Should We Wait to Brush Our Teeth? A Scoping Review Regarding Dental Caries and Erosive Tooth Wear.

BACKGROUND: Tooth brushing is a universal recommendation. However, the recommendations related to the time of its execution are conflicting, especially when dealing with patients at risk of erosive tooth wear (ETW) or dental caries. SUMMARY: Our objective was to summarize the evidence on the timing of brushing with fluoridated toothpaste in relation to ETW and cariogenic dietary challenges. We conducted a scoping review following the PRISMA-ScR checklist, using three databases searching for in vivo, in situ, or in vitro studies involving human teeth exposed to either a cariogenic or an erosive challenge. Only models including human saliva and fluoride were assessed. Data selection, extraction, and risk of bias analysis were done in duplicate and independently. From 1,545 identified studies, 17 (16 related to ETW and 1 to dental caries) were included. Most evidence (n = 10) supported that brushing with a fluoride-containing product does not increase ETW, independent of the moment of brushing. Delaying tooth brushing up to 1 h (n = 4) or individualized recommendations based on the patient's problem (n = 2) were less frequent. Only one study reported that brushing pre- or post-meal does not affect Streptococcus mutans counts. Most data were in situ (n = 13), and the overall study quality was judged as sufficient/low risk of bias. KEY MESSAGES: Although the available evidence lacked robust clinical studies, tooth brushing using fluoridated products immediately after an erosive challenge does not increase the risk of ETW and can be recommended, which is in line with recommendations for dental caries prevention. Furthermore, we suggest updating the international guidelines to promote individualized recommendations based on risk factors to prevent either ETW or dental caries.

Oral administration of a recombinant modified RBD antigen of SARS-CoV-2 as a possible immunostimulant for the care of COVID-19.

BACKGROUND: Developing effective vaccines against SARS-CoV-2 that consider manufacturing limitations, equitable access, and acceptance is necessary for developing platforms to produce antigens that can be efficiently presented for generating neutralizing antibodies and as a model for new vaccines. RESULTS: This work presents the development of an applicable technology through the oral administration of the SARS-CoV-2 RBD antigen fused with a peptide to improve its antigenic presentation. We focused on the development and production of the recombinant receptor binding domain (RBD) produced in E. coli modified with the addition of amino acids extension designed to improve antigen presentation. The production was carried out in shake flask and bioreactor cultures, obtaining around 200 mg/L of the antigen. The peptide-fused RBD and peptide-free RBD proteins were characterized and compared using SDS-PAGE gel, high-performance chromatography, and circular dichroism. The peptide-fused RBD was formulated in an oil-in-water emulsion for oral mice immunization. The peptide-fused RBD, compared to RBD, induced robust IgG production in mice, capable of recognizing the recombinant RBD in Enzyme-linked immunosorbent assays. In addition, the peptide-fused RBD generated neutralizing antibodies in the sera of the dosed mice. The formulation showed no reactive episodes and no changes in temperature or vomiting. CONCLUSIONS: Our study demonstrated the effectiveness of the designed peptide added to the RBD to improve antigen immunostimulation by oral administration.

Leukocyte- and Platelet-Rich Fibrin (L-PRF) Obtained from Smokers and Nonsmokers Shows a Similar Uniaxial Tensile Response In Vitro.

We evaluated and compared the biomechanical properties of Leukocyte-and Platelet Rich Fibrin L-PRF clots and membranes derived from smoker and nonsmoker donors. Twenty venous-blood donors (aged 18 to 50 years) were included after signing informed consent forms. L-PRF clots were analyzed and then compressed to obtain L-PRF membranes. L-PRF clot and membrane samples were tested in quasi-static uniaxial tension and the stress-stretch response was registered and characterized. Furthermore, scanning electron microscope representative images were taken to see the fibrin structure from both groups. The analysis of stress-stretch curves allowed us to evaluate the statistical significance in differences between smoker and nonsmoker groups. L-PRF membranes showed a stiffer response and higher tensile strength when compared to L-PRF clots. However, no statistically significant differences were found between samples from smokers and nonsmokers. With the limitations of our in vitro study, we can suggest that the tensile properties of L-PRF clots and membranes from the blood of smokers and nonsmokers are similar. More studies are necessary to fully characterize the effect of smoking on the biomechanical behavior of this platelet concentrate, to further encourage its use as an alternative to promote wound healing in smokers.

Allicin, an Emerging Treatment for Pulmonary Arterial Hypertension: An Experimental Study.

