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Clinical research is the cornerstone of improvements in cancer care. However, it has been conducted predominantly in high-income countries with few clinical trials available in Brazil and other low-and-middle-income countries (LMIC). Of note, less than one-third of registered clinical trials addressing some of the most commonly diagnosed cancers (breast, lung and cervical) recruited patients from LMIC in the last years. The Institute Project CURA promoted the fourth CURA meeting, discussing barriers to cancer clinical research and proposing potential solutions. A meeting was held in São Paulo, Brazil, in June 2023 with representatives from different sectors: Brazilian Health Regulatory Agency (Anvisa), National Commission of Ethics in Research (CONEP), non-governmental organisations, such as the Latin American Cooperative Oncology Group, the Brazilian Society of Clinical Oncology (SBOC), Contract Research Organisations, pharmaceutical companies and investigators. A total of 16 experts pointed out achievements as shortening the time of regulatory processes involving Anvisa and CONEP, development of staff training programs, maintenance of the National Program of Oncological Attention (PRONON), and the foundation of qualified centres in North and Northeast Brazilian regions. Participants also highlighted the need to be more competitive in the field, which requires optimising ongoing policies and implementing new strategies as decentralisation of clinical research centres, public awareness campaigns, community-centered approaches, collaborations and partnerships, expansion of physicians-directed policies, exploring the role of the steering committee. Active and consistent reporting of the initiatives might help to propagate ongoing advances, increasing Brazilian participation in clinical cancer research. Engagement of all players is crucial to maintain continuous progress with further improvements in critical points including regulatory timelines and increments in qualified human resources which aligned with new educational initiatives focused on physicians and the general population will expand access to cancer clinical trials in Brazil.

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Hypothalamic inflammation and metabolic changes resulting from the consumption of high-fat diets have been linked to low grade inflammation and obesity. Inflammation impairs the hypothalamic expression of α7 nicotinic acetylcholine receptor (α7nAChR). The α7nAChR is described as the main component of the anti-inflammatory cholinergic pathway in different inflammation models. To assess whether the reduction in α7nAChR expression exacerbates hypothalamic inflammation induced by a high-fat diet (HFD), were used male and female global α7nAChR knockout mouse line in normal or high-fat diet for 4 weeks. Body weight gain, adiposity, glucose homeostasis, hypothalamic inflammation, food intake, and energy expenditure were evaluated. Insulin sensitivity was evaluated in neuronal cell culture. Consumption of an HFD for 4 weeks resulted in body weight gain and adiposity in male Chrna7-/- mice and the hypothalamus of male Chrna7-/- mice showed neuroinflammatory markers, with increased gene expression of pro-inflammatory cytokines and dysregulation in the nuclear factor kappa B pathway. Moreover, male Chrna7-/- mice consuming an HFD showed alterations in glucose homeostasis and serum of Chrna7-/- mice that consumed an HFD impaired insulin signalling in neuronal cell culture experiments. In general, female Chrna7-/- mice that consumed an HFD did not show the phenotypic and molecular changes found in male mice, indicating that there is sexual dimorphism in the analysed parameters. Thus, receptor deletion resulted in increased susceptibility to hypothalamic inflammation and metabolic damage associated with HFD consumption in male mice.

