GDP-mannose pyrophosphorylase is an efficient target in Xanthomonas citri for citrus canker control.

Xanthomonas citri subsp. citri (Xcc) is a bacterium that causes citrus canker, an economically important disease that results in premature fruit drop and reduced yield of fresh fruit. In this study, we demonstrated the involvement of XanB, an enzyme with phosphomannose isomerase (PMI) and guanosine diphosphate-mannose pyrophosphorylase (GMP) activities, in Xcc pathogenicity. Additionally, we found that XanB inhibitors protect the host against Xcc infection. Besides being deficient in motility, biofilm production, and ultraviolet resistance, the xanB deletion mutant was unable to cause disease, whereas xanB complementation restored wild-type phenotypes. XanB homology modeling allowed in silico virtual screening of inhibitors from databases, three of them being suitable in terms of absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) properties, which inhibited GMP (but not PMI) activity of the Xcc recombinant XanB protein in more than 50%. Inhibitors reduced citrus canker severity up to 95%, similarly to copper-based treatment. xanB is essential for Xcc pathogenicity, and XanB inhibitors can be used for the citrus canker control. IMPORTANCE: Xcc causes citrus canker, a threat to citrus production, which has been managed with copper, being required a more sustainable alternative for the disease control. XanB was previously found on the surface of Xcc, interacting with the host and displaying PMI and GMP activities. We demonstrated by xanB deletion and complementation that GMP activity plays a critical role in Xcc pathogenicity, particularly in biofilm formation. XanB homology modeling was performed, and in silico virtual screening led to carbohydrate-derived compounds able to inhibit XanB activity and reduce disease symptoms by 95%. XanB emerges as a promising target for drug design for control of citrus canker and other economically important diseases caused by Xanthomonas sp.

Description of new species of Mycobacterium terrae complex isolated from sewage at the São Paulo zoological park foundation in Brazil.

Five mycobacterial isolates from sewage were classified as members of the genus Mycobacterium but presented inconclusive species assignments. Thus, the isolates (MYC017, MYC098, MYC101, MYC123 and MYC340) were analyzed by phenotypical, biochemical, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and genomic features to clarify their taxonomic position. Phenotypic analysis and biochemical tests did not distinguish these isolates from other non-pigmented mycobacteria. In contrast, MALDI-TOF MS analysis showed that isolates were not related to any previously described Mycobacterium species. Comparative genomic analysis showed values of ANI and dDDH between 81.59-85.56% and 24.4-28.8%, respectively, when compared to the genomes of species of this genus. In addition, two (MYC101 and MYC123) presented indistinguishable protein spectra from each other and values of ANI = 98.57% and dDDH = 97.3%, therefore being considered as belonging to the same species. Phylogenetic analysis grouped the five isolates within the Mycobacterium terrae complex (MTC) but in a specific subclade and separated from the species already described and supported by 100% bootstrap value, confirming that they are part of this complex but different from earlier described species. According to these data, we propose the description of four new species belonging to the Mycobacterium genus: (i) Mycobacterium defluvii sp. nov. strain MYC017T (= ATCC TSD-296T = JCM 35364T), (ii) Mycobacterium crassicus sp. nov. strain MYC098T (= ATCC TSD-297T = JCM 35365T), (iii) Mycobacterium zoologicum sp. nov. strain MYC101T (= ATCC TSD-298T = JCM 35366T) and MYC123 (= ATCC BAA-3216 = JCM 35367); and (iv) Mycobacterium nativiensis sp. nov. strain MYC340T (= ATCC TSD-299T = JCM 35368T).

Ligand-based virtual screening, molecular dynamics, and biological evaluation of repurposed drugs as inhibitors of Trypanosoma cruzi proteasome.

Chagas disease is a well-known Neglected Tropical Disease, mostly endemic in continental Latin America, but that has spread to North America and Europe. Unfortunately, current treatments against such disease are ineffective and produce known and undesirable side effects. To find novel effective drug candidates to treat Chagas disease, we uniquely explore the Trypanosoma cruzi proteasome as a recent biological target and, also, apply drug repurposing through different computational methodologies. For this, we initially applied protein homology modeling to build a robust model of proteasome ß4/ß5 subunits, since there is no crystallographic structure of this target. Then, we used it on a drug repurposing via a virtual screening campaign starting with more than 8,000 drugs and including the methodologies: ligand-based similarity, toxicity predictions, and molecular docking. Three drugs were selected concerning their favorable interactions at the protein binding site and subsequently submitted to molecular dynamics simulations, which allowed us to elucidate their behavior and compare such theoretical results with experimental ones, obtained in biological assays also described in this paper.Communicated by Ramaswamy H. Sarma.

