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Glass ceramics are widely used to manufacture esthetic veneers, inlays, onlays, and crowns. Although the clinical survival rates ofglass-ceramic restorations arefavorable,fractures or chips are common. Certain cases can be repaired with direct composite. AIM: The aim of this study was to investigate the interaction effect of different designs and surface treatments on the load-to-failure of lithium disilicate glass-ceramic repaired with nanofilled composite. MATERIALS AND METHOD: Lithium-disilicate glass-ceramic slabs (IPS e.max Press, Ivoclar Vivadent) with three different designs of the top surface (flat, single plateau, or doubleplateau) (n=U) received 'no treatment', '5% HF etching', or "AI2O3 sandblasting". HF-etched and sandblasted slabs also received silane and universal one-step adhesive application. All slabs were incrementally repaired with nanofilled composite (Filtek Z350, 3M ESPE) up to6 mm above the highest ceramic top plateau. Specimens were stored in artificial saliva at 37 °C for 21 days and then subjected to 1,000 thermocycles between 5 and 55 °C. The interface composite-ceramic of each specimen was tensile tested until failure in a universal testing machine and the mode of failure was determined under a stereomicroscope. The ceramic surface morphology of one representative tested specimen from each subgroup (design/surface treatment) was observed through scanning electron microscopy (SEM). RESULTS: Regardless of ceramic design, the absence of surface treatment resulted in significantly lower load-to-failure values. No significant differences in load-to-failure values were observed between HF-etched and sandblasted specimens for the flat design; however, HF etching resulted in significantly higher load-to-failure values than sandblasting for both single plateau and double plateau designs. The majority (60%) of HF-etched specimens with single plateau or double plateau presented mixed failures. SEM photomicrographs showed that HF-etched specimens had smoother surfaces than sandblasted specimens. CONCLUSION: The surface treatment of a defective lithium disilicate glass-ceramic restoration has more influence than its macroscopic design on the retention of the composite repair. HF etching seems to provide higher bond strength to the composite repair.

Embora fraturas e lascamento de restauragoes vitrocerámicas sejam comuns, alguns casos podem ser reparados com compósito direto. OBJETIVO: investigar o efeito da interagao de diferentes formas e tratamentos de superficie na carga de ruptura de uma vitrocerámica reforgada com dissilicato de litio reparada com compósito nanoparticulado. MATERIAIS E MÉTODOS: A superficie superior de espécimes de vitroceramica (IPS e.max Press, Ivoclar Vivadent) foi preparada com tres formas (plana, plato único, ou duplo) e recebeu (n=11): 'nenhum tratamento', 'condicionamento com ácido hidrofluoridrico 5%', ou 'jateamento com AfOf. Ambos espécimes condicionados e jateados receberam silano e adesivo universal. Todos os espécimes foram reparados incrementalmente com compósito (Filtek Z350, 3M ESPE) até6 mm acima do plato cerámico mais alto, armazenados em saliva artificial á 37 °C por 21 dias, e submetidos á 1.000 termociclos (5 e 55 °C). A interface compósito-cerámica de cada amostra foi testada á tragao até sua falha em máquina universal e o modo de falha foi determinado com estereomicroscópio. A morfologia da superficie de uma amostra representativa de forma/tratamento de superficie foi observada através de microscopia eletronica de varredura (MEV). RESULTADOS: Independentemente da forma ceramica, a ausencia de tratamento superficial resultou em valores de carga de ruptura significativamente menores. Nao foi observada differenga significativa entre os espécimes planos condicionados ou jateados; no entanto, o condicionamento resultou em valores significativamente maiores que o jateamento para espécimes com plato único e duplo. A maioria (60%) dos espécimes condicionados e com plato único ou duplo apresentou falhas mistas. Imagens SEM demonstraram rugosidade superficial mais regular dos espécimes condicionados que os jateados. CONCLUSÕES: O tratamento superficial de uma restauragao defeituosa de vitrocerámica reforgada por dissilicato de litio tem maior influencia na retengao do reparo de compósito do que sua forma macroscópica; ainda, o condicionamento com ácido hidrofluoridrico parece proporcionar maior resistencia de uniao ao reparo com compósito.