We assessed whether allicin, through its antihypertensive and antioxidant effects, relieves vascular remodeling, endothelial function, and oxidative stress (OS), thereby improving experimental pulmonary arterial hypertension (PAH). Allicin (16 mg/kg) was administered to rats with PAH (monocrotaline 60 mg/kg). Allicin encouraged body weight gain and survival rate, and medial wall thickness and the right ventricle (RV) hypertrophy were prevented. Also, angiotensin II concentrations in the lung (0.37 ± 0.01 vs. 0.47 ± 0.06 pmoles/mL, allicin and control, respectively) and plasma (0.57 ± 0.05 vs. 0.75 ± 0.064, allicin and control respectively) and the expressions of angiotensin-converting enzyme II and angiotensin II type 1 receptor in lung tissue were maintained at normal control levels with allicin. In PAH rats treated with allicin, nitric oxide (NO) (31.72 ± 1.22 and 51.4 ± 3.45 pmoles/mL), tetrahydrobiopterin (8.43 ± 0.33 and 10.14 ± 0.70 pmoles/mL), cyclic guanosine monophosphate (5.54 ± 0.42 and 5.64 ± 0.73 pmoles/mL), and Ang-(1-7) (0.88 ± 0.23 and 0.83 ± 0.056 pmoles/mL) concentrations increased in lung tissue and plasma, respectively. In contrast, dihydrobiopterin increase was prevented in both lung tissue and plasma (5.75 ± 0.3 and 5.64 ± 0.73 pmoles/mL); meanwhile, phosphodiesterase-5 was maintained at normal levels in lung tissue. OS in PAH was prevented with allicin through the increased expression of Nrf2 in the lung. Allicin prevented the lung response to hypoxia, preventing the overexpression of HIF-1α and VEGF. Allicin attenuated the vascular remodeling and RV hypertrophy in PAH through its effects on NO-dependent vasodilation, modulation of RAS, and amelioration of OS. Also, these effects could be associated with the modulation of HIF-1α and improved lung oxygenation. The global effects of allicin contribute to preventing endothelial dysfunction, remodeling of the pulmonary arteries, and RV hypertrophy, preventing heart failure, thus favoring survival. Although human studies are needed, the data suggest that, alone or in combination therapy, allicin may be an alternative in treating PAH if we consider that, similarly to current treatments, it improves lung vasodilation and increase survival. Allicin may be considered an option when there is a lack of efficacy, and where drug intolerance is observed, to enhance the efficacy of drugs, or when more than one pathogenic mechanism must be addressed.

Saliva Decreases Sucrose-Induced Cariogenicity in an Experimental Biological Caries Model.

OBJECTIVE: Whether a minimum quantity of saliva inhibit the caries process remains uncertain. This study aimed to investigate the impact of saliva dilutions on an in vitro caries model using Streptococcus mutans (S. mutans) biofilms. METHODS: S. mutans biofilms were cultivated on enamel and root dentin slabs, in culture media containing different proportions of saliva (v/v): 0%, 5%, 10%, 25%, 50%, 75%, and 100% saliva, and exposed to a 10% sucrose solution (5 min, 3x/day), with appropriate controls. After 5 (enamel) and 4 (dentin) days, demineralization, biomass, viable bacteria, and polysaccharide formation were analyzed. The acidogenicity of the spent media was monitored overtime. Each assay was performed in triplicate across two independent experiments (n = 6). RESULTS: In both enamel and dentin, an inverse relationship was observed between acidogenicity, demineralization, and the proportion of saliva. Even small quantities of saliva incorporated into the media led to a noticeable reduction in enamel and dentin demineralization. Saliva presence resulted in significant reductions in biomass, viable S. mutans cells, and polysaccharides, with the effects being concentration-dependent for both tissues. CONCLUSIONS: High quantities of saliva can almost completely inhibit sucrose-induced cariogenicity, while even small amounts exhibit a dose-dependent caries-protective effect.

SAMHD1 impairs type I interferon induction through the MAVS, IKKε, and IRF7 signaling axis during viral infection.

Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) restricts human immunodeficiency virus type 1 (HIV-1) infection by reducing the intracellular dNTP pool. We have shown that SAMHD1 suppresses nuclear factor kappa-B activation and type I interferon (IFN-I) induction by viral infection and inflammatory stimuli. However, the mechanism by which SAMHD1 inhibits IFN-I remains unclear. Here, we show that SAMHD1 inhibits IFN-I activation induced by the mitochondrial antiviral-signaling protein (MAVS). SAMHD1 interacted with MAVS and suppressed MAVS aggregation in response to Sendai virus infection in human monocytic THP-1 cells. This resulted in increased phosphorylation of TANK binding kinase 1 (TBK1), inhibitor of nuclear factor kappa-B kinase epsilon (IKKε), and IFN regulatory factor 3 (IRF3). SAMHD1 suppressed IFN-I activation induced by IKKε and prevented IRF7 binding to the kinase domain of IKKε. We found that SAMHD1 interaction with the inhibitory domain (ID) of IRF7 (IRF7-ID) was necessary and sufficient for SAMHD1 suppression of IRF7-mediated IFN-I activation in HEK293T cells. Computational docking and molecular dynamics simulations revealed possible binding sites between IRF7-ID and full-length SAMHD1. Individual substitution of F411, E416, or V460 in IRF7-ID significantly reduced IRF7 transactivation activity and SAMHD1 binding. Furthermore, we investigated the role of SAMHD1 inhibition of IRF7-mediated IFN-I induction during HIV-1 infection. We found that THP-1 cells lacking IRF7 expression had reduced HIV-1 infection and viral transcription compared to control cells, indicating a positive role of IRF7 in HIV-1 infection. Our findings suggest that SAMHD1 suppresses IFN-I induction through the MAVS, IKKε, and IRF7 signaling axis.

Effect of Casein Phosphopeptide-Amorphous Calcium Phosphate Added to Milk, Chewing Gum, and Candy on Dental Caries: A Systematic Review.

Casein is one of the most studied proteins with activity against dental caries. In particular, casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) has shown promising remineralizing properties. In vivo evidence on the anticaries potential of CPP-ACP added to foodstuffs is elusive, nonetheless. Hence, this systematic review aimed at determining whether the use of CPP-ACP added to foodstuffs has a remineralizing or inhibitory action on dental demineralization either in vivo or in situ. The review protocol followed the PRISMA-P criteria and was registered in PROSPERO. PubMed, Scopus, and Web of Science databases were searched using predefined criteria, based on the PICO question: Is there an effect on dental caries upon adding CPP-ACP to milk, chewing gums, or candies? No year or language limits were applied. Article selection and data extraction were carried out independently by 2 investigators. Two hundred ten titles were examined, 23 were selected for full-text review, and 16 studies were included (2 in vivo and 14 in situ). CPP-ACP was added to candy in 2 studies, to milk in 2 studies, and to chewing gum in 12 studies. The main outcomes included enamel remineralization and activity against dental biofilm. The overall quality of the evidence was classified as moderate. The available evidence suggests that CPP-ACP added to milk, chewing gum, or candy has a potential remineralizing activity on tooth enamel, with some additional antibacterial activity on the dental biofilm. Further clinical studies are needed to verify if this effect is clinically significant in reducing the caries lesion incidence or to revert the demineralizing process.

The host antiviral protein SAMHD1 suppresses NF-κB activation by interacting with the IKK complex during inflammatory responses and viral infection.

Sterile alpha motif and histidine-aspartate (HD) domain-containing protein 1 (SAMHD1) inhibits HIV-1 replication in nondividing cells by reducing the intracellular dNTP pool. SAMHD1 also suppresses NF-κB activation induced by inflammatory stimuli and viral infections. Specifically, SAMHD1-mediated reduction of NF-κB inhibitory protein (IκBα) phosphorylation is important for the suppression of NF-κB activation. However, while the inhibitors of NF-κB kinase subunit alpha and beta (IKKα and IKKß) regulate IκBα phosphorylation, the mechanism by which SAMHD1 regulates phosphorylation of IκBα remains unclear. Here, we report that SAMHD1 suppresses phosphorylation of IKKα/ß/γ via interaction with IKKα and IKKß, thus inhibiting subsequent phosphorylation of IκBα in monocytic THP-1 cells and differentiated nondividing THP-1 cells. We show that knockout of SAMHD1 enhanced phosphorylation of IKKα, IKKß, and IKKγ in THP-1 cells treated with the NF-κB activator lipopolysaccharide or infected with Sendai virus and SAMHD1 reconstitution inhibited phosphorylation of IKKα/ß/γ in Sendai virus-infected THP-1 cells. We demonstrate that endogenous SAMHD1 interacted with IKKα and IKKß in THP-1 cells and recombinant SAMHD1 bound to purified IKKα or IKKß directly in vitro. Mapping of these protein interactions showed that the HD domain of SAMHD1 interacts with both IKKα and IKKß and that the kinase domain of IKKα and the ubiquitin-like domain of IKKß are required for their interactions with SAMHD1, respectively. Moreover, we found that SAMHD1 disrupts the interaction between upstream kinase TAK1 and IKKα or IKKß. Our findings identify a new regulatory mechanism by which SAMHD1 inhibits phosphorylation of IκBα and NF-κB activation.