Skeletal expansion using a miniscrew-assisted rapid palatal expansion in a 50-year-old patient.

This case report illustrates a nonsurgical treatment plan using a miniscrew-assisted rapid palatal expander (MARPE) in a 50-year-old patient with maxillary transverse deficiency. The MARPE appliance consisted of a conventional Hyrax expander anchored to 4 orthodontic miniscrews. The exact locations of the miniscrews were determined with virtual planning software. Cone-beam computed tomography (CBCT) scans were superimposed on the maxillary digital model, and 3-dimensional-printed surgical guides were used to accurately position the mini-implants. A slow expansion protocol was used, and the appliance was held in place during the entire treatment (almost 20 months). Pretreatment, postexpansion, and posttreatment CBCT scans show the parallel expansion obtained without dental torque compensation or bite opening. The posttreatment scan showed that a long period is required to complete the midpalatal suture mineralization. MARPE has proven effective in correcting transverse discrepancies, even in adults. However, posttreatment CBCT imaging showed incomplete ossification of the midpalatal suture, demonstrating that the retention period should be extended in some adult patients.

Preferential solvation and optical properties of eumelanin building blocks in binary mixture of methanol and water.

Employing a sequential quantum mechanical/molecular mechanical approach for polar protic solvents, we study the absorption spectrum of eumelanin building blocks including monomers, dimers, and tetramers in pure water and methanol and three water-methanol binary mixtures having water molar fractions (Xw = 0.25, 0.50, and 0.75). The binary mixture of solvents is a common situation in experiments, but theoretical studies are limited to the use of continuum models. Here, we use explicit solvent molecules, and specific solute-solvent interaction is analyzed and seen to play an important role. Effects of the electronic polarization of solute by the environment were included using a reliable iterative scheme. The results illustrate that the monomers, dimers, and tetramers are preferably solvated by methanol, but the composition of the mixture in the vicinity of the solute molecules is different from the bulk composition with a preferential microsolvation (hydrogen bonds) in water for most species considered. It is observed that the short-range electrostatic polarization effects of the hydrogen bonds lead to a slight blue shift of the excitation energies when the concentration of water in the mixture is enhanced. For the same species, there is an enhancement of the higher-energy absorption intensity caused by long-range electrostatic interactions with the environment and that the behavior of the experimental spectrum, which is characterized by a nearly monotonic decay from the ultraviolet to the infrared, is qualitatively reproduced by the superposition of the absorption spectra of monomers, dimers, and tetramers in the liquid phase.

Potential colchicine binding site inhibitors unraveled by virtual screening, molecular dynamics and MM/PBSA.

Microtubules have been widely studied in recent decades as an important pharmacological target for the treatment of cancer especially due to its key role in the mitosis process. Among the constituents of the microtubules, αß-tubulin dimers stand out in view of their four distinct interaction sites, including the so-called colchicine binding site (CBS) - a promising target for the development of new tubulin modulators. When compared to other tubulin sites, targeting the CBS is advantageous because this site is able to host ligands with lower molecular volume and lipophilicity, thus reducing the chances of entailing the phenomenon of multiple drug resistance (MDR) - one of the main reasons of failure in chemotherapy. However, colchicine, the first ligand ever discovered with affinity towards the CBS, despite modulating the action of microtubules, has shown toxicity in clinical studies. Therefore, in order to expand the known chemical space of scaffolds capable of interacting with CBS and to design non-toxic colchicine binding site inhibitors, we conducted a robust virtual screening pipeline. This has been rigorously validated and consisted of ligand- and structure-based methodologies, which allowed us to select four promising CBS inhibitors called tubLCQF1-4. These four compounds were also evaluated with long trajectories molecular dynamics simulations and respective results were used for the theoretical determination of the free energy released in the formation of the complexes, using the Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) methodology.