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ABSTRACT Glass ceramics are widely used to manufacture esthetic veneers, inlays, onlays, and crowns. Although the clinical survival rates ofglass-ceramic restorations arefavorable,fractures or chips are common. Certain cases can be repaired with direct composite. Aim The aim of this study was to investigate the interaction effect of different designs and surface treatments on the load-to-failure of lithium disilicate glass-ceramic repaired with nanofilled composite. Materials and Method Lithium-disilicate glass-ceramic slabs (IPS e.max Press, Ivoclar Vivadent) with three different designs of the top surface (flat, single plateau, or doubleplateau) (n=U) received 'no treatment', '5% HF etching', or "AI2O3 sandblasting". HF-etched and sandblasted slabs also received silane and universal one-step adhesive application. All slabs were incrementally repaired with nanofilled composite (Filtek Z350, 3M ESPE) up to6 mm above the highest ceramic top plateau. Specimens were stored in artificial saliva at 37 °C for 21 days and then subjected to 1,000 thermocycles between 5 and 55 °C. The interface composite-ceramic of each specimen was tensile tested until failure in a universal testing machine and the mode of failure was determined under a stereomicroscope. The ceramic surface morphology of one representative tested specimen from each subgroup (design/surface treatment) was observed through scanning electron microscopy (SEM). Results Regardless of ceramic design, the absence of surface treatment resulted in significantly lower load-to-failure values. No significant differences in load-to-failure values were observed between HF-etched and sandblasted specimens for the flat design; however, HF etching resulted in significantly higher load-to-failure values than sandblasting for both single plateau and double plateau designs. The majority (60%) of HF-etched specimens with single plateau or double plateau presented mixed failures. SEM photomicrographs showed that HF-etched specimens had smoother surfaces than sandblasted specimens. Conclusion The surface treatment of a defective lithium disilicate glass-ceramic restoration has more influence than its macroscopic design on the retention of the composite repair. HF etching seems to provide higher bond strength to the composite repair.

RESUMO Embora fraturas e lascamento de restauragoes vitrocerámicas sejam comuns, alguns casos podem ser reparados com compósito direto. Objetivo investigar o efeito da interagao de diferentes formas e tratamentos de superficie na carga de ruptura de uma vitrocerámica reforgada com dissilicato de litio reparada com compósito nanoparticulado. Materials e Método A superficie superior de espécimes de vitroceramica (IPS e.max Press, Ivoclar Vivadent) foi preparada com tres formas (plana, plato único, ou duplo) e recebeu (n=11): 'nenhum tratamento', 'condicionamento com ácido hidrofluoridrico 5%', ou 'jateamento com AfOf. Ambos espécimes condicionados e jateados receberam silano e adesivo universal. Todos os espécimes foram reparados incrementalmente com compósito (Filtek Z350, 3M ESPE) até6 mm acima do plato cerámico mais alto, armazenados em saliva artificial á 37 °C por 21 dias, e submetidos á 1.000 termociclos (5 e 55 °C). A interface compósito-cerámica de cada amostra foi testada á tragao até sua falha em máquina universal e o modo de falha foi determinado com estereomicroscópio. A morfologia da superficie de uma amostra representativa de forma/tratamento de superficie foi observada através de microscopia eletronica de varredura (MEV). Resultados Independentemente da forma ceramica, a ausencia de tratamento superficial resultou em valores de carga de ruptura significativamente menores. Nao foi observada differenga significativa entre os espécimes planos condicionados ou jateados; no entanto, o condicionamento resultou em valores significativamente maiores que o jateamento para espécimes com plato único e duplo. A maioria (60%) dos espécimes condicionados e com plato único ou duplo apresentou falhas mistas. Imagens SEM demonstraram rugosidade superficial mais regular dos espécimes condicionados que os jateados. Conclusoes O tratamento superficial de uma restauragao defeituosa de vitrocerámica reforgada por dissilicato de litio tem maior influencia na retengao do reparo de compósito do que sua forma macroscópica; ainda, o condicionamento com ácido hidrofluoridrico parece proporcionar maior resistencia de uniao ao reparo com compósito.

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A series of hybrid inhibitors, combining pharmacophores of known kinase inhibitors bearing anilino-purines (ruxolitinib, ibrutinib) and benzohydroxamate HDAC inhibitors (nexturastat A), were generated in the present study. The compounds have been synthesized and tested against solid and hematological tumor cell lines. Compounds 4d-f were the most promising in cytotoxicity assays (IC50 ≤ 50 nM) vs. hematological cells and displayed moderate activity in solid tumor models (EC50 = 9.3-21.7 µM). Compound 4d potently inhibited multiple kinase targets of interest for anticancer effects, including JAK2, JAK3, HDAC1, and HDAC6. Molecular dynamics simulations showed that 4d has stable interactions with HDAC and members of the JAK family, with differences in the hinge binding energy conferring selectivity for JAK3 and JAK2 over JAK1. The kinase inhibition profile of compounds 4d-f allows selective cytotoxicity, with minimal effects on non-tumorigenic cells. Moreover, these compounds have favorable pharmacokinetic profiles, with high stability in human liver microsomes (e.g., see t1/2: >120 min for 4f), low intrinsic clearance, and lack of significant inhibition of four major CYP450 isoforms.