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In many infectious diseases, the pathogen-induced inflammatory response could result in protective immunity that should be regulated to prevent tissue damage and death. In fact, in Trypanosoma cruzi infection, the innate immune and the inflammatory response should be perfectly controlled to avoid significant lesions and death. Here, we investigate the role of Blimp-1 expression in T cells in resistance to T. cruzi infection. Therefore, using mice with Blimp-1 deficiency in T cells (CKO) we determined its role in the controlling parasites growth and lesions during the acute phase of infection. Infection of mice with Blimp-1 ablation in T cells resulted failure the cytotoxic CD8+ T cells and in marked Th1-mediated inflammation, high IFN-γ and TNF production, and activation of inflammatory monocyte. Interestingly, despite high nitric-oxide synthase activation (NOS-2), parasitemia and mortality in CKO mice were increased compared with infected WT mice. Furthermore, infected-CKO mice exhibited hepatic lesions characteristic of steatosis, with significant AST and ALT activity. Mechanistically, Blimp-1 signaling in T cells induces cytotoxic CD8+ T cell activation and restricts parasite replication. In contrast, Blimp-1 represses the Th1 response, leading to a decreased monocyte activation, less NOS-2 activation, and, consequently preventing hepatic damage and dysfunction. These data demonstrate that T. cruzi-induced disease is multifactorial and that the increased IFN-γ, NO production, and dysfunction of CD8+ T cells contribute to host death. These findings have important implications for the design of potential vaccines against Chagas disease.

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The α7nAChR is crucial to the anti-inflammatory reflex, and to the expression of neuropeptides that control food intake, but its expression can be decreased by environmental factors. We aimed to investigate whether microRNA modulation could be an underlying mechanism in the α7nAchR downregulation in mouse hypothalamus following a short-term exposure to an obesogenic diet. Bioinformatic analysis revealed Let-7 microRNAs as candidates to regulate Chrna7, which was confirmed by the luciferase assay. Mice exposed to an obesogenic diet for 3 days had increased Let-7a and decreased α7nAChR levels, accompanied by hypothalamic fatty acids and TNFα content. Hypothalamic neuronal cells exposed to fatty acids presented higher Let-7a and TNFα levels and lower Chrna7 expression, but when the cells were pre-treated with TLR4 inhibitor, Let-7a, TNFα, and Chrna7 were rescued to normal levels. Thus, the fatty acids overload trigger TNFα-induced Let-7 overexpression in hypothalamic neuronal cells, which negatively regulates α7nAChR, an event that can be related to hyperphagia and obesity predisposition in mice.

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Although the diversity of animal groups distributed in Brazil provides countless research opportunities, the current scenario does not follow this demand. The reasons for the disconnections range from inequality in the availability of resources for teaching and research to the focus of researchers on specific groups of animals, while others remain neglected. Training new potential Brazilian researchers interested in Zoology is essential for a greater understanding of this diversity, as well as exposing those potential new researchers to new groups and different work possibilities. Thus, the Summer Course in Zoology (in Portuguese, CVZoo) promoted by the Graduate Program in Zoology at the University of São Paulo, over the last ten years, has been seeking to contribute to this training of new researchers in the field of Zoology, as well as in updating teachers through university extension activities. In order to assess the impacts caused by CVZoo on the academic and professional training of the participants, Google forms were sent to participants in the ten editions of the course, as well as compiled information available on the Lattes Platform. Qualitative and quantitative analyses showed the profile of graduates, their expectations, and perceptions about the course. Based on these data, we demonstrate the CVZoo's efficiency in popularizing Zoology throughout the country in contributing to the decentralization of knowledge as well as in meeting the urgent concerns of making access to knowledge more egalitarian and socially fair.

Embora a diversidade de grupos de animais existentes no Brasil ofereça inúmeras oportunidades de estudo, o cenário atual não acompanha essa demanda. Os motivos para essa desconexão vão desde a desigualdade na disponibilidade de recursos para ensino e pesquisa até o foco de pesquisadores em grupos específicos de animais, enquanto outros permanecem negligenciados. O treinamento de novos pesquisadores interessados em Zoologia é essencial para um maior entendimento da diversidade brasileira, assim como a exposição de tais pesquisadores a novos grupos e diferentes possibilidades de trabalho. O Curso de Verão em Zoologia (CVZoo) promovido pelo Programa de Pós-graduação em Zoologia da Universidade de São Paulo, ao longo de dez anos vem buscando contribuir para a formação de novos(as) pesquisadores(as) na área da Zoologia, bem como na atualização de docentes do Ensino Básico por meio de atividades de extensão universitária. Para avaliar os impactos causados pelo CVZoo na formação acadêmica e profissionalizante dos participantes, foram enviados formulários aos participantes das dez edições do curso, bem como compiladas informações disponíveis na Plataforma Lattes. Análises qualitativas e quantitativas evidenciaram o perfil das pessoas egressas, suas expectativas e percepções acerca do curso oferecido. Com base nesses dados, é apontada a eficiência do CVZoo na popularização da Zoologia por todo o país, contribuindo para a descentralização do conhecimento, bem como atendendo às preocupações prementes de tornar o acesso ao conhecimento mais igualitário e socialmente justo