Epitranscriptomic N6-Methyladenosine Profile of SARS-CoV-2-Infected Human Lung Epithelial Cells.

N6-methyladenosine (m6A) is a dynamic posttranscriptional RNA modification that plays an important role in determining transcript fate. The functional consequence of m6A deposition is dictated by a group of host proteins that specifically recognize and bind the m6A modification, leading to changes in RNA stability, transport, splicing, or translation. The cellular m6A methylome undergoes changes during certain pathogenic conditions such as viral infections. However, how m6A modification of host cell transcripts and noncoding RNAs change during severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection has not been reported. Here, we define the epitranscriptomic m6A profile of SARS-CoV-2-infected human lung epithelial cells compared to uninfected controls. We identified mRNA and long and small noncoding RNA species that are differentially m6A modified in response to SARS-CoV-2 infection. The most significantly differentially methylated transcript was the precursor of microRNA-4486 (miRNA-4486), which showed significant increases in abundance and percentage of methylated transcripts in infected cells. Pathway analyses revealed that differentially methylated transcripts were significantly associated with several cancer-related pathways, protein processing in the endoplasmic reticulum, cell death, and proliferation. Upstream regulators predicted to be associated with the proteins encoded by differentially methylated mRNAs include several proteins involved in the type-I interferon response, inflammation, and cytokine signaling. IMPORTANCE Posttranscriptional modification of viral and cellular RNA by N6-methyladenosine (m6A) plays an important role in regulating the replication of many viruses and the cellular immune response to infection. We therefore sought to define the epitranscriptomic m6A profile of human lung epithelial cells infected with SARS-CoV-2. Our analyses demonstrate the differential methylation of both coding and noncoding cellular RNAs in SARS-CoV-2-infected cells compared to uninfected controls. Pathway analyses revealed that several of these RNAs may be involved in the cellular response to infection, such as type-I interferon. Our study implicates m6A modification of infected-cell RNA as a mechanism of posttranscriptional gene regulation during SARS-CoV-2 infection.

Smoking habits do not affect biological responses induced by leucocyte and platelet-rich fibrin in periodontal ligament cells.

BACKGROUND AND OBJECTIVE: Leucocyte- and platelet-rich fibrin has been developed to stimulate wound healing response. However, it is currently unknown whether smoking affects the biological responses elicited by leucocyte- and platelet-rich fibrin on periodontal ligament-derived mesenchymal stromal cells. This study analyzes the kinetics of biomolecule release from leucocyte- and platelet-rich fibrin derived from smokers and nonsmokers and their effect on periodontal ligament cell proliferation and migration as essential biological activities during wound healing. METHODS: Biomolecules present in leucocyte- and platelet-rich fibrin exudates and conditioned media collected from smokers and nonsmokers were analyzed by Luminex arrays. Periodontal ligament-derived mesenchymal stromal cell obtained from one nonsmoker were treated with leucocyte- and platelet-rich fibrin exudates or leucocyte- and platelet-rich fibrin conditioned media derived from both smokers and nonsmokers. The parameters evaluated included cell proliferation, determined by Ki67 immunostaining and migration assessed using transwell assays. Also, cells were treated with nicotine in the presence of fetal bovine serum 10% or leucocyte- and platelet-rich fibrin conditioned media. RESULTS: A similar biomolecular profile was detected in leucocyte- and platelet-rich fibrin exudates and leucocyte- and platelet-rich fibrin conditioned media from smokers and nonsmokers, stimulating (periodontal ligament-derived mesenchymal stromal cell) proliferation, and migration to a comparable degree. Nicotine reduced cell proliferation and migration of periodontal cells; however, this effect was recovered in the presence of leucocyte- and platelet-rich fibrin conditioned media. CONCLUSION: Leucocyte- and platelet-rich fibrin derived from smokers could be an autologous source of biomolecules to stimulate cell biological activities involved in wound healing in smokers who have difficulties in ceasing this habit. Clinical trials are required to evaluate the impact of leucocyte- and platelet-rich fibrin on healing responses in smokers.

