Protocol for in silico characterization of natural-based molecules as quorum-sensing inhibitors.

The search and development of new quorum-sensing (QS) inhibitors are ongoing processes for biofilm control. Here, we present a protocol for in silico characterization of natural-based molecules as QS inhibitors. We describe steps for preparing models of protein receptors for virtual screening. We then detail procedures for construction and virtual screening of phytochemical libraries and hit picking to be experimentally validated by in vitro assays. This protocol allows exploration of a broad range of potential inhibitors for a specific target. For complete details on the use and execution of this protocol, please refer to Fernandes et al.1.

In silico-guided discovery and in vitro validation of novel sugar-tethered lysinated carbon nanotubes for targeted drug delivery of doxorubicin.

CONTEXT: Multiwalled carbon nanotubes (MWCNTs) functionalized with lysine via 1,3-dipolar cycloaddition and conjugated to galactose or mannose are potential nanocarriers that can effectively bind to the lectin receptor in MDA-MB-231 or MCF-7 breast cancer cells. In this work, a method based on molecular dynamics (MD) simulation was used to predict the interaction of these functionalized MWCNTs with doxorubicin and obtain structural evidence that allows a better understanding of the drug loading and release process. The MD simulations showed that while doxorubicin only interacted with pristine MWCNTs through π-π stacking interactions, functionalized MWCNTs were also able to establish hydrogen bonds, suggesting that the functionalized groups improve doxorubicin loading. Moreover, the elevated adsorption levels observed for functionalized nanotubes further support this enhancement in loading efficiency. MD simulations also shed light on the intratumoral pH-specific release of doxorubicin from functionalized MWCNTs, which is induced by protonation of the daunosamine moiety. The simulations show that this change in protonation leads to a lower absorption of doxorubicin to the MWCNTs. The MD studies were then experimentally validated, where functionalized MWCNTs showed improved dispersion in aqueous medium compared to pristine MWCNTs and, in agreement with the computational predictions, increased drug loading capacity. Doxorubicin-loaded functionalized MWCNTs demonstrated specific release of doxorubicin in tumor microenvironment (pH = 5.0) with negligible release in the physiological pH (pH = 7.4). Furthermore, doxorubicin-free MWNCT nanoformulations exhibited insignificant cytotoxicity. The experimental studies yielded nearly identical results to the MD studies, underlining the usefulness of the method. Our functionalized MWCNTs represent promising non-toxic nanoplatforms with enhanced aqueous dispersibility and the potential for conjugation with ligands for targeted delivery of anti-cancer drugs to breast cancer cells. METHODS: The computational model of a pristine carbon nanotube was created with the buildCstruct 1.2 Python script. The lysinated functionalized groups were added with PyMOL and VMD. The carbon nanotubes and doxorubicin molecules were parameterized using the general AMBER force field, and RESP charges were determined using Gaussian 09. Molecular dynamics simulations were carried out with the AMBER 20 software package. Adsorption levels were calculated using the water-shell function of cpptraj. Cytotoxicity was evaluated via a MTT assay using MDA-MB-231 and MCF-7 breast cancer cells. Drug uptake of doxorubicin and doxorubicin-loaded MWCNTs was measured by fluorescence microscopy.

Biostimulant Response of Foliar Application of Rare Earth Elements on Physiology, Growth, and Yield of Rice.