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Sleep-related phenotypes have been frequently reported in early on-set epileptic encephalopathies and in developmental delay syndromes, in particular in syndromes related to autism spectrum disorder. Yet the convergent pathogenetic mechanisms between these comorbidities are largely unknown. We first performed a gene enrichment study that identified shared risk genes among rare epileptic encephalopathies/neurodevelopmental disorders, rare developmental delay genetic syndromes and sleep disturbances. We then determined cellular and molecular pathways enriched among genes shared between sleep phenotypes and those two early onset mental illnesses, aiming to identify genetic disparities and commonalities among these phenotypic groups. The sleep gene set was observed as significantly overlapped with the two gene lists associated to rare genetic syndromes (i.e., epileptic encephalopathies/neurodevelopmental disorders and developmental delay gene sets), suggesting shared genetic contribution. Similarities across significantly enriched pathways between the two intersect lists comprehended mostly synapse-related pathways, such as retrograde endocannabinoid signaling, serotonergic, and GABAergic synapse. Network analysis indicates epileptic encephalopathies/neurodevelopmental disorders versus sleep-specific clusters and developmental delay versus sleep-specific clusters related to synaptic and transcriptional regulation, respectively. Longstanding functional patterns previously described in epileptic encephalopathies and neurodevelopmental disorders genetic architecture were recaptured after dissecting the overlap between the genes associated to those developmental phenotypes and sleep disturbances, suggesting that during neurodevelopment different molecular and functional mechanisms are related to alterations on circadian rhythm. The overlapping gene set and biological pathways highlighted by this study may serve as a primer for new functional investigations of shared molecular mechanisms between sleep disturbances and rare developmental syndromes.

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We sampled abiotic and food web components in an impacted estuarine system to assess the transfer and fate of rare earth elements (REE). REE (based on dry weight) were measured in sediments, suspended particulate matter (SPM), and organisms from different trophic levels. The highest ∑REE concentrations were measured in sediments (180 ± 4.24 mg kg-1) and SPM (163 ± 12.6 mg kg-1). Phytoplankton (45.7 ± 5.31 mg kg-1), periphyton (51.6 ± 1.81 mg kg-1), and zooplankton (68.5 ± 1.27 mg kg-1) are the major sources of exposure and transfer of REE to the food web. REE concentrations were several orders of magnitude lower in bivalves, crustaceans, and fish (6.01 ± 0.11, 1.22 ± 0.18, and 0.059 ± 0.003 mg kg-1, respectively) than in plankton. The ∑REE declined as a function of the trophic position, as determined by functional feeding groups and δ15N, indicating that REE were subject to trophic dilution. Our study suggests that the consumption of seafood is unlikely to be an important source of REE for humans. However, given the numerous sources of dietary introduction of REE, they should be monitored for a possible harmful cumulative effect. This study provides new key information on REE's baseline concentrations and trophic transfers and patterns.