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Periodontal disease is a chronic condition characterized by bacterial adhesion, followed by biofilm formation, and subsequently by an inflammatory process that progresses to gingivitis and later to periodontitis. The variations in the oral microbiota have been associated with the progression of this disease. This study evaluated the alteration of the cultivable oral microbiota in dogs with different oral health status. Thirty dogs were selected and divided into three groups: healthy, gingivitis, and periodontitis. The collected oral samples were seeded, and colonies with distinct phenotypic characteristics were isolated and classified using sequencing of the 16S rRNA gene. The DNA sequences were aligned, and a phylogenetic tree was constructed. Simpson's diversity index was calculated, and a dissimilarity matrix based on the Jaccard similarity index was used to plot a principal coordinate analysis. A total of 119 bacteria with different colony morphologies were isolated and classified into 4 phyla, 29 genera, and 45 species based on phylogenetic analysis. The results indicated an increase in bacteria belonging to the Proteobacteria phylum and a less extended decrease in Actinobacteria, Firmicutes, and Bacteroidetes phyla in dogs with periodontal disease (gingivitis and periodontitis) compared to healthy dogs. Representatives of the genera Neisseria sp., Corynebacterium sp., Pasteurella sp., and Moraxella sp. increased through the worsening of the periodontal disease, while Staphylococcus sp. decreased. All groups exhibited moderate to high levels of biodiversity index, and the plotted PCoA show a clear separation in the oral microbiome of dogs with periodontitis compared to dogs with gingivitis and the healthy group.

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Palliative treatments for back pain usually include exercise, analgesics, physiotherapy, prostheses, and surgery in severe cases. Technologies for postural monitoring are growing, and they are important in preventing back pain and mitigating permanent damage. Remote work, especially after the COVID-19 pandemic, made people spend more time than usual in chairs and environments not certified by the health aspects of work. This research investigated through a Systematic Mapping Study (SMS) contributions in posture monitoring for healthcare in smart environments, including the different methods to obtain the posture, the limitations, and the target audience of the proposed models. The SMS was conducted in eight databases, including articles from January 2012 to March 2022. The initial search yielded 3161 articles, of which 34 were selected after applying the filtering criteria. Moreover, this study presents the challenges related to posture behavior monitoring, identifying studies and implementations that apply assistive technology for postural monitoring and improving the health and life of remote workers. In addition, three commercial postural devices are presented, and what challenges they currently face. Regarding healthcare, results showed a prevalence of using the Internet of Things (IoT) devices such as wireless sensor networks and inertial measurement unit (IMU) sensors. This article also proposes a taxonomy, showing the most used technologies and algorithms for improving posture, besides the posture-monitoring hierarchy classifying into three important branches: (a) Data Collect; (b) Data Transmission; and (c) Data Analysis.

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Abstract Objective: Galvanic vestibular stimulation has been evaluated in the context of vestibular rehabilitation. The objective was to identify evidence in the scientific literature about the clinical applications of galvanic vestibular stimulation. Methods: In this systematic review, the articles describing the applications of galvanic vestibular stimulation were extracted from PubMed, Web of Science, MEDLINE, Scopus, LILACS and SciELO databases. The survey was limited to articles published in English, Portuguese and Spanish. All the articles about the clinical applications of galvanic vestibular stimulation were compiled. Repeated articles in the databases, literature review articles, case reports, letters and editorials were excluded. The descriptors included: galvanic vestibular stimulation, postural balance, central nervous system diseases, vestibular diseases, spinal cord diseases and cognition. Results: The search strategy resulted in the initial selection of 994 articles; the reading of titles and abstracts was accomplished in 470 articles and the complete reading in 23 articles. Clinical applications of galvanic vestibular stimulation included Ménière's disease, vestibular neuritis, bilateral vestibular disorders, vestibular schwannoma, Parkinson's disease, ischemic central lesions, motor myelopathies, anxiety disorders, cognition and memory. Conclusion: Galvanic vestibular stimulation has been considered a potentially useful strategy for balance rehabilitation, since it has the effect of stimulating the central connections related to the postural balance, favoring new neuronal synapses that allow the partial or total recovery of postural imbalance.

