Aminoguanidine is a drug that prevents the formation of AGEs by reacting with initial glycation products and is effective in improving proteinuria and vessel elasticity, preventing diabetic retinopathy, and treating patients with diabetic nephropathy. Structural modifications of this molecule were carried out, and 19 derivatives were studied to present a potential hypoglycemic and antiglicante effect, preventing such complications for diabetics. For this purpose, an in vitro cytotoxicity test was initially carried out by colorimetric assay with MTT [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium], in macrophages of the J774 lineage. The AGEs were produced in vitro from the junction of glucose with bovine serum albumin and tested for evaluation of the antiglicante activity with reading in a fluorescence spectrophotometer. Derivatives with the best in vitro response were submitted to in vivo acute toxicity tests with Wistar rats and later evaluation of their antidiabetic and antiglycant potential in rats with streptozotocin-induced diabetes. After euthanasia, the heart, kidney, liver, and pancreas were removed for histopathological examination, and the blood for blood count and glycated hemoglobin, glucose, insulin, triglycerides, total cholesterol, HDL cholesterol, serum albumin, fructosamine, TGO, TGP, and GGT were collected. It is possible to conclude that the studied derivatives have the potential for the production of a drug that can be produced with them or associated with them and that is capable of reducing the glycemic indices and, at the same time, having an antiglicant action protecting individuals from macro- and microvascular complications.

Marine organisms represent a potential source of secondary metabolites with various therapeutic properties. However, the pharmaceutical industry still needs to explore the algological resource. The species Caulerpa lamouroux Forssk presents confirmed biological activities associated with its major compound caulerpin, such as antinociceptive, spasmolytic, antiviral, antimicrobial, insecticidal, and cytotoxic. Considering that caulerpin is still limited, such as low solubility or chemical instability, it was subjected to a structural modifications test to establish which molecular regions could accept structural modification and to elucidate the cytotoxic bioactive structure in Vero cells (African green monkey kidney cells, Cercopithecus aethiops; ATCC, Manassas, VA, USA) and antiviral to Herpes simplex virus type 1. Substitution reactions in the N-indolic position with mono- and di-substituted alkyl, benzyl, allyl, propargyl, and ethyl acetate groups were performed, in addition to conversion to their acidic derivatives. The obtained analogs were submitted to cytotoxicity and antiviral activity screening against Herpes simplex virus type 1 by the tetrazolium microculture method. From the semi-synthesis, 14 analogs were obtained, and 12 are new. The cytotoxicity assay showed that caulerpin acid and N-ethyl-substituted acid presented cytotoxic concentrations referring to 50% of the maximum effect of 1035.0 µM and 1004.0 µM, respectively, values significantly higher than caulerpin. The antiviral screening of the analogs revealed that the N-substituted acids with methyl and ethyl groups inhibited Herpes simplex virus type 1-induced cytotoxicity by levels similar to the positive control acyclovir.

Rótulos de alimentos desempenham importante função, pois por meio deles os consumidores obtêm acesso às informações dos alimentos. Este estudo objetivou avaliar informações de rotulagem de kombuchas produzidas no Brasil e sua adequação às normas de rotulagem de alimentos. Tratou-se de estudo transversal-descritivo, realizado entre julho e agosto de 2020. Foram analisadas 30 kombuchas de marcas diferentes. Foram coletadas informações referentes à denominação de venda, identificação de origem, conteúdo líquido, informação nutricional, lista de ingredientes, informação sobre presença de glúten, graduação alcoólica, alegações nutricionais e de propriedade funcional/saúde, presença de expressões proibidas na rotulagem de kombucha e avaliadas a conformidade de tais informações com as legislações de rotulagem. Nenhum dos produtos atendeu a todas as normas vigentes. As informações de rotulagem mais frequentes entre os produtos avaliados foram: denominação de venda (100%), veiculação de expressões proibidas (93,3%), conteúdo líquido (90%) e alegações funcionais (56,7%). Dentre as informações disponíveis nos rótulos, as que apresentaram mais inconformidades com as legislações foram: alegações funcionais (100%), utilização de expressões proibidas (100%), conteúdo líquido (96,3%), e denominação de venda (76,7%). Apesar da obrigatoriedade da maioria das informações analisadas, todas as bebidas apresentaram inconformidades em seus rótulos, nos parâmetros avaliados. Este achado aponta para a necessidade de fiscalização mais rigorosa, a fim de garantir informações corretas e confiáveis aos consumidores.