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The consumption of fruits, vegetables, and cereals in the form of flour has been an alternative for the intake of nutrients, currently seen in a society that seeks a healthier diet. Thus, the assessment of total contents and bioaccessibility is important to better understand the actual intake of nutrients or contaminants present in foods. The objective of this study was to determine the total content and estimate the bioaccessible fraction of Cu, Fe, and Zn in nutritious flours by inductively coupled plasma optical emission spectrometry (ICP OES) after microwave acid digestion. Bioaccessibility was assessed using the in vitro method, taking into account the entire gastrointestinal tract (Unified Bioaccessibility Method (UBM)). The following concentration ranges, in µg g-1, were found: Ca (341-6275), K (2984-13,953), P (476-6110), Na (< 0.39-2995), Fe (1.4-167), Cu (< 0.01-59.6), and Zn (< 0.07-30.3). Principal component analysis (PCA) and hierarchical cluster analysis (HCA) showed a tendency towards the formation of three groups. The bioaccessible fractions for Cu, Fe, and Zn were considered low, ranging from 0.96 to 40% in the gastrointestinal phase and from 4.1 to 100% in the gastric phase.

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Obesity has become a public health problem in recent decades, and during pregnancy, it can lead to an increased risk of gestational complications and permanent changes in the offspring resulting from a process known as metabolic programming. The offspring of obese dams are at increased risk of developing non-alcoholic fatty liver disease (NAFLD), even in the absence of high-fat diet consumption. NAFLD is a chronic fatty liver disease that can progress to extremely severe conditions that require surgical intervention with the removal of the injured tissue. Liver regeneration is necessary to preserve organ function. A range of pathways is activated in the liver regeneration process, including the Hippo, TGFß, and AMPK signaling pathways that are under epigenetic control. We investigated whether microRNA modulation in the liver of the offspring of obese dams would impact gene expression of Hippo, TGFß, and AMPK pathways and tissue regeneration after partial hepatectomy (PHx). Female Swiss mice fed a standard chow or a high-fat diet (HFD) before and during pregnancy and lactation were mated with male control mice. The offspring from control (CT-O) and obese (HF-O) dams weaned to standard chow diet until day 56 were submitted to PHx surgery. Prior to the surgery, HF-O presented alterations in miR-122, miR-370, and Let-7a expression in the liver compared to CT-O, as previously shown, as well as in its target genes involved in liver regeneration. However, after the PHx (4 h or 48 h post-surgery), differences in gene expression between CT-O and HF-O were suppressed, as well as in microRNA expression in the liver. Furthermore, both CT-O and HF-O presented a similar regenerative capacity of the liver within 48 h after PHx. Our results suggest that survival and regenerative mechanisms induced by the partial hepatectomy may overcome the epigenetic changes in the liver of offspring programmed by maternal obesity.

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Bioassay-guided fractionation of dichloromethane extract from Athenaea velutina leaves led to the isolation of three withanolides, all being reported for the first time in this species. They were identified as withacnistin (1), withacnistin acetate (2) and a new withanolide, designated as withalutin (3). The structures were established by spectral data analysis, including MS, 1D and 2D NMR. In addition, in silico ADMET studies were employed to understand the pharmacokinetic properties of these withanolides. The withanolides isolated from A. velutina reduced cancer cell viability with IC50 values ranging from 1.52 to 5.39 µM. In silico prediction revealed that withanolides have good gastrointestinal absorption or oral bioavailability properties; and are not likely to be mutagenic or hepatotoxic. These findings revealed that A. velutina is an important source of cytotoxic withanolides.

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Athenaea velutina is a promising Brazilian shrub with cytotoxic and antimigratory properties against cancer cells. However, the mechanism of induction of cancer cell death and the compounds involved remain unknown. To ascertain these bioactive compounds, bioassay-guided fractionation was performed, alongside the appropriate in vitro tests. A withanolide-rich fraction (FAv_5) from the dichloromethane extract increased cytotoxic activity by 1.5-fold (IC50 = 2.1 µg/mL). Fourteen withanolide steroids were tentatively identified for the first time for this species by mass spectrometry coupled to liquid chromatography (LC MS/MS), including withanolide A, aurelianolide A, and aurelianolide B. FAv_5 significantly decreased cell proliferation, migration, and invasion with a selectivity index greater than 8 for B16F10 cells. Furthermore, flow cytometry with annexin V fluorescein isothiocyanate/propidium iodide (V-FITC/PI) staining showed FAv_5 to promote cell cycle arrest at the G0/G1-phase as well as apoptotic cell death. Overall, these findings highlight A. velutina as a source of withanolide-steroids that inhibit cancer cell proliferation through apoptosis and cell cycle blockade mechanisms. Details on the geographic distribution of A. velutina and species conservation strategies have also been highlighted.