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OBJECTIVE: Galvanic vestibular stimulation has been evaluated in the context of vestibular rehabilitation. The objective was to identify evidence in the scientific literature about the clinical applications of galvanic vestibular stimulation. METHODS: In this systematic review, the articles describing the applications of galvanic vestibular stimulation were extracted from PubMed, Web of Science, MEDLINE, Scopus, LILACS and SciELO databases. The survey was limited to articles published in English, Portuguese and Spanish. All the articles about the clinical applications of galvanic vestibular stimulation were compiled. Repeated articles in the databases, literature review articles, case reports, letters and editorials were excluded. The descriptors included: galvanic vestibular stimulation, postural balance, central nervous system diseases, vestibular diseases, spinal cord diseases and cognition. RESULTS: The search strategy resulted in the initial selection of 994 articles; the reading of titles and abstracts was accomplished in 470 articles and the complete reading in 23 articles. Clinical applications of galvanic vestibular stimulation included Ménière's disease, vestibular neuritis, bilateral vestibular disorders, vestibular schwannoma, Parkinson's disease, ischemic central lesions, motor myelopathies, anxiety disorders, cognition and memory. CONCLUSION: Galvanic vestibular stimulation has been considered a potentially useful strategy for balance rehabilitation, since it has the effect of stimulating the central connections related to the postural balance, favoring new neuronal synapses that allow the partial or total recovery of postural imbalance.

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Câncer é a denominação atribuída a um conjunto de doenças que são responsáveis pela segunda maior causa de morte no Brasil e no mundo. A quimioterapia figura entre uma das estratégias utilizadas para o tratamento e cura do câncer, sendo amplamente empregada em estratégias terapêuticas isoladas, ou em associação à radioterapia e cirurgia. A enzima histona desacetilase 6 (HDAC6) é responsável por desacetilar a cadeia lateral de N-acetillisinas em -tubulinas, desempanhando papel crítico na dinâmica do citoesqueleto celular, estando superexpressa em uma série de neoplasias. Neste sentido, na última década os receptores tirosina quinase (TQ) foram os principais alvos de fármacos aprovados para o tratamento do câncer e de doenças autoimunes e continuam atraindo a atenção de grupos de pesquisa dada a exorbitante diversidade do quinoma humano. É sabido que a monoterapia seja com inibidores de HDAC, seja com inibidores TQ, apresenta problemas de toxicidade, reações adversas, ineficácia, resistência e/ou recidiva. Diversos estudos relatam o desenvolvimento de inibidores duais de HDAC-TQ, almejando tanto a simplificação do tratamento, quanto sinergismo terapêutico e redução de efeitos adversos. Assim, o presente trabalho apresenta o planejamento, síntese e avaliação da citotoxicidade de inibidores duais, potencialmente seletivos para HDAC6 e receptores TQ. No total, 23 compostos foram sintetizados entre 2 a 4 etapas. Todos os compostos finais foram caracterizados por RMN (1H e 13C) e espectrometria de massas de alta resolução (HRMS). A citotoxicidade foi determinada pelo ensaio de MTT, em linhagens derivadas de tumores sólidos (HCT116 e MCF-7) e hematológicos (Jurkat e Namalwa). Os compostos apresentaram citotoxicidade em concentrações micro e nanomolares em todas as linhagens testadas, sendo que a linhagem MCF-7 foi a mais resistente à ação dos compostos, e as linhagens hematológicas foram as mais sensíveis. Os inibidores 4d-f foram os mais ativos na triagem por MTT, com IC50 iguais a 20, 30 e 50 nM, respectivamente, em células Jurkat. Estudos mecanísticos do efeito citotóxico indicaram que os compostos 4d-f exercem atividade de forma tempo-dependente, e majoritariamente por ação antiproliferativa, embora estímulos apoptóticos também tenham sido observados nos estudos. Simulações de ancoramento molecular (docking) e de relação entre as estruturas químicas dos compostos e suas respectivas atividades biológicas (REA) permitiram identificar padrões moleculares, propriedades físico-químicas e eletrônicas que potencialmente possuem relação com a atividade biológica dos compostos, permitindo futuras otimizações do arcabouço molecular desta série de compostos. Tomados em conjunto, os resultados deste trabalho revelam o potencial terapêutico de inibidores duais de HDAC6-TQ. Notadamente, os compostos apresentados aqui podem ser os primeiros potenciais inibidores duais de HDAC6-TQ a serem reportados na literatura

