Modulating the sEH/EETs Axis Restrains Specialized Proresolving Mediator Impairment and Regulates T Cell Imbalance in Experimental Periodontitis.

Epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids are short-acting lipids involved in resolution of inflammation. Their short half-life, due to its metabolism by soluble epoxide hydrolase (sEH), limits their effects. Specialized proresolving mediators (SPMs) are endogenous regulatory lipids insufficiently synthesized in uncontrolled and chronic inflammation. Using an experimental periodontitis model, we pharmacologically inhibited sEH, examining its impact on T cell activation and systemic SPM production. In humans, we analyzed sEH in the gingival tissue of periodontitis patients. Mice were treated with sEH inhibitor (sEHi) and/or EETs before ligature placement and treated for 14 d. Bone parameters were assessed by microcomputed tomography and methylene blue staining. Blood plasma metabololipidomics were carried out to quantify SPM levels. We also determined T cell activation by reverse transcription-quantitative PCR and flow cytometry in cervical lymph nodes. Human gingival samples were collected to analyze sEH using ELISA and electrophoresis. Data reveal that pharmacological sEHi abrogated bone resorption and preserved bone architecture. Metabololipidomics revealed that sEHi enhances lipoxin A4, lipoxin B4, resolvin E2, and resolvin D6. An increased percentage of regulatory T cells over Th17 was noted in sEHi-treated mice. Lastly, inflamed human gingival tissues presented higher levels and expression of sEH than did healthy gingivae, being positively correlated with periodontitis severity. Our findings indicate that sEHi preserves bone architecture and stimulates SPM production, associated with regulatory actions on T cells favoring resolution of inflammation. Because sEH is enhanced in human gingivae from patients with periodontitis and connected with disease severity, inhibition may prove to be an attractive target for managing osteolytic inflammatory diseases.

Silicon attenuates nutritional disorder of phosphorus in seedlings of Eucalyptus grandis × Eucalyptus urophylla.

BACKGROUND: Nutritional disorders of phosphorus (P), due to deficiency or toxicity, reduce the development of Eucalyptus spp. seedlings. Phosphorus deficiency often results in stunted growth and reduced vigor, while phosphorus toxicity can lead to nutrient imbalances and decreased physiological function. These sensitivities highlight the need for precise management of P levels in cultivation practices. The use of the beneficial element silicon (Si) has shown promising results under nutritional stress; nevertheless, comprehensive studies on its effects on Eucalyptus spp. seedlings are still emerging. To further elucidate the role of Si under varying P conditions, an experiment was conducted with clonal seedlings of a hybrid Eucalyptus spp. (Eucalyptus grandis × Eucalyptus urophylla, A207) in a soilless cultivation system. Seedlings were propagated using the minicutting method in vermiculite-filled tubes, followed by treatment with a nutrient solution at three P concentrations: a deficient dose (0.1 mM), an adequate dose (1.0 mM) and an excessive dose (10 mM), with and without the addition of Si (2mM). This study assessed P and Si concentration, nutritional efficiency, oxidative metabolism, photosynthetic parameters, and dry matter production. RESULTS: Si supply increased phenolic compounds production and reduced electrolyte leakage in seedlings provided with 0.1 mM of P. On the other hand, Si favored quantum efficiency of photosystem II as well as chlorophyll a content in seedlings supplemented with 10 mM of P. In general, Si attenuates P nutritional disorder by reducing the oxidative stress, favoring the non-enzymatic antioxidant system and photosynthetic parameters in seedlings of Eucalyptus grandis × Eucalyptus urophylla. CONCLUSION: The results of this study indicate that Eucalyptus grandis × Eucalyptus urophylla seedlings are sensitive to P deficiency and toxicity and Si has shown a beneficial effect, attenuating P nutritional disorder by reducing the oxidative stress, favoring the non-enzymatic antioxidant system and photosynthetic parameters.

Periodontal pathogen Aggregatibacter actinomycetemcomitans JP2 correlates with colonic leukocytes decrease and gut microbiome imbalance in mice.

