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BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is characterized by inattention, hyperactivity, and impulsivity and includes one of the most prevalent neurodevelopmental disorders in childhood. Despite the high prevalence, many professionals who work with children and adolescents with this disorder do not have enough knowledge on the subject. Physical education professionals deal directly with these children and need the knowledge to choose which skills and/or motor criteria to emphasize in their classes. However, issues related to neurodevelopmental disorders are not frequently addressed in the physical education courses, which impairs proper dealing with this population. AIM: This study aims to verify the level of knowledge about ADHD and its motor impairments in professionals and students of physical education. METHOD: A questionnaire was developed by researchers of motor behavior and was applied to professionals and students of physical education. The participants' responses were then analyzed through descriptive and inferential statistics. RESULTS: The results indicate that although the volunteers have basic notions about the subject, they do not have enough preparation to deal with children with ADHD. CONCLUSION: It was concluded that the knowledge about ADHD is insufficient and a reformulation in the curriculum of physical education courses is recommended.

BACKGROUND: The fronto-central slow-wave known as the contingent negative variation (CNV) is an electroencephalographic measure related to the ability of the motor system to extract spatial-temporal regularities to produce a motor response. AIM: This study aimed to investigate the levels of electrocortical activity prior to predictable and unpredictable stimuli in a motor control task, and the association between CNV and reaction time (RT). METHOD: Seventeen participants performed a task that consisted of removing the right index finger from the space bar as fast as possible after stimulus onset. All participants practiced under both a predictable (PC) and an unpredictable (UC) context. RESULTS: Results indicated that RT under the unpredictable context was slower than under the predictable context. However, CNV levels under predictable and unpredictable contexts did not differ. CONCLUSION: The certainty of stimulus appearance in the UC may have produced effects similar to those under the PC, resulting in similar CNV levels. However, the use of this mechanism under the UC was suboptimal to motor performance.

In 2020, the South African government adopted a controversial measure in response to the COVID-19 pandemic, a nationwide ban on the sale and transport of alcoholic drinks. In this article, we explore the process that led to the construction of alcohol consumption as a “public problem” in the country, highlighting connections between alcohol drinking, politics, the economy, public health, public safety, and social inequality. We observe how the 2020 alcohol ban was decided upon, justified and enforced, following a long history of government attempts to control alcohol consumption among poor non-White South Africans. Based on ethnographic data, we present some patterns and meanings of alcohol consumption in popular settings and provide a glimpse into the drinking practices of more affluent South Africans during the alcohol ban. In doing so, we intend to offer a broader portrait of the phenomenon, one that helps grasp this intricate issue. Resumo Em 2020, o governo sul-africano adotou uma medida polêmica em resposta à pandemia de COVID-19: a proibição nacional da venda e do transporte de bebidas alcoólicas. Neste artigo, exploramos o processo que levou à construção do consumo de álcool como um “problema público” no país, destacando as conexões entre consumo de álcool, política, economia, saúde pública, segurança pública e desigualdade social. Observamos como a proibição do álcool em 2020 foi decidida, justificada e aplicada, após uma longa história de tentativas do governo de controlar o consumo de álcool entre sul-africanos pobres não brancos. Com base em dados etnográficos, apresentamos alguns padrões e significados do consumo de álcool em ambientes populares e fornecemos um vislumbre das práticas de consumo de bebidas entre os sul-africanos mais ricos durante a proibição do álcool. Com isso, pretendemos oferecer um retrato mais amplo do fenômeno, que ajude a apreender essa intrincada questão.

Neste artigo, indicamos a inadequação do conceito de xenofobia para explicar a violência contra estrangeiros na África do Sul. Com as noções de “fetichização das origens” e “vandalismo”, alguns analistas sul-africanos caracterizaram violações aos direitos de imigrantes como distúrbios psiquiátricos e barbarismo, antigos clichês sobre a África. Mediante a etnografia dos Tshwane Riots (2016), indicamos que os saques de comerciantes Pakistani ocorreram conforme “leis” locais. Interpretamos esses ataques como estratégia política e sinal da existência de disputas soberanas entre o Congresso Nacional Africano (CNA) e setores orgânicos de seu eleitorado. In Xenophobia? Moral Economy, Ethical-Moral Rights, and Citizenship Dilemmas in South Africa, we argue the inadequacy of xenophobia to account for violence against foreigners in South Africa. With the notions of fetishising of origins and vandalism, scholars cast violations against the rights of immigrants as psychiatric disturbs and barbarism, clichés about Africa. Via the ethnography of the Tshwane Riots (2016), we show that the ransacking of Pakistani businesses in an informal settlement in Pretoria followed local laws. We interpret these attacks as a political strategy and a sovereign dispute between the African National Congress (ANC) and its organic constituency.