This article examines the most significant sources of innovation funding available to Poland. It is also intended to address the barriers to becoming a more innovative economy faced by the country under study. As is widely accepted, innovation is a critical component of any country's economic development and competitiveness in today's world. However, there are countries in the European Union (EU) that, despite their overall development, have lower innovation rates than the European average.

Obstructive sleep apnea (OSA) is associated with an increased susceptibility to multiple diseases. Identification of dysregulated microRNAs (miRs) and target genes in the context of OSA may provide relevant insights into OSA pathophysiology. We mined existing literature on dysregulated miRs in OSA studies to construct a database that allowed the exploration of associated biological processes and biomarkers. The search included all human observational studies that reported differentially expressed (DE) miRs, validated by quantitative PCR, in comparison with a control group (no OSA). DE miRs and target genes were further explored based on miR databases. Enrichment analyses were performed in R software using clusterProfiler and DOSE packages to discriminate associated pathways, namely biological processes (BP) and KEGG (Kioto Encyclopedia of Genes and Genomes) pathways. From 10 studies that met the inclusion criteria, we gathered 15 DE miRs in patients with OSA relative to control subjects, [13 down- and 2 up-regulated (p < 0.05)]. We found 12169 associated unique target genes. Pathway analysis of target genes revealed an enrichment in metabolic processes, related with catabolic processes, cell cycle, growth (top 10 biological processes with higher Gene ratio, q-value < 1x10-16). KEGG analysis showed that target genes were mostly associated with pathways of neurodegeneration, infection, and cancer (top 10 biological processes with higher Gene ratio, q-value < 1x10-4). Our results suggest an evident impact of OSA on miRs and gene expression that may be further explored as potential biomarkers for OSA. Gene targets and associated biological pathways emphasize the potential contribution of OSA to disease mechanisms and common comorbidities.

Universities are committed to preparing students to think creatively and entrepreneurially. According to Pinto, a university is a place of professional education that promotes the articulation of more effective pedagogical alternatives, the integration of theory and practice, and the resolution of real-world problems through the generation of critical and reflective actions informed by concrete experiences. Educational innovation influences the transformation of methodologies, instructional methods, and students' learned skills. Combining innovation and learning increases public awareness of this issue. This chapter aims to determine whether innovation is incorporated into teaching, whether it is incorporated into course planning, what is the students' perception of it, and the differences between cultures – taking into consideration higher education institutions from Portugal and Poland.

BACKGROUND:Obstructive Sleep Apnea (OSA) has been recognized as a major health concern worldwide, given its increasing prevalence, difficulties in diagnosis and treatment, and impact on health, economy, and society. Clinical guidelines highlight the need of biomarkers to guide OSA clinical decision-making, but so far, without success. In this systematic review and meta-analysis, registered on the International Prospective Register of Systematic Reviews database (ID CRD42020132556), we proposed to gather and further explore candidates identified in the literature as potential OSA biomarkers.METHODS:Search strategies for eight different databases (PubMed/Medline, Cochrane Library, Biblioteca Virtual da Saúde, Web of Science, EMBASE, World Intellectual Property Organization database, and bioRxiV and medRxiV Preprint Servers) were developed. We identified studies exploring potential biomarkers of OSA, in peripheral samples of adults, with and without OSA, with no comorbidities defined in study inclusion criteria, published after the last systematic review and meta-analysis conducted on OSA biomarkers, until May 31st, 2020. Risk of bias was assessed through the 14-item Quality Assessment Tool for Diagnostic Accuracy Studies. Demographic, clinical, and candidate biomarkers' data were collected and analyzed via random effects meta-analyses.FINDINGS:Among the 1512 unique studies screened, 120 met the inclusion criteria and 16 studies with low risk of bias were selected for meta-analyses. The selected 16 studies enrolled a total of 2156 participants, from which 1369 were diagnosed with OSA and 787 were disease-free controls. The assessed variables showed high heterogeneity. From the 38 biomarker candidates evaluated, only two were evaluated in more than one study. Most studies pinpointed candidates with more potential for OSA prognosis. ADAM29, FLRT2 and SLC18A3 mRNA levels in PBMCs, Endocan and YKL-40 levels in serum, and IL-6 and Vimentin levels in plasma revealed the most promising candidates for OSA diagnosis.INTERPRETATION:Although the current systematic review and meta-analysis allowed us to identify candidates to further explore as potential biomarkers in future studies, it is evident that OSA biomarkers research is still at an early stage. Most findings derive from small-size single-center study cohorts and single-candidate studies. We point several gaps in current OSA biomarker research that may guide into new directions and approaches towards the identification of OSA biomarkers.