AIM: Evidence suggests that translocation of oral pathogens through the oral-gut axis may induce intestinal dysbiosis. This study aimed to evaluate the impact of a highly leukotoxic Aggregatibacter actinomycetemcomitans (Aa) strain on the gut microbiota, intestinal mucosal integrity and immune system in healthy mice. METHODS: Eight-week-old male C57BL6 mice were divided into control (n = 16) and JP2 groups (n = 19), which received intragastric gavage with PBS and with a suspension of Aa JP2 (HK921), respectively, twice a week for 4 weeks. Colonic lamina propria, fecal material, serum, gingival tissues, and mandibles were obtained for analyses of leukocyte populations, inflammatory mediators, mucosal integrity, alveolar bone loss, and gut microbiota. Differences between groups for these parameters were examined by non-parametric tests. RESULTS: The gut microbial richness and the number of colonic macrophages, neutrophils, and monocytes were significantly lower in Aa JP2-infected mice than in controls (p < .05). In contrast, infected animals showed higher abundance of Clostridiaceae, Lactobacillus taiwanensis, Helicobacter rodentium, higher levels of IL-6 expression in colonic tissues, and higher splenic MPO activity than controls (p < .05). No differences in tight junction expression, serum endotoxin levels, and colonic inflammatory cytokines were observed between groups. Infected animals presented also slightly more alveolar bone loss and gingival IL-6 levels than controls (p < .05). CONCLUSION: Based on this model, intragastric administration of Aa JP2 is associated with changes in the gut ecosystem of healthy hosts, characterized by less live/recruited myeloid cells, enrichment of the gut microbiota with pathobionts and decrease in commensals. Negligible levels of colonic pro-inflammatory cytokines, and no signs of mucosal barrier disruption were related to these changes.

Influence of surgeon experience on implant placement in guided surgeries: A systematic review and meta-analysis of randomized clinical trials.

STATEMENT OF PROBLEM: Guided surgical techniques in implant dentistry use virtual planning to accurately position implants. Understanding the effect of a surgeon's experience on guided surgery is essential to ensure successful outcomes. PURPOSE: The purpose of this systematic review and meta-analysis of randomized clinical trials was to evaluate the influence of a surgeon's experience on the accuracy of implant positioning in guided surgery for completely or partially edentulous patients. MATERIAL AND METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, searches were conducted in the PubMed, Scopus, Web of Science, EMBASE, Cochrane Library, SciELO, and nonpeer-reviewed literature databases. Studies that met the population, intervention, control, and outcome (PICO) strategy were included: a completely or partially edentulous maxilla or mandible, guided surgery performed by experienced and inexperienced surgeons, and assessing implant positioning accuracy. A random-effects meta-analysis with a 95% confidence interval was conducted using Stata 15.1. The risk of bias was assessed with the Cochrane risk-of-bias tool for randomized trials (RoB2), and evidence certainty was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool. The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42022302288). RESULTS: Three articles from 2017 to 2020 encompassing 43 participants (22 men and 21 women) with a mean age of 61.2 years and a total of 150 implants were included. No significant difference was found between experienced and inexperienced surgeons in terms of angular, cervical, or apical deviations of the implants (95% confidence interval, P<.05). The difference between surgeons regarding positioning accuracy was less than 0.01 degrees for angular deviation, 0.35 mm for apical deviation, and 0.16 mm for cervical deviation. Low heterogeneity was observed for angular deviations (Q P=.021, I2=34%, and t2<.001) and cervical deviations (Q P=.18, I2=45%, and t2=.064). High heterogeneity was observed for apical deviations (Q P<.001, I2=87% and t2=.522). The overall bias risk was moderate, with the evidence certainty ranging from low to moderate. CONCLUSIONS: In guided surgery, the surgeon's experience did not significantly impact the occurrence of deviations in implant positioning.

Three-dimensional replica of the temporal bone in the teaching of human anatomy.