Cadmium affects cell niches maintenance in Arabidopsis thaliana post-embryonic shoot and root apical meristem by altering the expression of WUS/WOX homolog genes and cytokinin accumulation.

Cadmium (Cd) is one of the most widespread polluting heavy metals in both terrestrial and aquatic environments and represents an extremely significant pollutant causing severe environmental and social problems due to its high toxicity and large solubility in water. In plants, the root is the first organ that get in contact with Cd. It is absorbed by the root system and translocated to the shoot and leaves through xylem loading, causing a variety of genetic, biochemical, and physiological damages. Cd inhibits both the root and shoot growth, but the mechanisms underlying this inhibition remain elusive. In this context in the present work we focused the attention on the effects of Cd on meristem size and organization of both shoot and root. To this aim morpho-histological and molecular analyses were carried out on 5 days old seedlings exposed or not to Cd (100 µM and 150 µM for 24) of wild type and transgenic lines expressing molecular markers with an important role in shoot and root pattern organization. More precisely, we monitored the expression pattern of WUS/CLV3 and WOX5 transcription factors involved in the establishment and maintenance of stem cell niche and the control of meristem size and of TCSn::GFP cytokinin-sensitive sensor as relevant components of hormone circuit controlling shoot and root growth. The results highlighted that the treatments with Cd impacts shoot and root size and shape by altering the paralogous WOX genes expression via cytokinin accumulation.

Identification of known drugs as potential SARS-CoV-2 Mpro inhibitors using ligand- and structure-based virtual screening.

Background: The new coronavirus pandemic has had a significant impact worldwide, and therapeutic treatment for this viral infection is being strongly pursued. Efforts have been undertaken by medicinal chemists to discover molecules or known drugs that may be effective in COVID-19 treatment - in particular, targeting the main protease (Mpro) of the virus. Materials & methods: We have employed an innovative strategy - application of ligand- and structure-based virtual screening - using a special compilation of an approved and diverse set of SARS-CoV-2 crystallographic complexes that was recently published. Results and conclusion: We identified seven drugs with different original indications that might act as potential Mpro inhibitors and may be preferable to other drugs that have been repurposed. These drugs will be experimentally tested to confirm their potential Mpro inhibition and thus their effectiveness against COVID-19.

Molecular dynamic simulations, GIAO-NMR and TD-DFT spectroscopy analyze for zwitterionic isoleucine (ILE)N , 1 ≤ N ≤ 6, in water solution.

In this article, we investigate the effects of the isoleucine (ILE)N amino acid chain growth, N = 1.0.6, the ILE conformational effect as well as the solvent presence on the electrical and magnetic spectroscopic properties when these compounds are in aqueous solution. Computational molecular dynamics simulations were performed to include the solvent medium and generate uncorrelated configurations involving solute-solvent structures. The charge point model for solvent was used to obtain the results for quantum mechanical calculation, in special DFT calculations, for (ILE)N structures. Our results for the magnetic shielding constant obtained via GIAO-DFT-NMR calculations show that there is evidence of a magnetic behavior that characterizes the number of peptide bonds and, therefore, how the N isoleucine polypeptide chain is composed. TD-DFT results also show an absorption band shift to larger wavelengths indicating a dependence on N growth.

15N NMR Shifts of Eumelanin Building Blocks in Water: A Combined Quantum Mechanics/Statistical Mechanics Approach.

Theoretical results for the magnetic shielding of protonated and unprotonated nitrogens of eumelanin building blocks including monomers, dimers, and tetramers in gas phase and water are presented. The magnetic property in water was determined by carrying out Monte Carlo statistical mechanics sampling combined with quantum mechanics calculations based on the gauge-including atomic orbitals approach. The results show that the environment polarization can have a marked effect on nitrogen magnetic shieldings, especially for the unprotonated nitrogens. Large contrasts of the oligomerization effect on magnetic shielding show a clear distinction between eumelanin building blocks in solution, which could be detected in nuclear magnetic resonance experiments. Calculations for a π-stacked structure defined by the dimer of a tetrameric building block indicate that unprotonated N atoms are significantly deshielded upon π stacking, whereas protonated N atoms are slightly shielded. The results stress the interest of NMR experiments for a better understanding of the eumelanin complex structure.

Virtual screening, ADME/Tox predictions and the drug repurposing concept for future use of old drugs against the COVID-19.