Rare earth elements (REEs) have been intentionally used in Chinese agriculture since the 1980s to improve crop yields. Around the world, REEs are also involuntarily applied to soils through phosphate fertilizers. These elements are known to alleviate damage in plants under abiotic stresses, yet there is no information on how these elements act in the physiology of plants. The REE mode of action falls within the scope of the hormesis effect, with low-dose stimulation and high-dose adverse reactions. This study aimed to verify how REEs affect rice plants' physiology to test the threshold dose at which REEs could act as biostimulants in these plants. In experiment 1, 0.411 kg ha-1 (foliar application) of a mixture of REE (containing 41.38% Ce, 23.95% La, 13.58% Pr, and 4.32% Nd) was applied, as well as two products containing 41.38% Ce and 23.95% La separately. The characteristics of chlorophyll a fluorescence, gas exchanges, SPAD index, and biomass (pot conditions) were evaluated. For experiment 2, increasing rates of the REE mix (0, 0.1, 0.225, 0.5, and 1 kg ha-1) (field conditions) were used to study their effect on rice grain yield and nutrient concentration of rice leaves. Adding REEs to plants increased biomass production (23% with Ce, 31% with La, and 63% with REE Mix application) due to improved photosynthetic rate (8% with Ce, 15% with La, and 27% with REE mix), favored by the higher electronic flow (photosynthetic electron transport chain) (increase of 17%) and by the higher Fv/Fm (increase of 14%) and quantum yield of photosystem II (increase of 20% with Ce and La, and 29% with REE Mix), as well as by increased stomatal conductance (increase of 36%) and SPAD index (increase of 10% with Ce, 12% with La, and 15% with REE mix). Moreover, adding REEs potentiated the photosynthetic process by increasing rice leaves' N, Mg, K, and Mn concentrations (24-46%). The dose for the higher rice grain yield (an increase of 113%) was estimated for the REE mix at 0.72 kg ha-1.

Analysis of hospital dental care for patients with special needs in Brazil.

This analytical cross-sectional study aimed to analyze the access of patients with special needs (PSN) in Brazilian municipalities to hospital dental care of the Unified Health System (Sistema Único de Saúde - SUS), based on data from the Hospital Information System of the Unified Health System (Sistema de Informações Hospitalares do SUS- SIH/SUS - SIH), from 2010 to 2018. The Kolmogorov-Smirnov normality test was performed; the Poisson regression was used to verify factors associated with the variable total number of hospitalization authorizations with the main procedure of dental treatment for PSN ("Total de Autorizações de Internação Hospitalar" - AIH), the Spearman correlation test with a significance level of 5% was used to characterize the relationships between the Municipal Human Development Index per municipality - (Índice de Desenvolvimento Humano Municipal - HDI) and the Oral Health Coverage in the Family Health Strategy by municipality (Cobertura de saúde bucal na estratégia saúde da família por município - SBSF Coverage), and the relationship of the AIH with SBSF Coverage. A total of 127,691 procedures were performed, of which 71,517 (56%) were clinical procedures, such as restorations, endodontic treatments, supra and subgingival scaling, among others. Municipalities in the Midwest (PR=5.117) and Southeast (RP = 4.443) regions had more precedures than the others. A weak correlation was found between AIH and SBSF Coverage (r = -0.2, p < 0.001) and HDI and SBSF Coverage (r = -0.074, p < 0.001). Population size, region, health coverage, oral hygiene, and number of dentists in hospitals affected the availability of dental procedures in PSN.

How different attributes are weighted in professionals' decision-making in Pediatric Dentistry-a protocol for guiding discrete choice experiment focused on shortening the evidence-based practice implementation for dental care.

BACKGROUND: Important evidence has been constantly produced and needs to be converted into practice. Professional consumption of such evidence may be a barrier to its implementation. Then, effective implementation of evidence-based interventions in clinical practice leans on the understanding of how professionals value attributes when choosing between options for dental care, permitting to guide this implementation process by maximizing strengthens and minimizing barriers related to that. METHODS: This is part of a broader project investigating the potential of incorporating scientific evidence into clinical practice and public policy recommendations and guidelines, identifying strengths and barriers in such an implementation process. The present research protocol comprises a Discrete Choice Experiment (DCE) from the Brazilian oral health professionals' perspective, aiming to assess how different factors are associated with professional decision-making in dental care, including the role of scientific evidence. Different choice sets will be developed, either focusing on understanding the role of scientific evidence in the professional decision-making process or on understanding specific attributes associated with different interventions recently tested in randomized clinical trials and available as newly produced scientific evidence to be used in clinical practice. DISCUSSION: Translating research into practice usually requires time and effort. Shortening this process may be useful for faster incorporation into clinical practice and beneficial to the population. Understanding the context and professionals' decision-making preferences is crucial to designing more effective implementation and/or educational initiatives. Ultimately, we expect to design an efficient implementation strategy that overcomes threats and potential opportunities identified during the DCEs, creating a customized structure for dental professionals. TRIAL REGISTRATION: https://osf.io/bhncv .