PURPOSE: The current study proposes the comparison of the visualization and identification of anatomical details between natural human temporal bone, its respective copy from three-dimensional printing, and the virtual model obtained from CBCT. METHODS: The sample consisted of undergraduate students in Dentistry (Group UE, n = 22), Postgraduate students in Radiology and Imaging (Group P-RI, n = 20), and Postgraduate students in Forensic Odontology (Group P-FO, n = 24). All participants attended a theoretical class on specialized anatomy of the temporal bone and subsequently performed the markings of 10 determined structures. RESULTS: The number of correct identifications was similar in natural bone and printed three-dimensional models in all groups (p > 0.05). The virtual model showed a significantly lower number of correct structures (p < 0.05) in the 3 groups. In general, there were significantly higher percentages of accurate answers among postgraduate students compared to undergraduate students. Most graduate students believed that the printed three-dimensional model could be used to teach anatomy in place of natural bone, while undergraduate students disagreed or were unsure (p < 0.05). Regarding the virtual tomographic image, in all groups, students disagreed or were not sure that its use would be beneficial in replacing natural bone. CONCLUSION: Three-dimensional and virtual models can be used as auxiliary tools in teaching anatomy, complementing practical learning with natural bones.

Atypical antipsychotics olanzapine and clozapine increase bone loss in female rats with experimental periodontitis.

BACKGROUND AND OBJECTIVES: Periodontitis is a highly prevalent disease in psychiatric patients, including those undergoing symptomatic treatment with second-generation antipsychotics. Some of these drugs, such as clozapine (CLO) and olanzapine (OLA), have prominent metabolic effects such as weight gain, hyperglycemia, and dyslipidemia, which are risk factors for periodontitis. In addition to the metabolic effects, there are reports of changes in salivary flow, gingival bleeding, and caries. In this context, we aimed to evaluate if the metabolic effects of OLA and CLO alter periodontal parameters in an animal model of periodontitis without the environmental and psychosocial biases inherent to human diseases. METHODS: In the first set of experiments, male and female adult Wistar rats received oral administration of CLO, OLA, or vehicle for 45 days. They were evaluated for body mass composition and weight gain, blood glucose parameters (fasting and glucose tolerance and insulin resistance tests), and lipid profile (HDL, total cholesterol, and triglycerides). In a second set of experiments, the same measurements were performed in female rats exposed to the antipsychotics for 45 days and ligature-induced periodontitis on the 30th day of treatment. Macroscopic measurements of exposed roots, microtomography in the furcation region of the first molar, and histological evaluation of the region between the first and second molars were evaluated to assess bone loss. Additionally, gingival measurements of myeloperoxidase activity and pro-inflammatory cytokine TNF-α were made. RESULTS: Only females exposed to OLA had more significant weight gain than controls. They also exhibited differences in glucose metabolism. Ligature-induced periodontitis produced intense bone retraction without changing the density of the remaining structures. The bone loss was even higher in rats with periodontitis treated with OLA or CLO and was accompanied by a local increase in TNF-α caused by CLO. These animals, however, did not exhibit the same metabolic impairments observed for animals without periodontitis. CONCLUSION: The use of clozapine and olanzapine may be a risk factor for periodontal disease, independent of systemic metabolic alterations.

Endocrine-disrupting chemicals and endocrine neoplasia: A forty-year systematic review.