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In Brazil, any advertising strategies that take advantage of the child's judgment or induce consumers to make harmful health choices are considered abusive. However, the efficacy of restrictions on their use on television (TV) food advertising remains poorly understood. This study analysed the extent and nature of abusive techniques according to national regulations and patterns in their use in food-related ads. Cross-sectional studyrecorded the programming of the three most popular TV channels (6 am-12 am), during eight non-consecutive days, in April 2018. Data collection was based on the INFORMAS protocol and two national regulations. Descriptive analyses were used to describe the types of food ads and abusive techniques used in ultra-processed products (UPP) ads. Principal component analysis was applied to identify patterns of abusive marketing techniques and to relate them to specific food groups. More than 90% of food ads included at least one UPP. Overall, 10.1% of UPP ads targeted children and 57.7% used some kind of abusive technique directed to children and adolescents. Most ads contained messages inducing harmful health choices did not present adequate and clear information about the product and contained more than one type of abusive technique. Four out of five patterns in the use of abusive techniques in UPP ads were specifically directed to children, and fast-food meals were associated with three out of five patterns. The high abusiveness of food advertising in UPP ads should be considered a public health concern given their impact on children's food choices and health.

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This work investigated the efficiency of bioremediation of heavy fuel oil (HFO) in aqueous solutions by living Eichhornia crassipes (Mart.) Solms, also known as water hyacinth. Possibility of using post-biosorption macrophytes to produce briquettes was also studied. HFO was characterized by its density, viscosity, and Fourier-transform infrared spectroscopy. Water hyacinth was characterized by scanning electron microscope, pH of zero point of charge, buoyancy, and wettability. Experiments were performed to evaluate effects of contact time and initial oil concentration on biosorption. E. crassipes presented a hydrophobic nature, ideal for the treatment of oily effluents. Hollow structures in macrophytes were also identified, which favor capillary rise and retention of oils of high density and viscosity. Biosorption efficiency of HFO reached 94.8% in tests with initial concentration of 160 mg.L-1. A calorific value of 4022 kcal.kg-1 was obtained in briquettes made of water hyacinth post-biosorption. These results reinforce the great potential of E. crassipes as a sustainable and efficient alternative for treatment of oily effluents.

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Nutritional status during gestation may lead to a phenomenon known as metabolic programming, which can be triggered by epigenetic mechanisms. The Let-7 family of microRNAs were one of the first to be discovered, and are closely related to metabolic processes. Bioinformatic analysis revealed that Prkaa2, the gene that encodes AMPK α2, is a predicted target of Let-7. Here we aimed to investigate whether Let-7 has a role in AMPKα2 levels in the NAFLD development in the offspring programmed by maternal obesity. Let-7 levels were upregulated in the liver of newborn mice from obese dams, while the levels of Prkaa2 were downregulated. Let-7 levels strongly correlated with serum glucose, insulin and NEFA, and in vitro treatment of AML12 with glucose and NEFA lead to higher Let-7 expression. Transfection of Let-7a mimic lead to downregulation of AMPKα2 levels, while the transfection with Let-7a inhibitor impaired both NEFA-mediated reduction of Prkaa2 levels and the fat accumulation driven by NEFA. The transfection of Let-7a inhibitor in ex-vivo liver slices from the offspring of obese dams restored phospho-AMPKα2 levels. In summary, Let-7a appears to regulate hepatic AMPKα2 protein levels and lead to the early hepatic metabolic disturbances in the offspring of obese dams.