Ecotoxicological tools have proved to be sensitive and appropriate for the evaluation of the effectiveness of treatments used in wastewater treatment plants (WWTP). The objective of this study was to assess the applicability of bioassays and biomarkers to evaluate the efficiency of different treatments throughout WWTP samples[A—raw influent, B—preliminary effluent, C—final effluent, and D—receiving stream], seasonally over 1 year, through a multispecies approach: i) bacterial cell viability [Escherichia coli, Rhodopirellulla rubra, Arthrobacter sp., and Pseudomonas putida]; ii) microalgae Raphidocelis subcapitata and the macrophyte Lemna minor growth inhibition; and iii) microcrustacean Daphnia magna acute and feeding rate assays. Total chlorophyll, malondialdehyde, and proline levels were evaluated in L. minor, and catalase, glutathione-S-transferase activities, and thiobarbituric acid reactive substances levels were quantified in D. magna, after exposure to wastewater samples. Overall, the tested species showed different sensitivities, P. putida = Arthrobacter sp. = R. rubra R. subcapitata E. coli = D. magna = L. minor, to the collected samples. The results obtained in D. magna and L. minor assays demonstrated that these organisms can be used in programs for monitoring and environmental assessment of wastewater effluents. The present study demonstrates the usefulness of ecotoxicological tools, with multispecies and different endpoints, to assess the effectiveness of WWTPs. Moreover, it is important to ensure that WWTP implements a monitoring program to minimize the discharge of effluents that compromise the environment in order to guarantee the good ecological quality of the environmental ecosystems.

Background: The benefits of variable practice in motor learning have been traditionally explained by the increased demand for memory processes induced by trial-to-trial changes. Recently, a new perspective associating increased demand for perception with variable practice has emerged. Aim: This revision aims to present and discuss the findings in this exciting topic newly opened. Results / Interpretation: In the second half of 2010’s, a number of studies have pointed out differences in perceptual processing when compared variable and repetitive practices. Different levels of (a) hemodynamic activation, (b) electroencephalographic activity, (c) neurochemical activity, and (d) oculomotor behavior have provided evidence that perceptual processes are affected differently by variable and repetitive practices.

A formal swimming learning occurs through a direct interaction between teacher and learner. The aim of this study is to present models for classification of learning in stages and discuss their implications for the teaching-learning process of swimming. This narrative review was carried out through bibliographic research. We used qualitative and exploratory approaches. Models proposed by Adams (1971), Fitts and Posner, (1967), and Gentile (1972) categorize learning into several stages, accounting for the characteristics of the learners and the environment. To enhance the teaching-learning process of swimming skills, the teacher must recognize the stages in which the learner finds himself, and to establish efficient teaching strategies. The learning stage identification affects the manipulation of variables that interfere in learning, such as setting goals, selecting content, choosing appropriate strategies and assessing learning, regardless of the swimming stroke. Even though some points will differ between swimming styles, such as the specificity, the specificity of errors, the informational demand, and the amount of practice, it is the teacher's role to establish the relationship between the student and the contents to be taught in the teaching-learning process. Overall, the quality of the teaching-learning process will depend on the teacher’s ability to propose contents that are appropriate to the characteristics, needs and expectations of the learners, being sufficiently challenging to arouse motivation and to promote skills learning. El aprendizaje formal de la natación ocurre mediante una interacción directa entre maestro y alumno. El objetivo de este estudio fue presentar modelos de clasificación del aprendizaje en etapas y discutir sus implicaciones para el proceso de enseñanza-aprendizaje de la natación. Esta revisión narrativa se realizó a través de una investigación bibliográfica. Se utilizaron enfoques cualitativos y exploratorios. Los modelos propuestos por Adams (1971), Fitts y Posner, (1967) y Gentile (1972) clasifican el aprendizaje en varias etapas, teniendo en cuenta las características de los alumnos y del entorno. Para potencializar el proceso de enseñanza-aprendizaje de las habilidades de natación, el docente debe reconocer las etapas en las que se encuentra el aprendiz y establecer estrategias de enseñanza eficientes. La identificación de la etapa de aprendizaje afecta la manipulación de variables que interfieren en el aprendizaje, como el establecimiento de metas, la selección de contenidos, la elección de estrategias adecuadas y la evaluación del aprendizaje, independientemente del estilo de natación. Aunque algunos puntos diferirán entre los estilos de natación, como la especificidad y cantidad de información, la especificidad de los errores, la demanda de información y la cantidad de práctica, es el papel del profesor establecer la relación entre el estudiante y los contenidos a enseñarse en el proceso de enseñanza-aprendizaje. En general, la calidad del proceso de enseñanza-aprendizaje dependerá de la capacidad del profesor proponer contenidos adecuados a las características, necesidades y expectativas de los educandos, siendo lo suficientemente desafiantes para despertar la motivación y promover el aprendizaje de competencias. A aprendizagem formal da natação ocorre por meio da interação direta entre professor e aprendiz. O objetivo deste estudo foi apresentar modelos de classificação da aprendizagem em etapas e discutir suas implicações para o processo de ensino-aprendizagem da natação. Esta revisão narrativa foi realizada por meio de pesquisa bibliográfica. Para tanto, utilizaram-se abordagens qualitativas e exploratórias. Os modelos propostos por Adams (1971), Fitts & Posner, (1967) e Gentile (1972) categorizam a aprendizagem em vários estágios, considerando as características dos aprendizes e do ambiente. A fim de potencializar o processo de ensino-aprendizagem na natação, o professor deve reconhecer as etapas em que o aprendiz se encontra e estabelecer estratégias de ensino eficientes. A identificação do estágio de aprendizagem afeta a manipulação de variáveis ​​que influenciam na aprendizagem, como o estabelecimento de metas, a seleção dos conteúdos, a escolha das estratégias adequadas e a avaliação da aprendizagem, independentemente estilo do nado. Ainda que hajam diferenças entre os nados, como a especificidade, a especificidade dos erros, a demanda informacional e a quantidade de prática, é papel do professor estabelecer a relação entre o aluno e os conteúdos a serem ensinados no processo de ensino-aprendizagem. De forma geral, a qualidade do processo de ensino-aprendizagem dependerá da capacidade do professor para propor conteúdos adequados às características, necessidades e expectativas dos aprendizes, conteúdos suficientemente desafiadores para motivá-los e promover aprendizagem.