The new Coronavirus (SARS-CoV-2) is the cause of a serious infection in the respiratory tract called COVID-19. Structures of the main protease of SARS-CoV-2 (Mpro), responsible for the replication of the virus, have been solved and quickly made available, thus allowing the design of compounds that could interact with this protease and thus to prevent the progression of the disease by avoiding the viral peptide to be cleaved, so that smaller viral proteins can be released into the host's plasma. These structural data are extremely important for in silico design and development of compounds as well, being possible to quick and effectively identify potential inhibitors addressed to such enzyme's structure. Therefore, in order to identify potential inhibitors for Mpro, we used virtual screening approaches based with the structure of the enzyme and two compounds libraries, targeted to SARS-CoV-2, containing compounds with predicted activity against Mpro. In this way, we selected, through docking studies, the 100 top-ranked compounds, which followed to subsequent studies of pharmacokinetic and toxicity predictions. After all the simulations and predictions here performed, we obtained 10 top-ranked compounds that were again in silico analyzed inside the Mpro catalytic site, together some drugs that are being currently investigated for treatment of COVID-19. After proposing and analyzing the interaction modes of these compounds, we submitted one molecule then selected as template to a 2D similarity study in a database containing drugs approved by FDA and we have found and indicated Apixaban as a potential drug for future treatment of COVID-19.

Identification of novel αß-tubulin modulators with antiproliferative activity directed to cancer therapy using ligand and structure-based virtual screening.

Among several strategies related to cancer therapy targeting the modulation of αß-tubulin has shown encouraging findings, more specifically when this is achieved by inhibitors located at the colchicine binding site. In this work, we aim to fish new αß-tubulin modulators through a diverse and rational VS study, and thus, exhibiting the development of two VS pipelines. This allowed us to identify two compounds 5 and 9 that showed IC50 values of 19.69 and 21.97 µM, respectively, towards possible modulation of αß-tubulin, such as assessed by in vitro assays in C6 glioma and HEPG2 cell lines. We also evaluated possible mechanisms of action of obtained hits towards the colchicine binding site of αß-tubulin by using docking approaches. In addition, assessment of the stability of the active (5 and 9) and inactive compounds (3 and 13) within the colchicine binding site was carried out by molecular dynamics (MD) simulations, highlighting the solvent effect and revealing the compound 5 as the most stable in the complex. At last, deep analysis of these results provided some valuable insights on the importance of using mixed ligand- and structure-based strategies in VS campaigns, in order to achieve higher chemical diversity and biological effect as well.

Identification of potential target genes associated with the reversion of androgen-dependent skeletal muscle atrophy.

Muscle wasting or atrophy is extensively associated with human systemic diseases including diabetes, cancer, and kidney failure. Accumulating evidence from transcriptional profiles has noted that a common set of genes, termed atrogenes, is modulated in atrophying muscles. However, the transcriptional changes that trigger the reversion or attenuation of muscle atrophy have not been characterized at the molecular level until now. Here, we applied cDNA microarrays to investigate the transcriptional response of androgen-sensitive Levator ani muscle (LA) during atrophy reversion. Most of the differentially expressed genes behaved as atrogenes and responded to castration-induced atrophy. However, seven genes (APLN, DUSP5, IGF1, PIK3IP1, KLHL38, PI15, and MKL1) did not respond to castration but instead responded exclusively to testosterone replacement. Considering that almost all proteins encoded by these genes are associated with the reversion of atrophy and may function as regulators of cell proliferation/growth, our results provide new perspectives on the existence of anti-atrogenes.

Avaliação da qualidade microbiológica dos peixes comercializados no mercado público das Rocas em Natal, RN