Understanding dental caries as a non-communicable and behavioral disease: Management implications.

New paradigms in caries conceptualization have emerged during the last decades, leading to intense debate and discussion on how to approach the disease, both from a preventive and a therapeutic perspective. Among many new ideas, research discoveries and technologies, one major concept can be highlighted that created a deep frontier between the old and the new paradigm in caries conceptualization; the non-communicable nature of the disease, firmly associated with behaviors and lifestyles. This article synthetizes the conceptual construction of dental caries as a non-communicable disease (NCD) based on the current evidence and discusses the appropriate management of the disease in this context. Dental caries has shifted from being considered transmissible and infectious to an ecological and non-communicable disease. Environmental factors such as frequent sugars intake, disrupt the symbiosis of the dental biofilm leading to a dysbiosis, which favors caries lesion initiation and progression. As an NCD, dental caries shares characteristics with other NCDs such as cardiovascular and chronic respiratory diseases, cancer and diabetes, including long duration and slow progression, not being transmissible from person-to-person, being strongly related to modifiable behavioral risk factors, and affecting preferentially disadvantaged populations with a strong inequality gradient. Given the high prevalence of dental caries, and its consequences on people's health and quality of life, a recognizable conceptual view of caries as a NCD is required to target an effective management. Current understanding of dental caries supports prevention through acting on the modifiable risk factors (behaviors) and involves management based on an interdisciplinary approach. Communicating these modern concepts among researchers, clinicians and policymakers is needed to decrease the global high burden of the disease.

Fluoride concentration in teas derived from Camellia Sinensis produced in Argentina.

To evaluate the fluoride concentration and pH of tea derived from Camellia sinensis produced and commercialized in Argentina. Forty-eight varieties of tea (black (n = 16), green (n = 21), red (n = 7), and white (n = 4)) commercialized in the form of leaves or tea bags were acquired. One bag or 2.0 ± 0.05 g of each product was infused for 5 min in 200 mL of distilled boiled water. The F- concentration was determined using an ion-selective electrode and pH was measured using a pH meter. The found fluoride concentrations ranged from 0.1 to 9.7 µg/mL and the pH ranged from 2.7 to 5.1. A higher fluoride concentration was observed in the leaves group (2.75 ± 2.65 µg/mL) compared to tea bags (1.10 ± 0.82 µg/mL) (p < 0.05). Regarding the type of tea, green and black tea were richer in F- than red and white tea. Fluoride and pH appeared not to be correlated (Pearson test). All the studied tea samples presented fluoride concentrations greater than the threshold recommended for drinking water. The pH proved to be low, which could be a risk for erosive tooth wear.

Epitranscriptomic N6-methyladenosine profile of SARS-CoV-2-infected human lung epithelial cells

N6-methyladenosine (m6A) is a dynamic post-transcriptional RNA modification that plays an important role in determining transcript fate. Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has caused the global pandemic of coronavirus disease 2019 (COVID-19) and the virus has been extensively studied. However, how m6A modification of host cell RNAs change during SARS-CoV-2 infection has not been reported. Here we define the epitranscriptomic m6A profile of SARS-CoV-2-infected human lung epithelial cells compared to uninfected controls. Biological pathway analyses revealed that differentially methylated transcripts were significantly associated with cancer-related pathways, protein processing in the endoplasmic reticulum, cell death and proliferation. Upstream regulators predicted to be associated with the proteins encoded by differentially methylated mRNAs include proteins involved in the type I interferon response, inflammation, and cytokine signaling. These data suggest that m6A modification of cellular RNA is an important mechanism of regulating host gene expression during SARS-CoV-2 infection of lung epithelial cells.

Effect of pH and titratable acidity on enamel and dentine erosion.