In the wild various organisms contribute to daphnids diet. This study, intendeds to evaluate the potential of the concentration ofFeeding assays were performed according to standard guidelines for chronic assays (21 days), and life-history parameters and several biomarkers (protein content, oxidative stress, energetic reserves and pigments) were measured. Five food regimens were conducted with 20 individual replicates (A -The five diets showed a different C, N, and carotenoids composition, with an increase in the mixed diets. The results confirmed that the mixed diets improvedResults demonstrated that different diets provided a nutritional diversified food to the daphnids that induced differences in

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).

The high salt concentration is the major factor limiting microbial growth at salterns, along with solar radiation, temperature, and pH. These environmental factors play key roles in the acquisition of unique genetic adaptations for the survival of microorganisms in salterns, which can result in the production of interesting secondary metabolites. The main goal of the present work was to isolate and compare the culturable microbiota from two geographically distant salterns in Portugal and access their biotechnological potential.Culturomics approaches using different culture media were applied for microbial isolation. All isolates were identified either by 16S rRNA or ITS genes sequencing, and their biotechonological potential was assessed by PCR.Overall, 154 microbial isolates were recovered that were phylogenetically assigned to 45 taxa from 9 different phyla. From these, 26 isolates may represent putative new taxa. The predominant genera obtained wereThis study adds up valuable knowledge on the culturable microbiota of Portuguese salterns and on its potential for production of secondary metabolites. In the long run, this study provides a widely diverse microbial collection for future works. Data public repository: All DNA sequences were deposited in the GenBank database at National Centre for Biotechnology Information (NCBI) web platform under accession numbers OK169439-OK169485, OK216020-OK216124, OK287059 and OK326927.

Aim This study aims to evaluate the effect of erbium: Yttrium–aluminum–garnet (Er:YAG) laser irradiation on the enamel microshear bond strength (µSBS), followed by the utilization of etch-and-rinse and universal adhesive systems. Materials and methods A total of 32 molars were sectioned in the mesiodistal direction producing 64 samples that were randomized into two groups (n = 32): single bond 2 (SB2) (etch-and-rinse system; 3M), SB universal (SBU) (universal etching system; The SB2 and SBU groups were then divided into two subgroups (n = 16): (i) enamel was irradiated with an Er:YAG laser (λ = 2.94 μm, 60 mJ, 10 Hz), and (ii) enamel served as a control. The samples were restored with TPH3 (Dentsply), stored in artificial saliva for 24 hours, and subjected to a microshear test. Results Kruskal–Wallis (p Conclusion The previous irradiation of enamel with Er:YAG laser does not interfere with the performance of simplified two-step etch-and-rinse and universal adhesive systems. Clinical significance The increasing use of Er:YAG laser is important to evaluate the influence of this irradiation on the adhesion of restorative materials. Thus, to obtain the longevity of the restorative procedures, it is necessary to know the result of the association of the present adhesive systems to the irradiated substrate. How to cite this article De Jesus Tavarez RR, Rodrigues LLC, Diniz AC, Lage LM, Torres CRG, Bandeca MC, Firoozmand LM. Does Erbium:Yttrium–Aluminum–Garnet Laser to Enamel improve the Performance of Etch-and-rinse and Universal Adhesives? J Contemp Dent Pract 2018;19(3):278-282.

In this study, we investigated the chemical compositions and antioxidant and antimicrobial activities of propolis produced by the stingless bee Frieseomelitta longipes and the honeybee Apis mellifera collected from colonies in North Brazil. In terms of volatile composition, both mono- and sesquiterpenes were detected in the propolis of F. longipes while only sesquiterpenes were detected in that of A. mellifera. Out of 50 volatiles identified in all samples, 26 were found exclusively in F. longipes propolis and 8 were found exclusively in A. mellifera propolis. The chemical profiles of the propolis extracts were determined by atmospheric pressure chemical ionization-mass spectrometry and liquid chromatography-electrospray ionization-tandem mass spectrometry allowed to identify several prenylated benzophenones. A. mellifera extracts exhibited major antioxidant activity as assessed by the 2,2-diphenyl-1-picrylhydrazyl method and all extracts exhibited antioxidant activity as assessed by the β-carotene/linoleic acid method. The ethanolic extracts of the propolis showed promisor activity against all tested microorganisms. Made available in DSpace on 2019-02-15T23:42:42Z (GMT). No. of bitstreams: 1 01004042qn41050485.pdf: 673911 bytes, checksum: 0fa612807ad27c5b53f14b66e2607183 (MD5) Previous issue date: 2019-02-14