Leishmaniasis is a neglected disease that affects millions of people, mostly in developing countries. Although this disease has a high impact on public health, there are few drug options to treat the different leishmaniasis forms. Additionally, these current therapies have various adverse effects, including gastrointestinal disturbances, headache, pancreatitis, and hepatotoxicity. Thus, it is essential to develop new drug prototypes to treat leishmaniasis. Accordingly, the present study aimed to evaluate the leishmanicidal activity of Morita-Baylis–Hillman adducts and their O-acetylates, carboxylic acid derivatives, and acid and ester derivatives of 2-methyl-phenylpropanoids against Leishmania chagasi. Initially, we evaluated the cytotoxicity of 16 derivatives (1-16G) against J774A.1 macrophages. Eight derivatives (2G, 4G, 5G, 7G, 9G, 10G, 13G, and 15G) showed no cytotoxicity at up to the maximum concentration tested (100 μM). When evaluated for antileishmanial effect against promastigote forms, 1G, 6G, 8G, 10G, 11G, 13G, 14G, 15G, and 16G displayed significant toxicity compared to the control (0.1% DMSO). Additionally, the compounds 1G, 5G, 7G, 9G, 11G, 13G, 14G, and 16G reduced macrophage infection by amastigotes. Thus, we conclude that these derivatives have antileishmanial effects, particularly 1G, which showed activity against promastigotes and amastigotes, and low toxicity against macrophages.

This study was intended to evaluate the creativity perception in the context of higher education by analyzing its different sub-components: - activities during classes; - students’ involvement during the classes; - evaluation of the degree of creativity in the classroom; and - the creativity understanding. The researchers designed a questionnaire to understand the different insights of students related to creativity. The study was focused on two target groups: - 1 st: students from Vilnius University of Applied Sciences - Group 2: students from Porto Accounting and Business School. For a better analysis and evaluation of the results obtained in the questionnaire, the Lewis Model was used to understand in which cultural categories the countries under study would be inserted and its impact on creativity. The statistical analysis results demonstrate that Lithuanian students show higher average results in the different sub-components of perceived creativity in higher education. However, the results indicate that the view of the concept understanding is close between Portuguese and Lithuanian students. The research that is presented in this paper is the first research related to creativity in education comparing Portugal and Lithuania and it could be a good base for further research of two economically similar yet culturally different countries

Introduction: Aging has been considered a risk factor for Obstructive Sleep Apnea (OSA) development. Untreated OSA has been associated with alterations that resemble the typical physiological and functional decline observed along the aging process. Aim: Evaluate how OSA might aggravate/promote aging through alteration in mitochondrial bioenergetics in OSA patients’ peripheral blood cells and to assess the impact of OSA treatment. Methods: A cohort of 17 OSA adult male patients was followed from the moment of their diagnosis (polysomnography), up to 4 months and 24 months of treatment with continuous positive airway pressure (CPAP) and compared with healthy subjects (age-matched and young controls). Results: OSA patients’ blood samples show decreased levels of mRNA/ protein mitochondrial fusion markers (p<0.01), a decreased tendency in mitochondrial complexes associated subunits expression and mitochondrial biogenesis impairment (p=0.08) in comparison with healthy control subjects, an effect that does not ameliorate after 24 months treatment. In addition, circulating levels of C-reactive protein (CRP) shows disruptions in OSA patients’ serum levels that are partially reverted upon OSA treatment. Conclusion: OSA aggravates/promotes dysfunctional mitochondria alterations and an inflammatory process, which can contribute to aging and directly impact on cellular signalling and inter organelle crosstalk. Most of these alterations are not reverted upon CPAP treatment, reinforcing the urgent need of new approaches for OSA diagnosis and treatment.