No Brasil os peixes são um dos alimentos mais consumidos no grupo dos pescados, pelo fato da maioria das pessoas não poderem consumir outro alimento do mesmo grupo, devido ao alto custo. O objetivo deste trabalho foi avaliar a qualidade microbiológica dos peixes comercializados no Mercado Público das Rocas na cidade de Natal-RN, discutindo-se os parâmetros higienicossanitários dos locais onde são comercializados. Trata-se de uma pesquisa quantitativa e experimental. A coleta de dados contou com análise microbiológica dos peixes comercializados em diferentes boxes onde são vendidos, aplicando-se testes presuntivo e confirmativo para Coliformes totais, Estafilococos coagulase positiva e Salmonella sp. Quanto ao resultado encontrado, observou-se, em um total de 20 amostras coletadas em dias alternados, a presença de 90% na contagem de Coliformes a 35 °C de até 10³ NMP/g, já no teste de Coliformes a 45 °C foi encontrada a quantidade de 10%, com contagem inferior a 10¹ NMP/g, e 70% apresentou contagem significativa para Estafilococos coagulase positiva, apresentado valor superior a 105 NMP/g. Vale ressaltar que há necessidade em adotar medidas de controle por parte dos manipuladores, no que diz respeito à qualidade e higienização dos boxes

In Brazil, fish are one of the most consumed foods in the fish group, because most people can not consume other food from the same group, due to the high cost. The objective of this work was to evaluate the microbiological quality of the fish commercialized in the Public Market of the Rocks in the city of Natal-RN, in which the hygienic sanitary parameters of the fish selling points were discussed. This is a quantitative and qualitative research. Data collection included microbiological analysis of the fish commercialized in different boxes selling the same, in which preparation and dilution were carried out, a presumptive and confirmatory test for Total Coliforms, Positive Coagulase Staphylococci and Salmonella sp. As for the result found, it was observed that in a general total of 20 samples that had collections on alternate days, where in one week 10 samples were collected, and soon after seven days the remaining 10 samples were collected, it was verified the presence of 90% in the Coliform counts at 35°C of up to 10³ NMP/g was observed, already in the Coliform test at 45°C was found the amount of 10%, with a count lower than 10¹ NMP/g, and in 70% presented a significant count for Staphylococcus Coagulase Positive, presenting a value higher than 105 NMP/g. It is worth mentioning that there is a need to adopt control measures on the part of the manipulators, regarding the quality of hygiene of the boxes

Avaliação da qualidade microbiológica dos peixes comercializados no Mercado Público das Rocas em Natal, RN

No Brasil os peixes são um dos alimentos mais consumidos no grupo dos pescados, pelo fato da maioria das pessoas não poderem consumir outro alimento do mesmo grupo, devido ao alto custo. O objetivo deste trabalho foi avaliar a qualidade microbiológica dos peixes comercializados no Mercado Público das Rocas na cidade de Natal-RN, discutindo-se os parâmetros higienicossanitários dos locais onde são comercializados. Trata-se de uma pesquisa quantitativa e experimental. A coleta de dados contou com análise microbiológica dos peixes comercializados em diferentes boxes onde são vendidos, aplicando-se testes presuntivo e confirmativo para Coliformes totais, Estafilococos coagulase positiva e Salmonella sp. Quanto ao resultado encontrado, observou-se, em um total de 20 amostras coletadas em dias alternados, a presença de 90% na contagem de Coliformes a 35°C de até 10

ln Brazil, fish are one of the most consumed foods in the fish group, because most people can not consume other food from the same group, due to the high cost. The objective of this work was to evaluate the microbiological quality of the fish commercialized in the Public Market of the Rocks in the city of Natal-RN, in which the hygienic sanitary parameters of the fish selling points were discussed. This is a quantitative and qualitative research. Data collection included microbiological analysis of the fish commercialized in different boxes selling the same, in which preparation and dilution were carried out, a presumptive and confirmatory test for Total Coliforms, Positive Coagulase Staphylococci and Salmonella sp. As for the result found, it was observed that in a general total of 20 samples that had collections on alternate days, where in one week 10 samples were collected, and soon after seven days the remaining 10 samples were collected, it was verified the presence of 90% in the Coliform counts at 35°C of up to 10

Insertion torque values and success rates for paramedian insertion of orthodontic mini-implants : A retrospective study.