INTRODUCTION: Endocrine disrupting chemicals (EDCs) are exogenous substances recognised as relevant tumourigenic chemicals. Studies show that even EDCs which were long abolished are still contributing to the increasing incidence of neoplasia. AIM: To investigate the association between human exposure to EDCs and the risk of endocrine-related tumours: breast, prostate, thyroid, uterus, testis, and ovary. METHODS: A systematic review using PubMed, Scopus, and Embase was conducted, searching for original observational studies published between 1980 and 2020, approaching EDCs exposure and endocrine tumourigenic risk in humans. We comprised neoplasia of six endocrine organs. We included all the studies on EDCs reporting tumour odds ratio, risk ratio, or hazard ratio. Study levels of confidence and risk of bias were accessed applying accredited guidelines. Human-made accidents and natural EDCs were not considered in the present study. RESULTS: Our search returned 3271 papers. After duplicate removal and screening, only 237 papers were included (corresponding to 268 records). EDCs were grouped from the most frequently (pesticides) to the least frequently studied (salts). The most tumourigenic EDC groups were phthalates (63%), heavy metals (54%), particulate matter (47%), and pesticides (46%). Pesticides group comprised the highest number of retrieved studies (n = 133). Increased neoplasia risk was found in 43-67% of the studies, with a lower value for ovary (43%) and a higher value for thyroid (67%). CONCLUSIONS: The innovative nature of our review comes from including human studies of six endocrine-related neoplasia aiming to understand the contribution of specific EDCs groups to each organ's tumourigenesis. Thyroid was the organ presenting the highest cancer risk after EDC exposure which may explain the increasing thyroid cancer incidence. However, detailed and controlled works reporting the effects of EDCs are scarce, probably justifying conflicting results. Multinational and multicentric human studies with biochemical analysis are needed to achieve stronger and concordant evidence.

Radiographic dental age estimation applying and comparing Demirjian's seven (1973) and four (1976) teeth methods.

To apply Demirjian's seven (1973, D7) and four (1976, D4) teeth methods in a sample of Brazilian children and compare their performances for age estimation. Panoramic radiographs of 1200 children (600 females and 600 males) were collected from Southeast Brazil. The children were equally distributed (n = 60 females and 60 males) between age intervals of 1 year between 6 and 15.9 (mean age = 10.9; standard deviation [SD]: 2.9) years. D7 and D4 dental age estimation methods were applied by two observers and were compared based on their error rates (error = estimated age-chronological age). Both methods overestimated the chronological age (p < 0.0001). D7 led to overestimations of 0.71 (p < 0.0001) in females and 0.83 (p < 0.0001) in males, while the overestimations with D4 were 0.14 (p = 0.0067) and 0.73 (p < 0.0001) for females and males, respectively. The mean age estimated by D7 was 11.7 (SD: 3.1) years, while for D4, it was 11.3 (SD: 3.3) years. Intra- and interobserver agreement was ≥ 0.98. D4 optimized the performance of radiographic dental age estimation compared to D7. Improvements were reflected in the total sample and separately for female and male children from Southeast Brazil.

What is the best anthropometric predictor for identifying higher risk for cardiovascular diseases in afro-descendant Brazilian women? A cross-sectional population-based study.

OBJECTIVES: Excessive adiposity is associated with cardiovascular disease (CVD). Anthropometric indices are useful in screening individuals at higher risk for these diseases. However, there are no studies that show which of these indices has the best discriminatory power among Afro-descendant Brazilian women. The objective of this study was to assess the accuracy of anthropometric indices in identifying risk factors for CVD in Afro-descendant Brazilian women and define the one most suitable for use under the operating conditions prevailing in Quilombola communities. METHODS: A household random sample of 1661 women descendants of African slaves were analyzed. The anthropometric predictors analyzed were waist circumference (WC), body mass index, waist-to-height ratio, conicity index (C-index), body shape index, and percentage of body fat (%BF; estimated by bioimpedance). The assessed risk factors for CVD were arterial hypertension, diabetes mellitus, and dyslipidemias (hypertriglyceridemia; hypercholesterolemia; low high-density lipoprotein). To identify the statistical significance between the differences in the areas under the ROC curves (AUC) obtained with the different predictors and outcomes, was used the Bonferroni test adjusted for multiple analyses by the Sidak method. RESULTS: The AUC obtained with WC was higher (p < .05) or similar (p > .05) to those obtained with the other predictors 29 times out of 30 possibilities (six predictors x five outcomes). Only the AUC obtained with C-index in identifying hypercholesterolemia was significantly higher than that with WC. CONCLUSION: Due to its accuracy and greater operational simplicity, WC was the most adequate predictor for identifying Afro-descendant women at greatest risk for CVD.

A large sample-sized study on dental development of children treated at the Central Dental Clinic (OCEx) of the Brazilian Army.