Orthodontics in the oral health care network of the Unified Health System (SUS).

This observational study aimed to describe and analyze data from two external evaluations of the National Program for Improving Access to and Quality of Dental Specialty Centers (PMAQ CEO), held in 2014 and 2018 in Brazil, which evaluated Dental Specialty Centers (CEO) using a national and census approach. We selected questions through a search in the microdata of the first and second evaluations. The groups were analyzed independently. To compare the groups, nonparametric tests were performed (Mann Whitney U). The formulated hypotheses were: there would be no differences between the data of these groups (h0) and there would be differences between the data of these groups (h1). For qualitative nominal variables, frequency distribution was verified and association tests were performed (chi-square test). The significance level for this study was set at 5%. We observed that orthodontic treatments were found in about 13% of the CEO. Regarding human resources, most professionals were specialists or had MSc or PhD degrees; were civil servants; had been hired by direct administration; or had been hired via public tender. Regarding the work process and inclusion of the CEO in the health care network, we observed a greater number of services that use single and electronic medical records, greater presence of services monitoring and analyzing goals, greater knowledge about monthly average of absenteeism (for 2018); and larger number of services with referrals from primary health care centers (for 2014). Expanding the view on orthodontics and including preventive, interceptive, and corrective treatments at different points in health care networks are essential strategies for achieving comprehensive care in universal health systems.

Orthodontics in the oral health care network of the Unified Health System (SUS)

Abstract This observational study aimed to describe and analyze data from two external evaluations of the National Program for Improving Access to and Quality of Dental Specialty Centers (PMAQ CEO), held in 2014 and 2018 in Brazil, which evaluated Dental Specialty Centers (CEO) using a national and census approach. We selected questions through a search in the microdata of the first and second evaluations. The groups were analyzed independently. To compare the groups, nonparametric tests were performed (Mann Whitney U). The formulated hypotheses were: there would be no differences between the data of these groups (h0) and there would be differences between the data of these groups (h1). For qualitative nominal variables, frequency distribution was verified and association tests were performed (chi-square test). The significance level for this study was set at 5%. We observed that orthodontic treatments were found in about 13% of the CEO. Regarding human resources, most professionals were specialists or had MSc or PhD degrees; were civil servants; had been hired by direct administration; or had been hired via public tender. Regarding the work process and inclusion of the CEO in the health care network, we observed a greater number of services that use single and electronic medical records, greater presence of services monitoring and analyzing goals, greater knowledge about monthly average of absenteeism (for 2018); and larger number of services with referrals from primary health care centers (for 2014). Expanding the view on orthodontics and including preventive, interceptive, and corrective treatments at different points in health care networks are essential strategies for achieving comprehensive care in universal health systems.

Analysis of hospital dental care for patients with special needs in Brazil

Abstract This analytical cross-sectional study aimed to analyze the access of patients with special needs (PSN) in Brazilian municipalities to hospital dental care of the Unified Health System (Sistema Único de Saúde - SUS), based on data from the Hospital Information System of the Unified Health System (Sistema de Informações Hospitalares do SUS- SIH/SUS - SIH), from 2010 to 2018. The Kolmogorov-Smirnov normality test was performed; the Poisson regression was used to verify factors associated with the variable total number of hospitalization authorizations with the main procedure of dental treatment for PSN ("Total de Autorizações de Internação Hospitalar" - AIH), the Spearman correlation test with a significance level of 5% was used to characterize the relationships between the Municipal Human Development Index per municipality - (Índice de Desenvolvimento Humano Municipal - HDI) and the Oral Health Coverage in the Family Health Strategy by municipality (Cobertura de saúde bucal na estratégia saúde da família por município - SBSF Coverage), and the relationship of the AIH with SBSF Coverage. A total of 127,691 procedures were performed, of which 71,517 (56%) were clinical procedures, such as restorations, endodontic treatments, supra and subgingival scaling, among others. Municipalities in the Midwest (PR=5.117) and Southeast (RP = 4.443) regions had more precedures than the others. A weak correlation was found between AIH and SBSF Coverage (r = -0.2, p < 0.001) and HDI and SBSF Coverage (r = -0.074, p < 0.001). Population size, region, health coverage, oral hygiene, and number of dentists in hospitals affected the availability of dental procedures in PSN.

