonstrate the approach, which emphasizes the meaningful participation of the entire local community. The article concludes by noting that there is still significant room for improvement in all areas related to health and well-being and a need to adopt new multistakeholder governance arrangements to sustain the institutional capacity for upcoming strategies.
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COVID-19 , Gobierno Local , Humanos , Pandemias/prevención & control , COVID-19/epidemiología , COVID-19/prevención & control , Ciudades , PortugalRESUMEN
Chagas disease is derived from the infection by the protozoan Trypanosoma cruzi. In many countries, benznidazole is the only drug approved for clinical use despite several side effects and the emergence of resistant parasite strains. In this context, our group has previously pointed out that two novel aminopyridine derivatives complexed with Cu2+, namely, cis-aquadichloro(N-[4-(hydroxyphenyl)methyl]-2-pyridinemethamino)copper (3a) and its glycosylated ligand cis-dichloro (N-{[4-(2,3,4,6-tetra-O-acetyl-ß-D-glucopyranosyloxy)pheny]lmethyl}-2-pyridinemethamino)copper (3b), are effective against T. cruzi trypomastigote forms. With this result in mind, the present work aimed to investigate the effects of both compounds on trypomastigotes physiology and on the interaction process with host cells. Apart from loss of plasma membrane integrity, an increased generation of reactive oxygen species (ROS) and decreased mitochondrial metabolism were observed. Pretreatment of trypomastigotes with these metallodrugs inhibited the association index with LLC-MK2 cells in a typical dose-dependent manner. Both compounds showed low toxicity on mammalian cells (CC50 > 100 µM), and the IC50 values calculated for intracellular amastigotes were determined as 14.4 µM for 3a and 27.1 µM for 3b. This set of results demonstrates the potential of these aminopyridines complexed with Cu2+ as promising candidates for further antitrypanosomal drug development.
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Among the 13 types of propolis classified in Brazil according to their physicochemical properties, green propolis and brown propolis are the most commonly found and used. In this work, a comparison of the physicochemical properties of green and brown propolis produced in Minas Gerais, Brazil was performed according to the methodology established by the Brazilian legislation. And, the content of 9 bioactive compounds in the samples was determined by RP-HPLC. GrProp showed a higher content of pinocembrin, artepillin C and baccharin, and a higher quantity of total flavonoids, in comparison with BrwProp. The mechanical mass content in both types of propolis was above the limit established by legislation. However, the other physicochemical parameters were within the limits. The chemical composition, especially the flavonoid content and the free radical (DPPH) scavenger property confer to both types of propolis a promising pharmacological activity.
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Própolis , Própolis/química , Brasil , Flavonoides/farmacología , Antioxidantes/farmacología , Antioxidantes/químicaRESUMEN
The health benefits of polyunsaturated fatty acids (PUFAs) have encouraged the search for rich sources of these compounds. However, the supply chain of PUFAs from animals and plants presents environmental concerns, such as water pollution, deforestation, animal exploitation and interference in the trophic chain. In this way, a viable alternative has been found in microbial sources, mainly in single cell oil (SCO) production by yeast and filamentous fungi. Mortierellaceae is a filamentous fungal family world-renowned for PUFA-producing strains. For example, Mortierella alpina can be highlighted due to be industrially applied to produce arachidonic acid (20:4 n6), an important component of infant supplement formulas. Thus, the state of the art of strategies to increase PUFAs production by Mortierellaceae strains is presented in this review. Firstly, we have discussed main phylogenetic and biochemical characteristics of these strains for lipid production. Next, strategies based on physiological manipulation, using different carbon and nitrogen sources, temperature, pH and cultivation methods, which can increase PUFA production by optimizing process parameters are presented. Furthermore, it is possible to use metabolic engineering tools, controlling the supply of NADPH and co-factors, and directing the activity of desaturases and elongase to the target PUFA. Thus, this review aims to discuss the functionality and applicability of each of these strategies, in order to support future research for PUFA production by Mortierellaceae species.
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Ácidos Grasos Insaturados , Mortierella , Animales , Filogenia , Ácidos Grasos Insaturados/metabolismo , Ingeniería Metabólica , Saccharomyces cerevisiae/metabolismo , Carbono/metabolismo , Mortierella/genética , Mortierella/química , Ácidos Grasos/metabolismoRESUMEN
Melanoma is the deadliest type of skin cancer, with about 61,000 deaths annually worldwide. Late diagnosis increases mortality rates due to melanoma's capacity to metastasise rapidly and patients' resistance to the available conventional therapies. Consequently, the interest in natural products as a strategy for drug discovery has been emerging. Propolis, a natural product produced by bees, has several biological properties, including anticancer effects. Propolis from Gerês is one of the most studied Portuguese propolis. Our group has previously demonstrated that an ethanol extract of Gerês propolis collected in 2018 (G18.EE) and its fractions (n-hexane, ethyl acetate, and n-butanol) decrease melanoma cell viability. Out of all the fractions, G18.EE-n-BuOH showed the highest potential as a melanoma pharmacological therapy. Thus, in this work, G18.EE-n-BuOH was fractioned into 17 subfractions whose effect was evaluated in A375 BRAF-mutated melanoma cells. The subfractions with the highest cytotoxic activity were analysed by UPLC-DAD-ESI/MSn in an attempt to understand which phenolic compounds could account for the anti-melanoma activity. The compounds identified are typical of the Gerês propolis, and some of them have already been linked with antitumor effectiveness. These results reaffirm that propolis compounds can be a source of new drugs and the isolation of compounds could allow its use in traditional medicine.