OBJECTIVES: Orthodontic mini-implants (OMIs) are a reliable method to provide temporary orthodontic anchorage. We hypothesized that there is an optimal insertion torque (<10 Ncm) that can be used to ensure the success of self-drilling OMIs in the paramedian region. PATIENTS AND METHODS: Included were 40 (26 females, 14 males) consecutive patients requiring palatal skeletal anchorage. Mean age was 17.3 years (range 11.0-44.6 years) for female patients and 15.7 years (range 10.6-36.9 years) for male patients. A total of 22 patients received a Beneslider according to Wilmes for the distalization of maxillary first molars, 10 patients received a Mesialslider for the mesialization of maxillary first molars, and 8 patients received a bone-borne rapid palatal expansion (RPE) appliance. Torque values of 10-15 Ncm were recorded in 46.3% of the OMIs and 15-20 Ncm in 35% of OMIs. OMIs that endured the orthodontic force applied for ≥6 months were considered as success. RESULTS: The overall success rate was 98.8%. No significant differences were found between insertion torque values with respect to the right and left sides, Jarabak's ratio, facial axis, and Frankfort to mandibular plane angle. There were no significant differences in the OMIs insertion torques with regard to the different appliances. No association was found between insertion torque and vertical skeletal morphology. CONCLUSION: With an overall success rate of 98.8%, the study hypothesis that greater insertion torque (>10 Ncm) will decrease the success rate and increase palatal OMI failure was rejected.

Análise microbiológica de fast foods comercializados por ambulantes no centro da cidade de Natal, RN / Microbiological analysis of fast foods marketed by street vendors in the city center of Natal, RN

[{"text": "O hábito de realizar refeições fora\r\ndo domicílio, expõe os consumidores\r\nao risco de contraírem doenças\r\nveiculadas por alimentos; tendo em\r\nvista tal situação, o presente estudo\r\nteve como objetivo desenvolver uma\r\nanálise microbiológica dos fast foods\r\nmais consumidos. Foram selecionados\r\ncinco amostras de cada alimento\r\ntotalizando 25, dentre estes estão coxinha,\r\ncachorro-quente, batata-frita,\r\npastel de forno e espetinho de carne,\r\ntodos estes alimentos colhidos em\r\nembalagens esterilizadas e encaminhadas\r\npara o laboratório de microbiologia\r\nda Universidade Potiguar,\r\nonde foram realizadas análises microbiológicas\r\npara Staphylococcus\r\ncoagulase positiva, coliformes totais\r\ne termotolerantes, e Salmonella sp.\r\nA metodologia empregada seguiu os\r\npadrões microbiológicos recomendados\r\npela resolução RDC nº 12 da\r\nAgência Nacional de Vigilância Sanitária\r\nde acordo com as normas da\r\nAmerican Public Health Association.\r\nOs resultados obtidos mostraram que\r\n80% das coxinhas, 40% dos pastéis\r\nde forno, 60% das batatas-fritas e\r\n60% de cachorros-quentes, com exceção\r\ndo espetinho de carne, apresentaram\r\ncoliformes totais; quanto à\r\ncontagem de Staphylococcus aureus\r\ntodos superaram o limite máximo\r\ndeterminado pela legislação e todas\r\nas amostras apresentaram resultados\r\nnegativos para a pesquisa de Salmonella\r\nsp. Dessa forma, conclui-se que\r\nhá necessidade de aperfeiçoamento\r\nnos cuidados e nas condições de produção,\r\narmazenamento e comercialização\r\ndos alimentos analisados, bem\r\ncomo, há necessidade de inspeção\r\neficaz por parte dos órgãos de fiscalização.(AU)", "_i": "pt"}]

Qualidade microbiológica do queijo de manteiga comercializado em supermercados e feiras livres da cidade de Natal-RN / Microbiological quality of butter cheese marketed in supermarkets and free trade fairs in the city of Natal-RN

O queijo de manteiga é um produto típico da região Nordeste, sendo produzido industrialmente e em grande parte de forma artesanal. O objetivo do estudo foi avaliar a qualidade microbiológica do queijo de manteiga comercializado em supermercados e feiras livres da cidade de Natal, RN. Foram analisadas 15 amostras de queijos provenientes de supermercados e 15 amostras de queijos comercializados em feiras livres. Foi realizada a pesquisa de coliformes totais e coliformes a 45ºC, Salmonella spp e contagem de Estafilococos coagulase positiva. A metodologia utilizada foi a descrita pela APHA (2001). Os resultados revelaram que 30% das amostras excederam os limites estabelecidos pela legislação para coliformes a 45oC e 90% para Estafilococos coagulase positiva, portanto, maior atenção devem ter as autoridades sanitárias, uma vez que tais produtos podem colocar em risco a saúde do consumidor.