BackgroundObstructive Sleep Apnea (OSA) is a highly prevalent and underdiagnosed sleep disorder. Recent studies suggest that OSA might disrupt the biological clock, potentially causing or worsening OSA-associated comorbidities. However, the effect of OSA treatment on clock disruption is not fully understood.MethodsThe impact of OSA and short- (four months) and long-term (two years) OSA treatment, with Continuous Positive Airway Pressure (CPAP), on the biological clock was investigated at four time points within 24 h, in OSA patients relative to controls subjects (no OSA) of the same sex and age group, in a case-control study. Plasma melatonin and cortisol, body temperature and the expression levels and rhythmicity of eleven clock genes in peripheral blood mononuclear cells (PBMCs) were assessed. Additional computational tools were used for a detailed data analysis.FindingsOSA impacts on clock outputs and on the expression of several clock genes in PBMCs. Neither short- nor long-term treatment fully reverted OSA-induced alterations in the expression of clock genes. However, long-term treatment was able to re-establish levels of plasma melatonin and cortisol and body temperature. Machine learning methods could discriminate controls from untreated OSA patients. Following long-term treatment, the distinction between controls and patients disappeared, suggesting a closer similarity of the phenotypes.InterpretationOSA alters biological clock-related characteristics that differentially respond to short- and long-term CPAP treatment. Long-term CPAP was more efficient in counteracting OSA impact on the clock, but the obtained results suggest that it is not fully effective. A better understanding of the impact of OSA and OSA treatment on the clock may open new avenues to OSA diagnosis, monitoring and treatment.

Sustainable entrepreneurship pursues a triple agenda approximate economic, social, and ecological aspirations. We can agree upon the fact that environmental awareness is becoming more and more important on the global market and among people in general. Companies all over the world, have a bigger awareness, addressing more ecological concerns on their products, in order to become greener for consumers. This makes sustainable entrepreneurship an important topic in society and for the economy in general. This article is about sustainable entrepreneurship and the barriers that are connected to it, along with the comparison of two European Union countries, Portugal, and Slovenia, regarding the perceived obstacles and risk for starting a sustainable business. For this, we did use quantitative data from Eurobarometer with the intention to measure how much weight the upcoming entrepreneurship put on the conservation of nature and how much they think about environmental sustainability. We obtained the data that show the level of importance of ecology in business for the entrepreneurs in Portugal, for the ones in Slovenia, and in this case, we can also compare the data with the European Union average.

Introduction: Obstructive Sleep Apnea (OSA), one of the most common sleep disorders worldwide has been suggested to promote aging by inducing cellular and molecular aging mechanisms (Gaspar, et al. 2017). Understanding OSA putative effect on aging might contribute to understand new strategies to improve OSA diagnosis and treatment but also to counteract aging. Aim: To investigate cellular senescence and senescent associate secretory phenotype (SASP), a hallmark of aging, in OSA patients and the impact of OSA treatment. Methods: A cohort of 9 adult male patients diagnosed with severe OSA was followed from the moment of diagnosis with polysomnography (PSG), up to 4 months and 24 months of treatment with continuous pressure positive mask (CPAP). SASP biomarkers were evaluated in OSA patients in comparison to age-matched controls and younger controls, both validated by PSG. Results: OSA patients show a deregulation of pro- and anti-inflammatory cytokine levels, in comparison with age-matched and young controls, an effect that is no longer observed after treatment. In addition, OSA patients show alterations in extracellular vesicles release that are not fully re-established upon CPAP treatment. Conclusion: These results suggest that OSA might induce SASP. CPAP treatment might partially re-stablish some alterations. Hence, OSA early diagnosis and specific treatment may constitute a new strategy to delay ageing.