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Objectives: Pyridoxine plays a key role in the development of the human nervous system. Several reports suggest that administration of high doses of pyridoxine can be helpful in improving disturbances such as anxiety and pyridoxine-dependent epilepsy, although it has also been associated with a proconvulsive action. In this study, we investigated in developing rats the effects of repeated administration of various doses of pyridoxine on anxiety-like behavior and the brain excitability-related phenomenon known as cortical spreading depression (CSD).Methods: From postnatal day (P) 7 to P27, Wistar rat pups received per gavage pyridoxine hydrochloride (1 mg/kg/day, or 5 mg/kg/day, or 10 mg/kg/day). On P60-70, the animals were tested in the elevated plus maze (EPM) to evaluate anxiety-like behavior. On P71-80, we recorded the CSD (4-hour recording session).Results: Compared with naïve (gavage-free) and saline-treated controls, pyridoxine-treated groups displayed a significant (p < 0.001) increase in CSD propagation velocity and amplitude of the CSD negative direct-current (DC)-shift, and a decrease in the CSD DC-shift duration. These effects were long-lasting and dose-dependent. In the EPM, no significant pyridoxine-associated effect was observed.Discussion: Our data demonstrate a novel action of pyridoxine on an electrical activity-related phenomenon (CSD) in the developing brain, confirming the hypothesis that the chronic treatment with pyridoxine early in life modulates CSD. Data on CSD propagation suggest that pyridoxine at a high dose might act as a prooxidant agent in the developing brain, a hypothesis that deserves further testing.

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OBJECTIVES: To compare the overall diagnostic performance of digital panoramic radiographs obtained with low-dose protocols and to estimate the absorbed dose in the head and neck. MATERIALS AND METHODS: Forty-eight panoramic radiographs were obtained from eight imaging phantoms using six exposure protocols of progressively lower tube voltages (kVp) and currents (mA), as follows: (1) 70 kVp and 12.5 mA, (2) 66 kVp and 10 mA, (3) 66 kVp and 8 mA, (4) 66 kVp and 5 mA, (5) 66 kVp and 4 mA and (6) 66 kVp and 3.2 mA. Five oral radiologists independently evaluated the images and reported all detectable radiographic findings. Intra-examiner reproducibility was assessed by re-evaluation of 25% of the images. The data were analysed using the McNemar and weighted Kappa tests. Absorbed doses of the six protocols were obtained from thermoluminescent dosimeters placed inside a Rando phantom and compared using one-way ANOVA with post hoc Tukey (α = 0.05). RESULTS: The overall diagnostic performance of panoramic radiographs obtained with low-dose protocols did not differ from that of panoramic radiographs obtained with the highest dose (p > 0.05). Moreover, substantial agreement was observed between all protocols. Protocol 1 resulted in the highest absorbed dose and protocols 4, 5 and 6 in the lowest absorbed doses, with the difference being significant (p ≤ 0.05). CONCLUSION: Although digital panoramic radiography is considered a relatively low-dose examination, the radiation dose can be further reduced without negatively affecting its overall diagnostic performance. CLINICAL RELEVANCE: Considering the risks associated with X-rays, digital panoramic radiographs can be obtained at even lower exposure levels.

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An acid digestion procedure of the forage palm (Opuntia ficus-indica Mill and Nopalea cochenilifera) employing a closed digestor block applied full 24 factorial design was optimized. The optimal conditions were HNO3 5.0 mol L-1, 2.0 mL of H2O2 30% m m-1, 120 min of digestion, and heating temperature of 180 °C. The certified reference materials of apple leaves (NIST 1515) and tomato leaves (Agro C1003a) were used to evaluate the accuracy of the analytical method. The concentrations of the macroelements were (in % m m-1) Ca (1.32-3.71), K (0.88-5.29), Mg (0.70-1.78), and P (0.03-0.32). For the microelements, the concentrations (in µg g-1) obtained were As (< 1.39), Cd (< 0.10), Cu (< 0.17-5.6), Fe (8.0-50.2), Na (< 1.85), Sr (41-348), and Zn (17.3-159). Essential elements such as Ca, Mg, and Zn made good contributions to daily intake, being an alternative to meet the nutritional needs of these macroelements and microelements in humans. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were used to evaluate the results, obtaining trends between the samples in relation to their mineral composition.