The metastasis‐associated protein 1(MTA1)/histone deacetylase (HDAC) unit is a cancer progression‐related epigenetic regulator, which is overexpressed in hormone‐refractory and metastatic prostate cancer (PCa). In our previous studies, we found a significantly increased MTA1 expression in a prostate‐specific Pten‐null mouse model. We also demonstrated that stilbenes, namely resveratrol and pterostilbene (Pter), affect MTA1/HDAC signaling, including deacetylation of tumor suppressors p53 and PTEN. In this study, we examined whether inhibition of MTA1/HDAC using combination of Pter and a clinically approved HDAC inhibitor, SAHA (suberoylanilide hydroxamic acid, vorinostat), which also downregulates MTA1, could block prostate tumor progression in vivo. We generated and utilized a luciferase reporter in a prostate‐specific Pten‐null mouse model (Pb‐Cre +; Pten f/f; Rosa26 Luc/+) to evaluate the anticancer efficacy of Pter/SAHA combinatorial approach. Our data showed that Pter sensitized tumor cells to SAHA treatment resulting in inhibiting tumor growth and additional decline of tumor progression. These effects were dependent on the reduction of MTA1‐associated proangiogenic factors HIF‐1α, VEGF, and IL‐1β leading to decreased angiogenesis. In addition, treatment of PCa cell lines in vitro with combined Pter and low dose SAHA resulted in more potent inhibition of MTA1/HIF‐1α than by high dose SAHA alone. Our study provides preclinical evidence that Pter/SAHA combination treatment inhibits MTA1/HIF‐1α tumor‐promoting signaling in PCa. The beneficial outcome of combinatorial strategy using a natural agent and an approved drug for higher efficacy and less toxicity supports further development of MTA1‐targeted therapies in PCa.

We have previously shown that metastasis-associated protein 1 (MTA1), a chromatin remodeler, plays an important role in prostate cancer invasiveness, likely through regulation of epithelial-to-mesenchymal transition. Here, we identified miR-22 as an epigenetic-microRNA (Epi-miR) directly induced by MTA1 and predicted to target E-cadherin. Loss-of-function and overexpression studies of MTA1 reinforced its regulatory role in miR-22 expression. MiR-22 directly targets the 3'-untranslated region of E-cadherin, and ectopic overexpression of miR-22 diminishes E-cadherin expression. Overexpression of miR-22 in prostate cancer cells promotes cell invasiveness and migration. Meta-analysis of patient tumor samples indicates a positive correlation between MTA1 and miR-22, supporting their inhibitory effect on E-cadherin expression. Our findings implicate the MTA1/Epi-miR-22/E-cadherin axis as a new epigenetic signaling pathway that promotes tumor invasion in prostate cancer.

There is a strong need to develop new drugs against many severe diseases. Therapy resistance is a major problem, for instance, in infectious diseases and cancer. Drug discovery has again turned to nature to search for molecules that can become drug leads. Although many bacterial phyla are extensively studied, some, like the Planctomycetes, remain largely unexplored as potential sources of new leads. Planctomycetes form a diverse group of bacteria with peculiar characteristics such as division by polar budding and absence of the FtsZ gene. Furthermore, they exhibit large genomes up to 12.5 Mb, and possess a high number of secondary metabolites as assessed by in silico genomic analysis. These characteristics have also revealed the presence of potential anticancer activity. Based on these promising characteristics, we wanted to investigate Planctomycetes as a source for natural products with anticancer properties. Organic and aqueous extracts were obtained from cultivated Planctomycetes strains originated from a variety of habitats such as marine systems (free living or attached to marine algae), deep marine iron hydroxide deposits, brackish water and glacier ice system. The extracts were screened for ability to inhibit cell growth, or induce cell death on two cancer cell lines, the human prostatic cancer cell line PC3, and human acute myeloid leukaemia (AML) cell line MOLM-13, as well as normal rat kidney epithelial cell line (NRK). Out of 39 strains, five exhibited cytotoxicity toward NRK cells, whereas 32 of the strains were toxic to the AML cell line, and four were toxic to the PC3 cell line. Two strains showed high toxicity and selectivity toward both the cancer cell lines over the NRK-cells, and are potential producers of anti-cancer compounds. We found no correlation between bioactivity and strains habitat and geographic location but regarding phylogeny some Rhodopirellula spp. showed higher toxicity toward MOLM-13 cells. These results from the first anticancer screening with Planctomycetes showed that these peculiar microorganisms should be further explored for anti-cancer compounds, and that more effort must be put in providing culture collections for drug development purposes. publishedVersion