OBJECTIVES: To test and compare the performance of two radiographic methods for dental age estimation on a large sample of Brazilian boys and girls. MATERIAL AND METHODS: The sample consisted of 1.990 panoramic radiographs of Brazilian children (age: 3-15.9 years) equally balanced based on sex. The sample was distributed into ten age categories, each with up to 200 children. Age estimation was performed with Willems' (2001) and Demirjian's (1973) methods. Estimated (EA) and chronological (CA) ages were compared. The performances of the methods were quantified based on sex and age category. RESULTS: The overall differences between CA and EA for Willems' method in boys and girls were 0.06 and - 0.02, respectively. For Demirjian's method, the differences were 0.60 and 0.74, respectively. The overestimations of Demirjian's method were statistically significant (p < 0.001). Willems' method reached the best outcomes among children between 3 and 12 years, while Demirjian's best performances were between the ages of 7 and 10 years. CONCLUSION: Willems' method led to differences between CA and AE that were acceptable for clinical and forensic practice. CLINICAL RELEVANCE: Age estimation may guide clinical decisions based on treatment timing. Validating international tools is necessary to promote evidence-based practice and country-specific application. This study overcame the limitations of previous research to provide a more realistic perspective of the performance of age estimation methods in Brazilian children. Willems' method had a superior performance compared to Demirjian's method and led to outcomes that were better than most studies with the Brazilian population.

Evaluation of the Nasopalatine Canal of Patients With and Without Cleft Lip and Palate in CBCT Exams.

OBJECTIVE: To identify and compare the morphology and dimensions of the nasopalatine canal (NPC) of individuals with and without cleft lip and palate using Conical Beam Computed Tomography (CBCT) images and to relate the results to the type of cleft and tooth absences in the region. SETTING: This is a cross-sectional, analytical study with a retrospective sample. PATIENTS, PARTICIPANTS: 100 CBCT exams from patients with cleft lip and palate and 100 CBCT exams from patients without cleft lip and palate were used. INTERVENTIONS: The NPC was evaluated for its morphology and measurements in the coronal, sagittal, and axial reformatting of CBCT exams. RESULTS: It was obtained as a result that in the group of patients with a cleft, the shapes of funnel, banana, and needle of the NPC were more frequent than in the control group. Patients with cleft lip and palate had significantly a larger nasopalatine foramen and a larger NPC diameter, besides a significantly shorter NPC, compared to controls. In both groups, edentulous patients had less anterior maxillary bone thickness, when compared to patients with maxillary anterior teeth. Patients with clefts had a bone thickness buccal to the NPC less than in the control group. CONCLUSIONS: This study confirms the anatomical variability of NPC in patients with cleft lip and palate. This finding reinforces the need for thorough surgical planning of the anterior region of the maxilla, in CBCT exams, by the dentist.

Evidence of validity of the revised Helping Alliance Questionnaire based on the internal structure in a Brazilian clinical sample.

The revised Helping Alliance Questionnaire (HAq-II) is among the most used instruments that measure therapeutic alliance. Despite its use in research, this instrument is not validated for the Brazilian population. The aim of this study was to explore the evidence of validity of the HAq-II based on the internal structure in a sample of Brazilian psychiatric patients. An ambulatory convenience sample of 204 patients with major depressive disorder (MDD) and 81 patients with obsessive-compulsive disorder (OCD) was randomized between two different types of treatment. The HAq-II was completed by patients (patient version) and by 33 therapists who performed the interventions (therapist version) between the second and third sessions. We used confirmatory factor analysis (CFA) to investigate two models: (1) a one-dimensional therapeutic alliance model and (2) a two-dimensional model considering the factors 'positive alliance' and 'negative alliance'. The internal consistency of the HAq-II was measured by Cronbach's alpha. To investigate discriminant validity, we used the t-test for independent samples, ANOVA and Pearson's correlation coefficient. The analysis showed that the best model of the instrument was one-dimensional. Cronbach's alpha for both versions displayed values above 0.89. The Brazilian version of the HAq-II presented properties similar to those found in the original version. However, studies related to the one-dimensional model with other samples are necessary.