Cancer is the name of a series of diseases that are the second main cause of death in Brazil and worldwide. Chemotherapy is one of the main strategies to treat and cure cancer, and has been widely applied as a single therapeutic agent, and in association with radiotherapy and surgery. Histone deacetylase 6 (HDAC6) deacetylates N-acetyllysine side chains of tubulin, playing crucial role on cytoskeletal dynamics, and could be overexpressed in several cancers. Tyrosine kinase receptors (TK) have been the main targets of FDA-approved drugs through the last decade for both cancer and autoimmune diseases, and have been attracting special attention of research groups due to the exorbitant diversity of the human kinome. It is known that either HDAC or TK single therapy have toxicity issues, adverse effects, inefficacy, resistance and/or recidive. Therefore, many studies report the design of HDAC-TK dual inhibitors aiming simpler treatments, synergism of action and side effects reduction. Herein, the design, synthesis and cytotoxic evaluation of dual and selective HDAC6-TK inhibitors are presented. A total of 23 compounds were designed and synthesized through 2 to 4 steps. All final compounds were characterized by 1H/13C NMR and high-resolution mass spectrometry (HRMS). The cytotoxicity of compounds was determined by MTT assay for both solid (HCT116 and MCF-7 cells) and hematological cancers (Jurkat and Namalwa cells). Compounds exhibited micro and nanomolar ranges of cytotoxicity for all cell lines tested. MCF-7 cells were the most resistant against the treatment, and hematological cells were more susceptible to the cytotoxic effect of the compounds. Compounds 4d-f were the most actives in the MTT screening against Jurkat cells (IC50 = 20, 30 and 50 nM, respectively). Mechanistic studies regarding the cytotoxic effects of 4d-f indicated that the compounds induced cell death in a time-dependent manner mainly via cytostatic activity even though apoptotic stimuli were observed also. Molecular docking and structure-activity relationships (SARs) allowed the identification of molecular patterns, and physicochemical and electronic properties that potentially modulate the biological activity of these compounds, allowing further optimizations of the molecular scaffold for these series of compounds. Taken together, the results of this study reveal the therapeutic potential of HDAC6-TK dual inhibitors. Noteworthy, the compounds reported herein could be the first HDAC6-TK dual inhibitors ever reported in literature

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New ecosystems are being actively mined for new bioactive compounds. Because of the large amount of unexplored biodiversity, bacteria from marine environments are especially promising. Further, host-associated microbes are of special interest because of their low toxicity and compatibility with host health. Here, we identified and characterized biosynthetic gene clusters encoding antimicrobial compounds in host-associated enterococci recovered from fecal samples of wild marine animals remote from human-affected ecosystems. Putative biosynthetic gene clusters in the genomes of 22 Enterococcus strains of marine origin were predicted using antiSMASH5 and Bagel4 bioinformatic software. At least one gene cluster encoding a putative bioactive compound precursor was identified in each genome. Collectively, 73 putative antimicrobial compounds were identified, including 61 bacteriocins (83.56%), 10 terpenes (13.70%), and 2 (2.74%) related to putative nonribosomal peptides (NRPs). Two of the species studied, Enterococcus avium and Enterococcus mundtti, are rare causes of human disease and were found to lack any known pathogenic determinants but yet possessed bacteriocin biosynthetic genes, suggesting possible additional utility as probiotics. Wild marine animal-associated enterococci from human-remote ecosystems provide a potentially rich source for new antimicrobial compounds of therapeutic and industrial value and potential probiotic application.

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BACKGROUND: Tuberculosis (TB) has been a challenging disease worldwide, especially for the neglected poor populations. Presently, there are approximately 2 billion people infected with TB worldwide and 10 million people in the world fell ill with active TB, leading to 1.5 million deaths. INTRODUCTION: The classic treatment is extensive and the drug- and multi-drug resistance of Mycobacterium tuberculosis has been a threat to the efficacy of the drugs currently used. Therefore, the rational design of new anti-TB candidates is urgently needed. METHODS: With the aim of contributing to face this challenge, 78 compounds have been proposed based on SBDD (Structure-Based Drug Design) strategies applied to target the M. tuberculosis phosphopantetheine adenylyltransferase (MtPPAT) enzyme. Ligand-Based Drug Design (LBDD) strategies were also used for establishing Structure-Activity Relationships (SAR) and for optimizing the structures. MtPPAT is important for the biosynthesis of coenzyme A (CoA) and it has been studied recently toward the discovery of new inhibitors. RESULTS: After docking simulations and enthalpy calculations, the interaction of selected compounds with MtPPAT was found to be energetically favorable. The most promising compounds were then synthesized and submitted to anti-M. tuberculosis and MtPPAT inhibition assays. CONCLUSION: One of the compounds synthesized (MCP163), showed the highest activity in both of these assays.

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