In the beginning of the twenty-first century, humanity faces great challenges regarding diseases and health-related quality of life. A drastic rise in bacterial antibiotic resistance, in the number of cancer patients, in the obesity epidemics and in chronic diseases due to life expectation extension are some of these challenges. The discovery of novel therapeutics is fundamental and it may come from underexplored environments, like marine habitats, and microbial origin. Actinobacteria are well-known as treasure chests for the discovery of novel natural compounds. In this study, eighteen Actinomycetales isolated from marine sponges of three Erylus genera collected in Portuguese waters were tested for bioactivities with the main goal of isolating and characterizing the responsible bioactive metabolites. The screening comprehended antimicrobial, anti-fungal, anti-parasitic, anti-cancer and anti-obesity properties. Fermentations of the selected strains were prepared using ten different culturing media. Several bioactivities against the fungus Aspergillus fumigatus, the bacteria Staphylococcus aureus methicillin-resistant (MRSA) and the human liver cancer cell line HepG2 were obtained in small volume cultures. Screening in higher volumes showed consistent anti-fungal activity by strain Dermacoccus sp. #91-17 and Micrococcus luteus Berg02-26. Gordonia sp. Berg02-22.2 showed anti-parasitic (Trypanosoma cruzi) and anti-cancer activity against several cell lines (melanoma A2058, liver HepG2, colon HT29, breast MCF7 and pancreatic MiaPaca). For the anti-obesity assay, Microbacterium foliorum #91-29 and #91-40 induced lipid reduction on the larvae of zebrafish (Danio rerio). Dereplication of the extracts from several bacteria showed the existence of a variety of secondary metabolites, with some undiscovered molecules. This work showed that Actinomycetales are indeed good candidates for drug discovery., This research was partially supported by the Strategic Funding UID/Multi/04423/2013 through national funds provided by FCT – Foundation for Science and Technology and European Regional Development Fund (ERDF), in the framework of the programme PT2020, the EU H2020-TWINN-2015, BLUEandGREEN – Boosting scientific excellence and innovation capacity in biorefineries based on marine resources (Project No. 692419) and the European ERA-NET Marine Biotechnology project CYANOBESITY (ERA-MBT/0001/2015), financed by national funds through FCT (Foundation for Science and Technology, Portugal). Ralph Urbatzka was supported by a FCT postdoc grant (SFRH/BPD/112287/2015). The MEDINA authors disclosed the receipt of financial support from Fundación MEDINA, a public–private partnership of Merck Sharp & Dohme de España S.A./Universidad de Granada/Junta de Andalucía. Moreover, some of the equipment used in this work was supported by the Ministerio de Ciencia e Innovación and the European Union (Grant INP-2011-0016-PCT-010000-ACT6).

[Objective] To identify factors related to a poor health-related and global quality of life (QoL) in a cohort of non-demented Parkinson's disease (PD) patients and compare to a control group., [Methods] The data correspond to the baseline evaluation of the COPPADIS-2015 Study, an observational, 5-year follow-up, multicenter, evaluation study. Three instruments were used to assess QoL: (1) the 39-item Parkinson's disease Questionnaire (PDQ-39), (2) a subjective rating of global QoL (PQ-10), and (3) the EUROHIS-QOL 8-item index (EUROHIS-QOL8). Multiple linear regression methods were used to evaluate the direct impact of different variables on these QoL measures., [Results] QoL was worse in PD patients (n = 692; 62.6 ± 8.9 years old, 60.3% males) than controls (n = 206; 61 ± 8.3 years old, 49.5% males): PDQ-39, 17.1 ± 13.5 vs 4.4 ± 6.3 (p, [Conclusions] QoL is worse in PD patients than in controls. Mood, non-motor symptoms burden, and gait problems seem to be the most relevant factors affecting health-related and global perceived QoL in non-demented PD patients.

Tobacco smoking is a leading preventable cause of premature death in the USA. Menthol is a significant flavoring additive in tobacco products. Clinical evidence suggests that menthol may promote tobacco smoking and nicotine dependence. However, it is unclear whether menthol enhances the reinforcing actions of nicotine and thus facilitates nicotine consumption. This study employed a rat model of nicotine self-administration to examine the effects of menthol on nicotine-taking behavior. Male Sprague-Dawley rats were trained in daily 1-h sessions to press a lever for intravenous nicotine self-administration under a fixed-ratio 5 schedule of reinforcement. In separate groups, rats self-administered nicotine at four different doses (0.0075, 0.015, 0.03, and 0.06 mg/kg/infusion). Five minutes prior to the two test sessions, menthol (5 mg/kg) or its vehicle was administered intraperitoneally in all rats in a counterbalanced design within each group. In separate rats that self-administered 0.015 mg/kg/infusion nicotine, menthol dose-response function was determined. Menthol was also tested on food self-administration. An inverted U-shaped nicotine dose-response curve was observed. Menthol pretreatment shifted the nicotine dose-response curve to the left. The facilitating effect of menthol on the self-administration of 0.015 mg/kg/infusion nicotine was dose-dependent, whereas it produced similar effects at doses above the threshold of 2.5 mg/kg. Menthol tended to suppress the self-administration of food pellets. These data demonstrate that menthol enhances the reinforcing effects of nicotine, and the effect of menthol was specific to nicotine. The findings suggest that menthol directly facilitates nicotine consumption, thereby contributing to tobacco smoking.