Atraumatic Restorative Treatment (ART) as Public Policy: a Scoping Review / O Tratamento Restaurador Atraumático (ART) como Política Pública: uma Revisão de Escopo

This scoping review aimed to identify, describe, and analyze the use of Atraumatic Restorative Treatment (ART) as public policy. Inclusion criteria: studies on public oral health policies; dental caries; ART. Exclusion criteria: clinical studies; specific interventions; studies that report public policies that do not use ART as a strategy for caries treatment. The search was conducted in PubMed, BVS, Epistemonikos, Health Systems Evidence, and Rxforchange. The selection process and data extraction were performed by two authors independently according to the stages and categories of a conceptual framework. Of the 2253 eligible articles, 139 were duplicates, and 1680 were not included after reading the title and abstract. After assessing the full text, 414 articles were excluded. Twenty articles were included. Nineteen were conducted in nine countries (South Africa, Bolivia, Cambodia, Egypt, Mexico, Tanzania, East Timor, Tunisia, and Zimbabwe), and one in the Americas. The studies reported high prevalence of dental caries and lack of access to restorative procedures in health services as common problems. Policy developments followed a similar process, with the presence of governments, conceptual use of scientific evidence, and induction by the World Health Organization. Regarding implementation barriers, the included studies mentioned the lack of supplies and lack of induction by managers,while in relation to the facilitators, permanent education and professional practice were mentioned. Cohort studies have shown a survival rate greater than 80% after one year of follow up of the restorations performed. The findings of this review indicate that the use of ART in public policies is promising, however, its use is still in an early stage. (AU)

Esta revisão de escopo teve como objetivo identificar, descrever e analisar o uso do Tratamento Restaurador Atraumático (ART) como política pública. Critérios de inclusão: estudos sobre políticas públicas de saúde bucal; cáries dentárias; ART. Critérios de exclusão: estudos clínicos; intervenções específicas; estudos que relatam políticas públicas que não utilizam o ART como estratégia para o tratamento de cárie. A pesquisa foi realizada no PubMed, BVS, Epistemonikos, Health Systems Evidence e Rxforchange. O processo de seleção e extração de dados foram realizados por dois autores, de forma independente, de acordo com as etapas e categorias de um quadro conceitual. Dos 2.253 artigos elegíveis, 139 eram duplicados e 1.680 não foram incluídos após a leitura do título e do resumo. Após avaliação do texto completo, foram excluídos 414 artigos. Vinte artigos foram incluídos. Dezenove foram realizados em nove países (África do Sul, Bolívia, Camboja, Egito, México, Tanzânia, Timor Leste, Tunísia e Zimbábue) e um nas Américas. Os estudos relataram alta prevalência de cárie dentária e falta de acesso a procedimentos restauradores nos serviços de saúde como problemas comuns. Os desenvolvimentos de políticas seguiram um processo semelhante, com a presença de governos, uso conceitual de evidências científicas e indução da Organização Mundial da Saúde. Quanto às barreiras de implementação, foram mencionadas a falta de insumos e a falta de indução por parte dos gestores. Quanto aos facilitadores, foram citados a educação permanente e a prática profissional. Estudos de coorte mostraram sobrevida superior a 80% após um ano de acompanhamento. Os achados desta revisão indicam que a utilização da ART nas políticas públicas é promissora, porém, sua utilização ainda é incipiente. (AU)

Sodium Selenate, Potassium Hydroxy-Selenide, Acetylselenide and Their Effect on Antioxidant Metabolism and Plant Nutrition and Yield in Sorghum Genotypes.