Tomato phytochromes B1 and B2 are part of the responses to the nutritional stress induced by NPK deficiency.

Phytochromes are red-light photoreceptors that play an important role in regulating many responses of plants, including its nutritional control. Nutrient deficiency in plants has become a constraint for agricultural production; thus, we investigated the role of phytochromes B1 and B2 in the nutritional, physiological, and growth changes of the control genotype (WT) and both phyB1 and phyB2 tomato mutants (deficient in phyB1 and phyB2) under nutritional sufficiency and individual deficiency of N, P, and K. Under complete solution, the plants of phyB1 and phyB2 had a decreased N, P, and K accumulation compared with WT and consequently a reduced content of chlorophyll and carotenoids, and dry weight production. In the condition of N deficiency, phyB1 had decreased N absorption, pigments concentration, and plant dry weight, while increased oxidative stress of membranes (MDA content). Similarly, phyB2 also had reduced N absorption. The deficiency of phyB1 mitigated the effects of P deficiency as phyB1 mutant had improved nutritional and physiological responses, increasing plant dry weight production. In contrast, phyB2 reduced N accumulation, quantum efficiency of photosystem II (Fv/Fm), and the concentration of pigments, while it increased MDA. Under K deficiency, phyB1 displayed a reduced P accumulation, as well as the total concentration of chlorophylls and carotenoids and K use efficiency. An increased concentration of MDA was found in phyB2 plants, as well as a reduction in chlorophylls concentration and in the use efficiency of K. Together, these results indicate a new perspective on the control of phytochromes in the nutrition of tomato plants under nutritional stress.

Periodontal status, vascular reactivity, and platelet aggregation changes in rats submitted to hypercholesterolemic diet and periodontitis.

BACKGROUND AND OBJECTIVES: Periodontitis can corroborate with development and progression of atherosclerosis and a possible bidirectional interaction between both pathologies has been hypothesized. The aim of this work was to study the interactions between diet-induced hypercholesterolemia and ligature-induced periodontitis in Wistar rats submitted to both conditions. MATERIAL AND METHODS: Animals were divided into four experimental groups: C (control: standard diet without periodontitis), Perio (periodontitis plus standard diet), HC (high cholesterol diet without periodontitis), and HC + Perio (high cholesterol diet plus periodontitis). The diets were offered for 45 days and a silk ligature was applied in the lower first molars of Perio and HC-Perio animals on day 34 and maintained for 11 days until euthanasia. The mandibles were excised, and alveolar bone loss was determined by macroscopic and micro-tomographic (µ-CT) imaging. Blood samples were obtained, and platelet aggregation was induced in plasma rich in platelets by adenosine diphosphate (ADP) and collagen. Endothelium-dependent vascular reactivity and protein expression of endothelial (eNOS), phosphorylated endothelial (peNOS), and inducible (iNOS) nitric oxide synthases were evaluated in aorta samples. RESULTS: The HC diet combined with periodontitis (HC + Perio group) was associated with an increased alveolar bone loss, when compared to the other groups. Both in Perio and HC groups, platelet aggregation induced by ADP or collagen was increased, while maximum aortic relaxation induced by acetylcholine was decreased. Periodontitis or HC diet alone decreased the expression of peNOS and HC diet increased the expression of iNOS. In contrast, no additive or synergistic effects were found in vascular reactivity or in platelet aggregation when the two conditions were associated (HC + Perio group). CONCLUSION: Hypercholesterolemia accelerated the process of bone loss induced by periodontitis while a high cholesterol diet or periodontitis individually increased platelet aggregation and vascular reactivity in rats without additive or synergistic effects, when associated.

Relationship between trabecular bone architecture and early dental implant failure in the posterior region of the mandible.