Overexpression of the epigenetic modifier metastasis-associated protein 1 (MTA1) is associated with aggressive human prostate cancer. The purpose of this study was to determine MTA1- targeted chemopreventive and therapeutic efficacy of pterostilbene, a natural potent analog of resveratrol, in pre-clinical models of prostate cancer. Here, we show that high levels of MTA1 expression in Pten-loss prostate cooperate with key oncogenes, including c-Myc and Akt among others, to promote prostate cancer progression. Loss-of-function studies using human prostate cancer cells indicated direct involvement of MTA1 in inducing inflammation and epithelial-to-mesenchymal transition. Importantly, pharmacological inhibition of MTA1 by pterostilbene resulted in decreased proliferation and angiogenesis and increased apoptosis. This restrained prostatic intraepithelial neoplasia (PIN) formation in prostate-specific Pten heterozygous mice and reduced tumor development and progression in prostate-specific Pten-null mice. Our findings highlight MTA1 as a key upstream regulator of prostate tumorigenesis and cancer progression. More significantly, it offers pre-clinical proof for pterostilbene as a promising lead natural agent for MTA1-targeted chemopreventive and therapeutic strategy to curb prostate cancer.

In the beginning of the twenty-first century, humanity faces great challenges regarding diseases and health-related quality of life. A drastic rise in bacterial antibiotic resistance, in the number of cancer patients, in the obesity epidemics and in chronic diseases due to life expectation extension are some of these challenges. The discovery of novel therapeutics is fundamental and it may come from underexplored environments, like marine habitats, and microbial origin. Actinobacteria are well-known as treasure chests for the discovery of novel natural compounds. In this study, eighteen Actinomycetales isolated from marine sponges of three Erylus genera collected in Portuguese waters were tested for bioactivities with the main goal of isolating and characterizing the responsible bioactive metabolites. The screening comprehended antimicrobial, anti-fungal, anti-parasitic, anti-cancer and anti-obesity properties. Fermentations of the selected strains were prepared using ten different culturing media. Several bioactivities against the fungus Aspergillus fumigatus, the bacteria Staphylococcus aureus methicillin-resistant (MRSA) and the human liver cancer cell line HepG2 were obtained in small volume cultures. Screening in higher volumes showed consistent anti-fungal activity by strain Dermacoccus sp. #91-17 and Micrococcus luteus Berg02-26. Gordonia sp. Berg02-22.2 showed anti-parasitic (Trypanosoma cruzi) and anti-cancer activity against several cell lines (melanoma A2058, liver HepG2, colon HT29, breast MCF7 and pancreatic MiaPaca). For the anti-obesity assay, Microbacterium foliorum #91-29 and #91-40 induced lipid reduction on the larvae of zebrafish (Danio rerio). Dereplication of the extracts from several bacteria showed the existence of a variety of secondary metabolites, with some undiscovered molecules. This work showed that Actinomycetales are indeed good candidates for drug discovery.

This study aims to evaluate the effect of erbium: Yttrium-aluminum-garnet (Er:YAG) laser irradiation on the enamel microshear bond strength (μSBS), followed by the utilization of etch-and-rinse and universal adhesive systems.A total of 32 molars were sectioned in the mesiodistal direction producing 64 samples that were randomized into two groups (n = 32): single bond 2 (SB2) (etch-and-rinse system; 3M), SB universal (SBU) (universal etching system; The SB2 and SBU groups were then divided into two subgroups (n = 16): (i) enamel was irradiated with an Er:YAG laser (λ = 2.94 μm, 60 mJ, 10 Hz), and (ii) enamel served as a control. The samples were restored with TPH3 (Dentsply), stored in artificial saliva for 24 hours, and subjected to a micro-shear test.Kruskal-Wallis (p0.05) and Mann-Whitney U tests indicated no significant differences in uSBS between the groups, and the fractures were predominately at the resin-enamel interface.The previous irradiation of enamel with Er:YAG laser does not interfere with the performance of simplified two-step etch-and-rinse and universal adhesive systems.The increasing use of Er:YAG laser is important to evaluate the influence of this irradiation on the adhesion of restorative materials. Thus, to obtain the longevity of the restorative procedures, it is necessary to know the result of the association of the present adhesive systems to the irradiated substrate.