Agronomic biofortification with selenium (Se) effectively reduces hidden hunger and increases the nutritional intake of Se in people and animals. Because sorghum is a staple diet for millions of people and is used in animal feed, it becomes a crop with biofortification potential. Consequently, this study aimed to compare organoselenium compounds with selenate, which is effective in numerous crops, and to assess grain yield, the effect in the antioxidant system, and macronutrient/micronutrient contents of different sorghum genotypes treated with Se, via foliar spray. The trials used a 4 × 8 factorial design, with four Se sources (control-without Se supply, sodium selenate, potassium hydroxy-selenide, acetylselenide) and eight genotypes (BM737, BRS310, Enforcer, K200, Nugrain320, Nugrain420, Nugrain430, and SHS410). The Se rate used was 0.125 mg plant-1. All genotypes reacted effectively to foliar fertilization with Se through sodium selenate. In this experiment, potassium hydroxy-selenide and acetylselenide showed low Se levels and lower Se uptake and absorption efficiency than selenate. Selenium fertilization increased grain yield and altered lipid peroxidation by malondialdehyde content, hydrogen peroxide content, catalase activity, ascorbate peroxidase, superoxide dismutase, and macronutrients and micronutrients content of the studied genotypes. In sum, biofortification with selenium led to an overall yield increase of sorghum plants and supplementation with selenium through sodium selenate was more efficient than organoselenium compounds, yet acetylselenide had a positive effect on the antioxidant system. Sorghum can be effectively biofortified through the foliar application of sodium selenate; however, studying the interaction between organic and inorganic Se compounds in plants is necessary.

Synthesis of Novel Diketopyrrolopyrrole-Rhodamine Conjugates and Their Ability for Sensing Cu2+ and Li.

The search for accurate and sensitive methods to detect chemical substances, namely cations and anions, is urgent and widely sought due to the enormous impact that some of these chemical species have on human health and on the environment. Here, we present a new platform for the efficient sensing of Cu2+ and Li+ cations. For this purpose, two novel photoactive diketopyrrolopyrrole-rhodamine conjugates were synthesized through the condensation of a diketopyrrolopyrrole dicarbaldehyde with rhodamine B hydrazide. The resulting chemosensors 1 and 2, bearing one or two rhodamine hydrazide moieties, respectively, were characterized by 1H and 13C NMR and high-resolution mass spectrometry, and their photophysical and ion-responsive behaviours were investigated via absorption and fluorescence measurements. Chemosensors 1 and 2 displayed a rapid colorimetric response upon the addition of Cu2+, with a remarkable increase in the absorbance and fluorescence intensities. The addition of other metal ions caused no significant effects. Moreover, the resulting chemosensor-Cu2+ complexes revealed to be good probes for the sensing of Li+ with reversibility and low detection limits. The recognition ability of the new chemosensors was investigated by absorption and fluorescence titrations and competitive studies.

The major role of junctional diversity in the horse antibody repertoire.

The antibody repertoire (Rep-seq) sequencing revolutionized the diversity of antigen B cell receptor studies, allowing deep and quantitative analysis to decipher the role of adaptive immunity in health and disease. Particularly, horse (Equus caballus) polyclonal antibodies have been produced and used since the century XIX to treat and prophylaxis diphtheria, tuberculosis, tetanus, pneumonia, and, more recently, COVID-19. However, our knowledge about the horse B cell receptors repertories is minimal. We present a deep horse antibody heavy chain repertoire (IGH) characterization of non-infected horses using NGS (Next generation sequencing). This study obtained a mean of 248,169 unique IgM clones and 66,141 unique IgG clones from four domestic adult horses. Rarefaction analysis showed sequence coverage was between 52 % and 82 % in IgM and IgG isotypes. We observed that besides horses antibody can use all functional IGHV genes, around 80 % of their antibodies use only three IGHV gene segments, and around 55 % use only one IGHJ gene segment. This limited VJ diversity seems to be compensated by the junctional diversity of these antibodies. We observed that the junctional diversity in horse antibodies is widespread, present in more than 90 % of horse antibodies. Besides this, the length of this region seems to be higher in horse antibodies than in other species. N1 and N2 nucleotides addition range from 0 to 111 nucleotides. In addition, around 45 % of the antibody clones have more than ten nucleotides in both the N1 and N2 junction regions. This diversity mechanism may be one of the most important in providing variability to the equine antibody repertoire. This study provides new insights regarding horse antibody composition, diversity generation, and particularities compared to other species, such as the frequency and length of N nucleotide addition. This study also points out the urgent need to better characterize TdT in horses and other species to better understand antibody repertoire characteristics.