OBJECTIVE: To investigate the relationship between preoperative trabecular bone structure and implant outcome based on bone morphometric bone parameters from CBCT scans. MATERIALS AND METHODS: Twenty consecutive cases with early implant failure in the posterior region of the mandible were matched with 20 control patients with a successful implant osseointegration selected. All patients had taken a preoperative CBCT image according to a standardized acquisition protocol. On these CBCT scans, the trabecular bone of each implantation site was selected and segmented, after which 3D morphometric bone parameters were calculated and used in a cluster analysis to objectively differentiate trabecular bone patterns. Fisher's exact test was used to determine whether there is a significant association between trabecular pattern and implant outcome. RESULTS: A sparse, intermediate, and dense trabecular bone pattern was distinguished by cluster analysis. The relationship between the trabecular bone pattern and early implant failure was significant (z = 9.6; p < .05). Early implant failure was more likely to occur in the sparse bone types, while implant survival was associated with intermediate bone types. CONCLUSION: Prior to implant placement, attention should be given to extreme deviations in trabecular structure at the planned implant sites. Very sparse or very dense bone should be carefully evaluated at the potential implant site, while intermediate bone types seem favorable for implant survival.

The use of apocynin inhibits osteoclastogenesis.

Reactive oxygen species (ROS) are produced by NADPH oxidase (NOX), an enzyme that reduces oxygen by using NADPH as a substrate. Apocynin (APO) is a catechol that is used as a NOX inhibitor, and N-acetyl-cysteine ​​(NAC) can reduce intracellular ROS levels. In this work, the effect of APO and NAC on osteoclast formation were evaluated. APO and NAC significantly decreased the number of tartrate-resistant acid phosphatase (TRAP)-positive cells and the osteoclast area. We analyzed bone-marrow derived monocyte-macrophages (BMMs) that differentiated into osteoclasts after RANKL stimulation. Stimulation was associated with either APO or NAC treatment and osteoclastogenesis marker expression, including NFATc1, MMP-9, and DC-STAMP, was evaluated. APO decreased the intracellular calcium concentration by calcium channels other than ITPR1 and TPC2. On the other hand, APO reduced Tnfrsf11a (RANK) expression and did not alter Fam102a (EEIG1) expression. Therefore, our results demonstrate that APO inhibits osteoclastogenesis by the RANK-RANKL-related signaling pathways, decreases osteoclast markers, and reduces intracellular calcium concentration.

Tunicate Heparan Sulfate Enriched in 2-Sulfated ß-Glucuronic Acid: Structure, Anticoagulant Activity, and Inhibitory Effect on the Binding of Human Colon Adenocarcinoma Cells to Immobilized P-Selectin.

Heparin or highly sulfated heparan sulfate (HS) has been described in different invertebrates. In ascidians (Chordata-Tunicata), these glycosaminoglycans occur in intracellular granules of oocyte accessory cells and circulating basophil-like cells, resembling mammalian mast cells and basophils, respectively. HS is also a component of the basement membrane of different ascidian organs. We have analyzed an HS isolated from the internal organs of the ascidian Phallusia nigra, using solution 1H/13C NMR spectroscopy, which allowed us to identify and quantify the monosaccharides found in this glycosaminoglycan. A variety of α-glucosamine units with distinct degrees of sulfation and N-acetylation were revealed. The hexuronic acid units occur both as α-iduronic acid and ß-glucuronic acid, with variable sulfation at the 2-position. A peculiar structural aspect of the tunicate HS is the high content of 2-sulfated ß-glucuronic acid, which accounts for one-third of the total hexuronic acid units. Another distinct aspect of this HS is the occurrence of high content of N-acetylated α-glucosamine units bearing a sulfate group at position 6. The unique ascidian HS is a potent inhibitor of the binding of human colon adenocarcinoma cells to immobilized P-selectin, being 11-fold more potent than mammalian heparin, but almost ineffective as an anticoagulant. Thus, the components of the HS structure required to inhibit coagulation and binding of tumor cells to P-selectin are distinct. Our results also suggest that the regulation of the pathway involved in the biosynthesis of glycosaminoglycans suffered variations during the evolution of chordates.

Antimicrobial photodynamic therapy as adjunct to non-surgical periodontal treatment in smokers: a randomized clinical trial.