OBJECTIVES: The relative effect of pH and titratable acidity on tooth erosion remains unclear. We determined the effect of both properties on in vivo salivary pH recovery and on enamel and dentine early erosion in situ. METHODS: Solutions simulating acidic beverages with different pHs (2.5 or 3.5) and titratable acidities (0, 25, or 100 mM citric acid) were tested. In an in vivo study (n = 20 participants), the salivary pH was determined before, during, and up to 2 min after exposure to the tested solutions. In situ, 12 participants exposed enamel and root dentine slabs to the tested solutions simulating a beverage consumption; early erosion was assessed by percentage of surface hardness loss (%SHL). Groups were compared by ANOVA (p < 0.05). RESULTS: Saliva pH was lower after exposure to solutions at pH 2.5, irrespective of titratable acidity; pH recovery took longer for solutions with higher titratable acidities, irrespective of their pHs. In situ, the highest %SHL was observed for the solution with lower pH and higher titratable acidities. The addition of citric acid increased the %SHL by 2.5-3 times in enamel, and at least 5 times in dentine. CONCLUSIONS: Both pH and titratable acidity may play a role on the erosive potential of acidic beverages. CLINICAL RELEVANCE: Acidic beverages with lower pHs promote erosion by an initial acid etching of the surface; those with a higher titratable acidity slow down the salivary pH recovery. Both properties contribute to the overall erosive potential.

Unsweetened and sucrose-sweetened black and green tea modifies the architecture of in vitro oral biofilms.

OBJECTIVE: It is unclear whether tea infusions with or without sucrose supplementation alter oral biofilm development, so we evaluated the effect of unsweetened and sucrose-sweetened black and green tea infusions on in vitro saliva-derived biofilms. DESIGN: Biofilms were developed from human saliva for 20 h in cell-free 25% human saliva within static glass-bottom microplates. During biofilm development, biofilms were treated with either (i) unsweetened black tea, (ii) unsweetened green tea, (iii) 10% sucrose-sweetened black tea, (iv) 10% sucrose-sweetened green tea (v) deionized water (negative control), or (vi) 10% sucrose (positive control). Biofilms were incubated at 37 °C in 5% CO2. After 20 h of development, biofilms were imaged using a CLSM, and biofilm architecture and viability were evaluated. RESULTS: All the tea infusions reduced biofilm biomass and altered some other biofilm architectural outcomes (e.g., biofilm surface area) compared to the control groups. Statistically significant differences in biofilm biomass, number of objects, surface area, and convex-hull porosity were observed between biofilms treated with green and black tea. The addition of sugar to tea did not significantly modify the ability of tea to alter biofilm architecture. Only the treatment of biofilms with unsweetened black tea significantly reduced bacterial viability. CONCLUSIONS: While both teas reduced biofilm biomass and altered biofilm architecture, black tea had an enhanced effect that may relate to this tea's observed antimicrobial activity. The addition of sucrose to tea infusions did not appear to reduce the impact of either tea in modifying oral biofilm architecture.

Hegemony of economic values in conducting clinical trials with a placebo-control group to investigate the treatment of periodontitis in lower-middle-income countries.

This article analyzes the bioethical implications of using a control/placebo group when conducting clinical trials (CTs) investigating the treatment of periodontitis. For this, the deductive method was used, proposing the interrelation of values, and a scoping systematic review was carried out. A total of 53% of the CTs reviewed were performed in low- and middle-income (LMI) countries, and 92% used a control/placebo group as a comparison group. Although there is a gold standard for the adjunctive treatment of periodontitis, the research ethics committees of most of the analyzed studies approved the use of control/placebo groups for the performance of CTs that did not explore new therapeutic alternatives. In some cases, the CT protocols were not approved by ethics committees, nor was informed consent used. In the LMI countries, a shorter period of recruitment was observed for patients who attended universities and public hospitals. Likewise, most of the CTs reviewed had public funding, a significant amount of which came from the pharmaceutical industry. Only one CT reported the low economic and educational level of its participants. Furthermore, none of the authors of the reviewed CTs declared conflicts of interest. Although the axiology of techno-science always takes into account at least the epistemic, technical and economic value systems, the hegemony of the economic values imposed by the pharmaceutical industry is evident in the performance of CTs investigating the treatment of periodontitis in LMI countries.

¿Cómo Intervenir el Proceso de Caries en Adultos? Adaptación del Consenso de ORCA/EFCD/DGZ / How to Intervene the Caries Process in Adults? Adaptation of the ORCA/EFCD/DGZ Consensus