Selection of Bis-Indolyl Pyridines and Triphenylamines as New Inhibitors of SARS-CoV-2 Cellular Entry by Modulating the Spike Protein/ACE2 Interfaces.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the infectious agent that has caused the current coronavirus disease (COVID) pandemic. Viral infection relies on the viral S (spike) protein/cellular receptor ACE2 interaction. Disrupting this interaction would lead to early blockage of viral replication. To identify chemical tools to further study these functional interfaces, 139,146 compounds from different chemical libraries were screened through an S/ACE2 in silico virtual molecular model. The best compounds were selected for further characterization using both cellular and biochemical approaches, reiterating SARS-CoV-2 entry and the S/ACE2 interaction. We report here two selected hits, bis-indolyl pyridine AB-00011778 and triphenylamine AB-00047476. Both of these compounds can block the infectivity of lentiviral vectors pseudotyped with the SARS-CoV-2 S protein as well as wild-type and circulating variant SARS-CoV-2 strains in various human cell lines, including pulmonary cells naturally susceptible to infection. AlphaLISA and biolayer interferometry confirmed a direct inhibitory effect of these drugs on the S/ACE2 association. A specific study of the AB-00011778 inhibitory properties showed that this drug inhibits viral replication with a 50% effective concentration (EC50) between 0.1 and 0.5 µM depending on the cell lines. Molecular docking calculations of the interaction parameters of the molecules within the S/ACE2 complex from both wild-type and circulating variants of the virus showed that the molecules may target multiple sites within the S/ACE2 interface. Our work indicates that AB-00011778 constitutes a good tool for modulating this interface and a strong lead compound for further therapeutic purposes.

Investigating spray flames for nanoparticle synthesis via tomographic imaging using multi-simultaneous measurements (TIMes) of emission.

Tomographic imaging using multi-simultaneous measurements (TIMes) of spontaneous light emission was performed on various operating conditions of the SpraySyn burner to analyse the flame morphology and its potential impact on spray flame pyrolysis. Concurrent instantaneous and time-averaged three-dimensional measurements of CH* chemiluminescence (flame front indicator) and atomic Na emission from NaCl dissolved in the injected combustible liquid (related to hot burnt products of the spray flame) were reconstructed employing a 29-camera setup. Overlapping regions of CH* and Na are presented using isosurface visualisation, local correlation coefficient fields and joint probability distributions. The instantaneous results reveal the complex nature of the reacting flow and regions of interaction between the flame front with the hot gases that originate from the spray stream. The averaged reconstructions show that the spray flames tested are slightly asymmetric near the burner exit but develop into symmetric bell-shaped distributions at downstream locations. The changes in the flame structure for different operating conditions are analysed in light of previous studies, helping in the better understanding of the nanoparticle synthesis process. Furthermore, the importance of using measurements from two views for significantly improved alignment of the burner based on the originally proposed procedure are discussed in light of the reconstructions. This is an important aspect since the SpraySyn is intended for use as a well-defined standardised burner for nanoparticle synthesis, which is being investigated numerically and experimentally across different research groups.

An ecotoxicological approach can complement the assessment of natural waters from Portuguese reservoirs?

Within the scope of the European Water Framework Directive (WFD), the scientific community recognized clear opportunities to take advantage of the use of ecotoxicological tools in water quality assessments. In this perspective, bioassays and biomarkers were suggested to contribute to the integration of the chemical and biological conditions, and thus to provide an overall insight into the quality of a water body. This study aimed to assess whether current bioassays as feeding rate assays with Daphnia longispina and growth inhibition assays with Lemna minor are suitable to detect potential ecotoxicity, using waters from Portuguese reservoirs. Several sampling sites were defined in reservoirs (Miranda, Pocinho, and Alqueva). The samplings were conducted in autumn of 2018 and spring of 2019. Total chlorophyll, lipid peroxidation, and proline content were also evaluated in L. minor. Results demonstrated that D. longispina showed some sensitivity to water treatments; however, the results were difficult to interpret since no reason or trend can be accurate. All parameters of L. minor did not show sensitivity to detect potential ecotoxicological risks associated with natural water understudy, since no discrimination among the water treatments was recorded. However, biomarkers/bioassays proved to be concordant to each other. Under the conditions evaluated here (reservoirs and sampling periods), the biological responses observed were not consistent, clear, and coherent with the physical-chemical parameters and chemical analyses performed, suggesting that the ecotoxicological tools selected were not sensitive to assess water quality in this type of ecosystems. In this sense, species of different trophic levels are recommended for ecotoxicological analyses due to differences in species sensitivities.