OBJECTIVES: This study aims to investigate the additional influence of multiple applications of antimicrobial photodynamic therapy (aPDT) in smokers with chronic periodontitis. MATERIALS AND METHODS: Twenty smokers with chronic periodontitis were treated in a split-mouth design study with aPDT adjunct to Scaling and Root Planing (SRP) or SRP. aPDT was performed by using a laser light source with 660 nm wavelength associated with a photosensitizer. The applications were performed in four episodes (at days 0, 2, 7, and 14). All patients were monitored for 90 days. Plaque index, probing depth, clinical attachment level, and bleeding on probing were performed at baseline, 30, and 90 days after the SRP. Gingival crevicular fluid and subgingival plaque samples were collected for immunological and microbiological analysis, respectively. Data obtained were statistically analyzed. RESULTS: aPDT as an adjunct to SRP did not demonstrate statistically significant advantages on clinical parameters when compared with SRP alone. No statistic significant differences between groups were observed (p < 0.05). Levels of anti-inflammatory cytokines and bacterial species were comparable in both groups at day 90 after treatment. CONCLUSION: Periodontal treatment with SRP + aPDT in multiples episodes was not able to promote additional clinical, immunological, and microbiological benefits in smokers when compared SRP alone in patients with chronic periodontitis. CLINICAL RELEVANCE: Multiple episodes of aPDT adjunctive to non-surgical treatment did not improve significantly the clinical, immunological, and microbiological parameters when compared with SRP alone. More randomized clinical trials are needed to evaluate adjuvant therapies for scaling and root planning in smokers with chronic periodontitis. ClinicalTrials.gov Identifier: NCT03039244.

Effects of Bifidobacterium probiotic on the treatment of chronic periodontitis: A randomized clinical trial.

AIM: This randomized placebo-controlled clinical trial evaluated the effect of Bifidobacterium animalis subsp. lactis (B. lactis) HN019-containing probiotic lozenges as adjuvant to scaling and root planing (SRP) in patients with generalized chronic periodontitis. MATERIALS AND METHODS: Forty-one chronic periodontitis patients were recruited and monitored clinically, immunologically, and microbiologically at baseline (before SRP) and 30 and 90 days after SRP. All patients were randomly assigned to a Test (SRP + Probiotic, n = 20) or Control (SRP + Placebo, n = 21) group. The probiotic lozenges were used twice a day for 30 days. The data were statistically analysed. RESULTS: The Test group presented a decrease in probing pocket depth and a clinical attachment gain significantly higher than those of the Control group at 90 days. The Test group also demonstrated significantly fewer periodontal pathogens of red and orange complexes, as well as lower proinflammatory cytokine levels when compared to the Control group. Only the Test group showed an increase in the number of B. lactis HN019 DNA copies on subgingival biofilm at 30 and 90 days. CONCLUSION: The use of B. lactis HN019 as an adjunct to SRP promotes additional clinical, microbiological, and immunological benefits in the treatment of chronic periodontitis (NCT03408548).

Comparison of Clinical Significance of Cognitive-Behavioral Therapy and Psychodynamic Therapy for Major Depressive Disorder: A Randomized Clinical Trial.

The aim of this study was to evaluate the effect of two brief psychotherapy models for major depressive disorder (MDD). This is a randomized clinical trial with 247 individuals diagnosed with MDD. Supportive-expressive dynamic psychotherapy (SEDP) (18 sessions) and cognitive-behavioral therapy (CBT) (16 sessions) were the two models used in this study. Participants were evaluated at baseline, during treatment, and postintervention (last session). Clinically significant changes were found in both psychotherapy models, and CBT showed higher response rates. Regarding the Beck Depression Inventory-II [F(1,120) = 4.07, p = 0.046] and Outcome Questionnaire 45.2 [F(1.114) = 7.99, p = 0.006], CBT had a better effect than SEDP. Hence, the results obtained have contributed to literature, served to corroborate the importance and effectiveness of psychodynamic psychotherapy, as well as explored the mechanisms of change, remission, and response in the treatment of MDD, which have been ignored to a large extent.