Aims Five sphingosine-1-phosphate receptors (S1PR): S1PR1, S1PR2, S1PR3, S1PR4 and S1PR5 (S1PR1–5) have been shown to be involved in the proliferation and progression of various cancers. However, none of the S1PRs have been systemically investigated. In this study, we performed immunohistochemistry (IHC) for S1PR1–S1PR5 on different tissues, in order to simultaneously determine the systemic distribution, subcellular localization and expression level of all five S1PRs. Methods We constructed tissue microarrays (TMAs) from 384 formalin-fixed paraffin-embedded (FFPE) blocks containing 183 benign and 201 malignant tissues from 34 human organs/systems. Then we performed IHC for all five S1PRs simultaneously on these TMA slides. The distribution, subcellular localization and expression of each S1PR were determined for each tissue. The data in benign and malignant tissues from the same organ/tissue were then compared using the Student's t-test. In order to reconfirm the subcellular localization of each S1PR as determined by IHC, immunocytochemistry (ICC) was performed on several malignant cell lines. Results We found that all five S1PRs are widely distributed in multiple human organs/systems. All S1PRs are expressed in both the cytoplasm and nucleus, except S1PR3, whose IHC signals are only seen in the nucleus. Interestingly, the S1PRs are rarely expressed on cellular membranes. Each S1PR is unique in its organ distribution, subcellular localization and expression level in benign and malignant tissues. Among the five S1PRs, S1PR5 has the highest expression level (in either the nucleus or cytoplasm), with S1PR1, 3, 2 and 4 following in descending order. Strong nuclear expression was seen for S1PR1, S1PR3 and S1PR5, whereas S1PR2 and S1PR4 show only weak staining. Four organs/tissues (adrenal gland, liver, brain and colon) show significant differences in IHC scores for the multiple S1PRs (nuclear and/or cytoplasmic), nine (stomach, lymphoid tissues, lung, ovary, cervix, pancreas, skin, soft tissues and uterus) show differences for only one S1PR (cytoplasmic or nuclear), and twenty three organs/tissues show no significant difference in IHC scores for any S1PR (cytoplasmic or nuclear) between benign and malignant changes. Conclusion This is the first study to evaluate the expression level of all S1PRs in benign and malignant tissues from multiple human organs. This study provides data regarding the systemic distribution, subcellular localization and differences in expression of all five S1PRs in benign and malignant changes for each organ/tissue.

Background Abdominal perineal excision (APE) was originally described with levator ani removal for rectal cancer. An even wider, more aggressive extralevator resection for APE has been proposed. Although some surgeons are performing a very wide ‘extralevator APE (ELAPE)’, there are few data to recommend it routinely. This multicentre study aimed to compare outcomes of APE and ELAPE. Methods A multicentre propensity case-matched analysis comparing two surgical approaches (APE and ELAPE) was performed. All patients who underwent abdominoperineal resection of a rectal tumour were considered for the analysis. Tumour height was defined by magnetic resonance imaging measurement and patients with stage II–III tumours had neoadjuvant radiochemotherapy. Involvement of the circumferential resection margin (CRM) and intraoperative tumour perforation were the main outcome measures. A logistic regression model was used to study the relationship between the surgical approaches and outcomes. Results From January 2008 to March 2013 a total of 1909 consecutive patients underwent APE or ELAPE, of whom 914 matched patients (457 in each group) formed the cohort for analysis. Intraoperative tumour perforation occurred in 7·9 and 7·7 per cent of patients during APE and ELAPE respectively (P = 0·902), and there was CRM involvement in 13·1 and 13·6 per cent (P = 0·846). There were no differences between APE and ELAPE in terms of postoperative complication rates (52·3 versus 48·1 per cent; P = 0·209), need for reoperation (7·7 versus 7·0 per cent; P = 0·703), perineal wound problems (26·0 versus 21·9 per cent; P = 0·141), mortality rate (2·0 versus 2·0 per cent; P = 1·000) and local recurrence rate at 2 years (2·7 versus 5·6 per cent; P = 0·664). Conclusion ELAPE does not improve rates of CRM involvement, intraoperative tumour perforation, local recurrence or mortality.

ObjectiveAbnormal ghrelin regulation may influence the development of obesity-associated conditions including polycystic ovary syndrome (PCOS). Our aim was to compare ghrelin regulation between PCOS cases and controls.DesignWe compared serum ghrelin (total) levels, fasting and 30-min post-oral (75 g) glucose load, between 50 PCOS cases and 28 female controls, including 22 body mass index (BMI)/fat mass-matched pairs. All subjects were of UK British/Irish origin.MethodsMeasurements included serum ghrelin (RIA technique (LINCO Research, St Charles MO, USA)), fat mass, serum testosterone, fasting serum insulin and plasma glucose levels. Insulin sensitivity was calculated as the homeostasis model assessment of insulin resistance (HOMA2 IR).ResultsFasting serum ghrelin levels were significantly lower in PCOS cases versus BMI/fat mass-matched controls (geometric mean (s.d. range), 1104 pg/ml (764–1595) vs 1756 pg/ml (1314–2347) respectively; P=2.3×10−4). Ghrelin suppression following oral glucose load was significantly blunted in PCOS cases versus BMI/fat mass-matched controls (geometric mean ghrelin suppression (s.d. range), 160 pg/ml (88–289) vs 424 pg/ml (220–818) respectively; P=2.0×10−4). Whole-group comparisons (50 PCOS cases versus 28 controls) adjusted for fat mass and age revealed similar results. In PCOS cases, there was a significant negative correlation between fasting serum ghrelin and HOMA2 IR (r2=−0.40, P=5.7×10−3). Following adjustment for HOMA2 IR, fat mass and age, comparisons between the whole groups of PCOS cases and controls revealed attenuated but significant differences in fasting serum ghrelin (P=1.3×10−3) and ghrelin suppression (P=1.8×10−3).ConclusionsIn women with PCOS, serum ghrelin levels are suppressed, showing a negative relationship with HOMA2 IR and a blunted response to oral glucose.