RESUMEN: El manejo terapéutico de lesiones de caries primarias y secundarias concentra gran parte del quehacer de los dentistas en el mundo. Recientes cambios en la concepción de la enfermedad de caries llevaron a un panel de expertos de la Organización Europea para la Investigación en Caries (ORCA), la Federación Europea de Odontología Conservadora (EFCD) y la Federación Alemana de Odontología Conservadora (DGZ) a analizar la evidencia y consensuar recomendaciones sobre manejo de caries en adultos. Mediante una reunión en Berlín, Alemania en 2019 y con metodología e-Delphi, los expertos analizaron la evidencia y propusieron recomendaciones clínicas. El propósito de este artículo es presentar una adaptación idiomática de las principales recomendaciones, que incluyen terapias no invasivas (higiene, uso de fluoruros y control de dieta), terapias microinvasiva (sellantes e infiltrantes), terapias necesariamente invasivas y la reparación de restauraciones. Todas las recomendaciones se basan en un enfoque mínimamente invasivo, con un adecuado manejo restaurador. Los dentistas de países hispanoparlantes podrán encontrar recomendaciones basadas en evidencia, provenientes de un consenso de expertos a nivel global, que orienten sus decisiones clínicas, apoyándose en los principios de la odontología de mínima intervención.

ABSTRACT: Therapeutic management of primary and secondary caries lesions concentrates much of the work of dentists throughout the world. Recent changes in caries disease conception and therapeutic management led a panel of experts from the European Organisation for Caries Research (ORCA), the European Federation for Conservative Dentistry (EFCD) and the German Federation for Conservative Dentistry (DGZ) to analyze the evidence and reach consensus on recommendations for caries management in adults. Through a meeting held in Berlin, Germany in 2019 and using an e-Delphi methodology, the experts analyzed the evidence and proposed clinical recommendations. The purpose of this article is to present an idiomatic adaptation to Spanish of the main recommendations, which include non-invasive therapies (hygiene, use of fluoride and diet control), microinvasive therapies (sealants and infiltrants), invasive therapies and repair of restorations. All recommendations are based on a minimally invasive dentistry approach, with a technically adequate restorative management. Spanish-speaking dentists may use these consensus recommendations to guide their clinical decisions, based on the most recent evidence and experts opinions, under the principles of minimal intervention dentistry.

N6-methyladenosine modification of HIV-1 RNA suppresses type-I interferon induction in differentiated monocytic cells and primary macrophages.

N6-methyladenosine (m6A) is a prevalent RNA modification that plays a key role in regulating eukaryotic cellular mRNA functions. RNA m6A modification is regulated by two groups of cellular proteins, writers and erasers that add or remove m6A, respectively. HIV-1 RNA contains m6A modifications that modulate viral infection and gene expression in CD4+ T cells. However, it remains unclear whether m6A modifications of HIV-1 RNA modulate innate immune responses in myeloid cells that are important for antiviral immunity. Here we show that m6A modification of HIV-1 RNA suppresses the expression of antiviral cytokine type-I interferon (IFN-I) in differentiated human monocytic cells and primary monocyte-derived macrophages. Transfection of differentiated monocytic U937 cells with HIV-1 RNA fragments containing a single m6A-modification significantly reduced IFN-I mRNA expression relative to their unmodified RNA counterparts. We generated HIV-1 with altered m6A levels of RNA by manipulating the expression of the m6A erasers (FTO and ALKBH5) or pharmacological inhibition of m6A addition in virus-producing cells, or by treating HIV-1 RNA with recombinant FTO in vitro. HIV-1 RNA transfection or viral infection of differentiated U937 cells and primary macrophages demonstrated that HIV-1 RNA with decreased m6A levels enhanced IFN-I expression, whereas HIV-1 RNA with increased m6A modifications had opposite effects. Our mechanistic studies indicated that m6A of HIV-1 RNA escaped retinoic acid-induced gene I (RIG-I)-mediated RNA sensing and activation of the transcription factors IRF3 and IRF7 that drive IFN-I gene expression. Together, these findings suggest that m6A modifications of HIV-1 RNA evade innate immune sensing in myeloid cells.

TRAF6 and TAK1 Contribute to SAMHD1-Mediated Negative Regulation of NF-κB Signaling.

Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) restricts HIV-1 replication by limiting the intracellular deoxynucleoside triphosphate (dNTP) pool. SAMHD1 also suppresses the activation of NF-κB in response to viral infections and inflammatory stimuli. However, the mechanisms by which SAMHD1 negatively regulates this pathway remain unclear. Here, we show that SAMHD1-mediated suppression of NF-κB activation is modulated by two key mediators of NF-κB signaling, tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and transforming growth factor ß-activated kinase 1 (TAK1). We compared NF-κB activation stimulated by interleukin (IL)-1ß in monocytic THP-1 control and SAMHD1 knockout (KO) cells with and without partial TRAF6 knockdown (KD), or in cells treated with TAK1 inhibitors. Relative to control cells, IL-1ß-treated SAMHD1 KO cells showed increased phosphorylation of the inhibitor of NF-κB (IκBα), an indication of pathway activation, and elevated levels of TNF-α mRNA. Moreover, SAMHD1 KO combined with TRAF6 KD or pharmacological TAK1 inhibition reduced IκBα phosphorylation and TNF-α mRNA to the level of control cells. SAMHD1 KO cells infected with single-cycle HIV-1 showed elevated infection and TNF-α mRNA levels compared to control cells, and the effects were significantly reduced by TRAF6 KD or TAK1 inhibition. We further demonstrated that overexpressed SAMHD1 inhibited TRAF6-stimulated NF-κB reporter activity in HEK293T cells in a dose-dependent manner. SAMHD1 contains a nuclear localization signal (NLS), but an NLS-defective SAMHD1 exhibited a suppressive effect similar to the wild-type protein. Our data suggest that the TRAF6-TAK1 axis contributes to SAMHD1-mediated suppression of NF-κB activation and HIV-1 infection.IMPORTANCE Cells respond to pathogen infection by activating a complex innate immune signaling pathway, which culminates in the activation of transcription factors and secretion of a family of functionally and genetically related cytokines. However, excessive immune activation may cause tissue damage and detrimental effects on the host. Therefore, in order to maintain host homeostasis, the innate immune response is tightly regulated during viral infection. We have reported SAMHD1 as a novel negative regulator of the innate immune response. Here, we provide new insights into SAMHD1-mediated negative regulation of the NF-κB pathway at the TRAF6-TAK1 checkpoint. We show that SAMHD1 inhibits TAK1 activation and TRAF6 signaling in response to proinflammatory stimuli. Interestingly, TRAF6 knockdown in SAMHD1-deficient cells significantly inhibited HIV-1 infection and activation of NF-κB induced by virus infection. Our research reveals a new negative regulatory mechanism by which SAMHD1 participates in the maintenance of cellular homeostasis during HIV-1 infection and inflammation.

COVID-19 pandemic accelerated virtual transformation in dental education: a multicenter review of remote teaching and teledentistry / Transformação virtual acelerada pela pandemia de COVID-19 na educação odontológica: uma revisão multicêntrica do ensino à distância e da teleodontologia

ABSTRACT Although prior to the pandemic there was some resistance to the virtualization of dental education, the COVID-19 pandemic is providing us a unique opportunity to overcome several barriers that previously blocked the adoption of remote teaching and teledentistry. Thanks to the extended availability of telecommunications, digital technologies, and platforms, remote education and teledentistry appear to be the preferred choice to maintain dental education and patient care active under this pandemic, without contamination risks. In this paper, we review valid remote education strategies and possible alternatives useful in virtual transformation in dental education. Furthermore, the role of teledentistry and its advantages and challenges are also revised. Under the current pandemic context, as dental educators, we are called to be creative and flexible. Every dental school should adapt and use remote education as much as possible until clinical attention can be readopted. The evidence presented in this review supports our position that under this pandemic, remote education and telemedicine/teledentistry may be "the virtual convenient solution", to adapt and improve the hitherto classic way of teaching dentistry through tele-education.

RESUMO Embora antes da pandemia houvesse alguma resistência à virtualização da educação odontológica, a pandemia COVID-19 está nos fornecendo uma oportunidade única de superar várias barreiras que anteriormente bloqueavam a adoção do ensino à distância e teledontologia. Graças à ampla disponibilidade de telecomunicações, tecnologias digitais e plataformas, a educação à distância e a teledontologia parecem ser a escolha preferida para manter a educação odontológica e o atendimento ativo aos pacientes durante a pandemia, sem riscos de contaminação. Neste artigo, revisamos estratégias válidas de educação a distância e possíveis alternativas úteis na transformação virtual na educação odontológica. Além disso, o papel do teleodontologia e suas vantagens, assim como também os desafios. No atual contexto pandêmico, como educadores odontológicos, somos chamados a ser criativos e flexíveis. Cada escola de odontologia deve se adaptar e usar a educação à distância, tanto quanto possível, até que a atenção clínica possa ser readotada. As evidências apresentadas nesta revisão corroboram nossa posição de que, sob esta pandemia, a educação a distância e a telemedicina / teleodontologia podem ser "a solução virtual conveniente", para adaptar e aprimorar a forma até então clássica de ensino de odontologia, agora por meio da teleducação.