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OBJECTIVES: This study investigated the use of persuasive advertising strategies in ultra-processed food (UPF) advertisements broadcast on the three most popular free-to-air television channels in Brazil. METHODS: The programming of the selected channels was recorded on eight non-consecutive days from April 2018 (6:00 am-12:00 am). Information from each advertising piece was collected through an electronic questionnaire based on the INFORMAS protocol. Food products were classified according to the NOVA classification system. Marketing strategies were investigated in UPF advertisements and stratified into three groups. Principal component analysis was used to identify patterns of strategies. Linear regression models were employed to investigate the association between the patterns and food groups. RESULTS: In total, 90.77% of the food-related advertisements contained at least one UPF, and 96% of them included one or more persuasive advertising strategies. Five advertising patterns were identified and associated with the UPF food groups. CONCLUSIONS: The results showed that food advertising on Brazilian free television is marked by UPF, with the predominant use of persuasive advertising strategies, demonstrating a lack of enforcement of the current regulatory legislation in the country.

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This study investigated the effect of non-periodized training performed at 80, 100 and 120% of the anaerobic threshold intensity (AnT) and a linear periodized training model adapted for swimming rats on the gene expression of monocarboxylate transporters 1 and 4 (MCT1 and 4, in soleus and gastrocnemius muscles), protein contents, blood biomarkers, tissue glycogen, body mass, and aerobic and anaerobic capacities. Sixty Wistar rats were randomly divided into 6 groups (n = 10 per group): a baseline (BL; euthanized before training period), a control group (GC; not exercised during the training period), three groups exercised at intensities equivalent to 80, 100 and 120% of the AnT (G80, G100 and G120, respectively) at the equal workload and a linear periodized training group (GPE). Each training program lasted 12 weeks subdivided into three periods: basic mesocycle (6 weeks), specific mesocycle (5 weeks) and taper (1 week). Although G80, G100 and G120 groups were submitted to monotony workload (i.e. non-modulation at intensity or volume throughout the training program), rodents were evaluated during the same experimental timepoints as GPE to be able comparisons. Our main results showed that all training programs were capable to minimize the aerobic capacity decrease promoted by age, which were compared to control group. Rats trained in periodization model had reduced levels of lipid blood biomarkers and increased hepatic glycogen stores compared to all other trained groups. At the molecular level, only expressions of MCT1 in the muscle were modified by different training regimens, with MCT1 mRNA increasing in rats trained at lower intensities (G80), and MCT1 protein content showed higher values in non-periodized groups compared to pre-training and GPE. Here, training at different intensities but at same total workload promoted similar adaptations in rats. Nevertheless, our results suggested that periodized training seems to be optimize the physiological responses of rats.

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BACKGROUND: The aim of this study was to integrate the available data published on radiation-induced sarcoma of the oral cavity into an analysis of its clinical features, treatment modalities and prognostic factors. METHODS: An electronic search was undertaken in September 2019. The eligibility criteria included publications that had enough clinical and histological information to confirm the diagnosis. RESULTS: Forty-two publications with 122 radiation-induced sarcoma of the oral cavities (RISOCs) were included. The mean latency period was 114 months and mean radiation total dose was 62.5 Gy. The tumors were more prevalent in males between 50 and 60 years old and the mandible was the most affected site. Osteosarcoma was the most prevalent histological type and patients were mostly treated with radical surgery. CONCLUSIONS: RISOC showed a poor survival rate of 15.1% in 5-year follow-up. Gender and histological type were independently associated with survival.

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