Introdução: Uropatias obstrutivas estão entre as principais doenças que acometem o feto. O diagnóstico precoce destas doenças permite estabelecer a terapêutica adequada, visando minimizar os riscos de danos à função renal no nascimento. Os marcadores bioquímicos têm sido utilizados na predição do prognóstico da função renal em fetos. A uromodulina, também chamada de proteína de Tamm-Horsfall (THP), é produzida exclusivamente nos rins, e em condições normais, é a proteína excretada em maior volume na urina humana. Ela desempenha importantes funções nos rins e trato urinário. Participa dos processos de transporte de íons, interage com vários componentes do sistema imunológico e possui papel na defesa contra infecções do trato urinário. Além disso, se mostrou um bom biomarcador de função renal em adultos portadores de diversas doenças renais. Objetivos: Avaliar se a uromodulina é produzida e eliminada pelos rins durante a vida fetal através da análise de urina fetal e líquido amniótico, além de estabelecer correlação com o parâmetro bioquímico de função renal já utilizado no Centro de Medicina Fetal do Hospital das Clínicas da UFMG (CEMEFE/HC). Métodos: Entre 2013 e 2015, foram selecionados 29 fetos com indicação de exames invasivos para diagnóstico fetal em acompanhamento no CEMEFE/HC. Resultados: A dosagem da uromodulina foi possível e quantificável em todas as amostras e mostrou correlação significativa com a osmolaridade. Conclusão: A uromodulina mostrou uma tendência em apresentar valores reduzidos em fetos com grave comprometimento renal no pré-natal. Assim, valores elevados desta proteína em dosagens de urina fetal ou líquido amniótico podem significar uma função renal preservada. Introduction: Obstructive uropathies are main diseases affecting the fetus. Early diagnosis allows to establish the appropriate therapy to minimize the risk of damage to kidney function at birth. Biochemical markers have been used to predict the prognosis of renal function in fetuses. Uromodulin, also known by Tamm-Horsfall protein (THP) is exclusively produced in the kidneys and in normal conditions is the protein excreted in larger amounts in human urine. It plays important roles in kidneys and urinary tract. Also it participates in ion transport processes, interact with various components of the immune system and has a role in defense against urinary tract infections. Moreover, this protein was proved to be a good marker of renal function in adult patients with several renal diseases. Objective: To evaluate if uromodulin is produced and eliminated by the kidneys during fetal life by analyzing fetal urine and amniotic fluid and to establish correlation with biochemical parameter of renal function already used in Fetal Medicine Center at the Clinic Hospital of UFMG (CEMEFE/HC). Methods: Between 2013 and 2015, were selected 29 fetuses with indication of invasive tests for fetal diagnosis in monitoring at the CEMEFE/HC. Results: The determination of uromodulin was possible and measurable in all samples and showed statistically significant correlation with the osmolarity. Conclusion: There was a tendency of lower levels of Uromodulin values in fetuses with severe renal impairment prenatally. Thus, high levels of this protein in fetal amniotic fluid or fetal urine dosages possibly mean kidney function preserved.

ResumenPaciente femenina, de 36 años de edad, con antecedentes de dos gestaciones, dos partos y ningún aborto, que en el año 2003 tras su segundo parto, distócico por cesárea, desarrolla una pericarditis de causa no precisada que produjo un derrame pericárdico grave con signos de taponamiento cardíaco, y requirió ingreso hospitalario y pericardiocentesis. Siete años después se identifican, en la consulta de Cardiología, síntomas clínicos de una pericarditis constrictiva, corroborada por ecocardiograma y cateterismo derecho; actualmente ingresa para pericardiectomía, evaluada como alto riesgo quirúrgico. / Abstract36 year-old female patient, with a history of two pregnancies, two births and no abortion, who in 2003 after her second delivery (cesarean for dystocia) she developed pericarditis of undetermined cause that produced a severe pericardial effusion with signs of cardiac tamponade and required hospital admission and pericardiocentesis. Seven years later, in the Cardiology service, clinical symptoms of constrictive pericarditis are identified and confirmed by echocardiography and right heart catheterization. This patient has been recently admitted for pericardiectomy, and evaluated as high surgical risk.

Little is known about the role of the attentional, motor and non-planning impulsivities in motor timing tasks. The aim of this study was to correlate the motor performance in a motor timing task with the performance in neuropsychological tests of twenty two volunteers. Before the execution of the motor task, participant wore a headphone and heard five times each temporal reference (2,500 and 3,500 msec) that consisted of two “bips”. After, the motor timing task was performed in five trials of each temporal reference. The task consisted in transporting tennis balls in a pre-defined sequence in each criterion time. It was evaluated: reaction time, movement time, constant error and absolute error. The neuropsychological tests IGT and CPT-II were applied to the evaluation of impulsivities. The findings indicated that attentional impulsivity was more related to the motor performance than the motor and non- planning impulsivities.