O processo de trabalho em saúde bucal coletiva em tempos de pandemia: a contribuição da teleducação com a teleodontologia / The work process in collective oral health in times of a pandemic: the contribution of tele-education with teledentistry

A pandemia da COVID-19 impôs ações assertivas em todos os níveis da sociedade. Aqui se relata o apoio emergencial na Resposta Rápida do Núcleo de Evidências e Análises Econômicas da Faculdade de Odontologia da Universidade de São Paulo (EvipOralHealth) para a coordenadoria estadual de saúde bucal de São Paulo, em prol da tomada de decisão e ressignificação do processo de trabalho. Foram implementadas duas estratégias de teleodontologia para a educação permanente (EP) dos trabalhadores de saúde bucal: 1. Lives com pesquisadores, estudantes, gestores e trabalhadores das diversas áreas da saúde pública e da Odontologia para estabelecer marcos teóricos; 2. Ambulatórios virtuais - via webconferência. Reuniu-se gestores e trabalhadores para a condução de diálogos de políticas sobre o dia a dia do enfrentamento e de adaptações e condições de trabalho de cada região. A experiência revela a importância da relação ensino-serviço-comunidade efetiva, pautada na tradução do conhecimento e na construção de espaços de troca possibilitando a implementação de práticas, programas e políticas. Precisamos repensar as estratégias de EP, sermos mais ágeis, mais flexíveis, menos acadêmicos e capazes de adaptar conteúdos e formatos às necessidades. A teleodontologia e a teleducação podem conferir escala e fazer chegar mais facilmente o conhecimento aos que necessitam.

Acute Whole-Body Vibration Exercise Promotes Favorable Handgrip Neuromuscular Modifications in Rheumatoid Arthritis: A Cross-Over Randomized Clinical.

OBJECTIVE: Rheumatoid arthritis (RA) causes progressive changes in the musculoskeletal system compromising neuromuscular control especially in the hands. Whole-body vibration (WBV) could be an alternative for the rehabilitation in this population. This study investigated the immediate effect of WBV while in the modified push-up position on neural ratio (NR) in a single session during handgrip strength (HS) in women with stable RA. METHODS: Twenty-one women with RA (diagnosis of disease: ±8 years, erythrocyte sedimentation rate: ±24.8, age: 54± 11 years, BMI: 28 ± 4 kg·m-2) received three experimental interventions for five minutes in a randomized and balanced cross-over order: (1) control-seated with hands at rest, (2) sham-push-up position with hands on the vibration platform that remained disconnected, and (3) vibration-push-up position with hands on the vibration platform turned on (45 Hz, 2 mm, 159.73 m·s-2). At the baseline and immediately after the three experimental interventions, the HS, the electromyographic records (EMGrms), and range of motion (ROM) of the dominant hand were measured. The NR, i.e., the ratio between EMGrms of the flexor digitorum superficialis (FDS) muscle and HS, was also determined. The lower NR represented the greater neuromuscular efficiency (NE). RESULTS: The NR was similar at baseline in the three experimental interventions. Despite the nonsignificance of within-interventions (p = 0.0611) and interaction effect (p = 0.1907), WBV exercise reduced the NR compared with the sham and control (p = 0.0003, F = 8.86, η 2 = 0.85, power = 1.00). CONCLUSION: Acute WBV exercise under the hands promotes neuromuscular modifications during the handgrip of women with stable RA. Thus, acute WBV exercise may be used as a preparatory exercise for the rehabilitation of the hands in this population. This trial is registered with trial registration 2.544.850 (ReBEC-RBR-2n932c).

In Silico Identification of Possible Inhibitors for Protein Kinase B (PknB) of Mycobacterium tuberculosis.

With tuberculosis still being one of leading causes of death in the world and the emergence of drug-resistant strains of Mycobacterium tuberculosis (Mtb), researchers have been seeking to find further therapeutic strategies or more specific molecular targets. PknB is one of the 11 Ser/Thr protein kinases of Mtb and is responsible for phosphorylation-mediated signaling, mainly involved in cell wall synthesis, cell division and metabolism. With the amount of structural information available and the great interest in protein kinases, PknB has become an attractive target for drug development. This work describes the optimization and application of an in silico computational protocol to find new PknB inhibitors. This multi-level computational approach combines protein-ligand docking, structure-based virtual screening, molecular dynamics simulations and free energy calculations. The optimized protocol was applied to screen a large dataset containing 129,650 molecules, obtained from the ZINC/FDA-Approved database, Mu.Ta.Lig Virtual Chemotheca and Chimiothèque Nationale. It was observed that the most promising compounds selected occupy the adenine-binding pocket in PknB, and the main interacting residues are Leu17, Val26, Tyr94 and Met155. Only one of the compounds was able to move the active site residues into an open conformation. It was also observed that the P-loop and magnesium position loops change according to the characteristics of the ligand. This protocol led to the identification of six compounds for further experimental testing while also providing additional structural information for the design of more specific and more effective derivatives.

Can a Single Trial of a Thoracolumbar Myofascial Release Technique Reduce Pain and Disability in Chronic Low Back Pain? A Randomized Balanced Crossover Study.

Although manual therapy for pain relief has been used as an adjunct in treatments for chronic low back pain (CLBP), there is still the belief that a single session of myofascial release would be effective. This study was a crossover clinical trial aimed to investigate whether a single session of a specific myofascial release technique reduces pain and disability in subjects with CLBP. 41 participants over 18 years old were randomly enrolled into 3 situations in a balanced and crossover manner: experimental, placebo, and control. The subjects underwent a single session of myofascial release on thoracolumbar fascia and the results were compared with the control and placebo groups. The outcomes, pain and functionality, were evaluated using the numerical pain rating scale (NPRS), pressure pain threshold (PPT), and Oswestry Disability Index (ODI). There were no effects between-tests, within-tests, nor for interaction of all the outcomes, i.e., NPRS (η 2 = 0.32, F = 0.48, p = 0.61), PPT (η2 = 0.73, F = 2.80, p = 0.06), ODI (η2 = 0.02, F = 0.02, p = 0.97). A single trial of a thoracolumbar myofascial release technique was not enough to reduce pain intensity and disability in subjects with CLBP.

Identification of New Potential Inhibitors of Quorum Sensing through a Specialized Multi-Level Computational Approach.

Biofilms are aggregates of microorganisms anchored to a surface and embedded in a self-produced matrix of extracellular polymeric substances and have been associated with 80% of all bacterial infections in humans. Because bacteria in biofilms are less amenable to antibiotic treatment, biofilms have been associated with developing antibiotic resistance, a problem that urges developing new therapeutic options and approaches. Interfering with quorum-sensing (QS), an important process of cell-to-cell communication by bacteria in biofilms is a promising strategy to inhibit biofilm formation and development. Here we describe and apply an in silico computational protocol for identifying novel potential inhibitors of quorum-sensing, using CviR-the quorum-sensing receptor from Chromobacterium violaceum-as a model target. This in silico approach combines protein-ligand docking (with 7 different docking programs/scoring functions), receptor-based virtual screening, molecular dynamic simulations, and free energy calculations. Particular emphasis was dedicated to optimizing the discrimination ability between active/inactive molecules in virtual screening tests using a target-specific training set. Overall, the optimized protocol was used to evaluate 66,461 molecules, including those on the ZINC/FDA-Approved database and to the Mu.Ta.Lig Virtual Chemotheca. Multiple promising compounds were identified, yielding good prospects for future experimental validation and for drug repurposing towards QS inhibition.