The Importance of Complement-Mediated Immune Signaling in Alzheimer's Disease Pathogenesis.

As an essential component of our innate immune system, the complement system is responsible for our defense against pathogens. The complement cascade has complex roles in the central nervous system (CNS), most of what we know about it stems from its role in brain development. However, in recent years, numerous reports have implicated the classical complement cascade in both brain development and decline. More specifically, complement dysfunction has been implicated in neurodegenerative disorders, such as Alzheimer's disease (AD), which is the most common form of dementia. Synapse loss is one of the main pathological hallmarks of AD and correlates with memory impairment. Throughout the course of AD progression, synapses are tagged with complement proteins and are consequently removed by microglia that express complement receptors. Notably, astrocytes are also capable of secreting signals that induce the expression of complement proteins in the CNS. Both astrocytes and microglia are implicated in neuroinflammation, another hallmark of AD pathogenesis. In this review, we provide an overview of previously known and newly established roles for the complement cascade in the CNS and we explore how complement interactions with microglia, astrocytes, and other risk factors such as TREM2 and ApoE4 modulate the processes of neurodegeneration in both amyloid and tau models of AD.

Impact of CAD/CAM burs lifetime on surface properties of dental zirconia: Implications for biocompatibility of custom abutments.

OBJECTIVE: To evaluate the effect of the deterioration of computer aided design/computer aided manufacturing (CAD/CAM) burs during zirconia milling, on surface roughness, contact angle, and fibroblast viability. MATERIALS AND METHODS: Ceramic blocks were milled and 75 ceramic disks (8 × 1.5 mm) made and allocated into three groups (n = 25): G1-brand new 2L and 1L burs, G2-2L bur at the end of lifetime and brand new 1L bur and G3-both burs at the end of their lifetimes. Roughness (Ra, Rq, and Rz) was evaluated using a 3D optical profilometer, the contact angle by the sessile drop method and the cell viability of the mouse NIH/3T3 fibroblast, using the Alamar Blue assay at intervals of 24, 48, and 72 h (ISO 10993-5). Data were analyzed by one-way ANOVA and Kruskal-Wallis tests (p ≤ 0.05). RESULTS: Roughness increased as the burs deteriorated and G3 (0.27 ± 0.04) presented a higher value for Ra (p < 0.001). The highest contact angle was observed in G3 (86.2 ± 2.66) when compared with G1 (63.7 ± 12.49) and G2 (75.3 ± 6.36) (p < 0.001). Alamar Blue indicated an increase in cell proliferation, with no significant differences among the groups at 24 and 72 h (p > 0.05). CONCLUSIONS: The deterioration of the burs increased the surface roughness and decreased the wettability, but did not interfere in cell viability and proliferation. CLINICAL SIGNIFICANCE: The use of custom zirconia abutments represents an effective strategy for single crowns restorations. Our findings suggest that these abutments can be efficiently milled using CAD/CAM burs within their recommended lifetime.

Effectiveness of different surface treatments on bond strength between 3D-printed teeth and denture base.

PURPOSE: To investigate the effects of different surface treatments and thermal cycling on the shear bond strength between 3D-printed teeth and denture bases. MATERIAL AND METHODS: For the shear bond strength (SBS) test, the specimens were the maxillary central incisors (11 × 9 × 7 mm) bonded on a cylindrical base (20 × 25 mm). The control group was heat-cured polymethylmethacrylate (PMMA) (N = 20). The printed group was divided into five subgroups (N = 20): no treatment, sandblasting with aluminum oxide (Al2O3), methyl methacrylate monomer, acetone, and adhesive with urethane dimethacrylate. Half of the samples were subjected to 2000 thermal cycling cycles, and all samples were subjected to the SBS test. The failure mode was established as adhesive, cohesive, or mixed through stereomicroscopic analysis. The surface roughness test (Sa) was performed using optical profilometry, and the rectangular specimens (14 × 14 × 2.5 mm) were divided into four groups according to the surface treatments (N = 7 per group). Paired T and Wilcoxon tests were conducted to perform comparisons within the same group. The Kruskal-Wallis and Dwass-Steel-Critchlow-Fligner post-hoc tests were conducted to compare the groups. RESULTS: Al2O3 sandblasting in the 3D-printed groups achieved high SBS values comparable to those of the control group in the thermal cycled (p = 0.962) and non-thermal cycled samples (p = 0.319). It was the only treatment capable of modifying the surface of the 3D-printed resin, thereby increasing the roughness (p = 0.016). CONCLUSIONS: Sandblasting is recommended to increase the bond strength between the tooth and denture bases.

Linear and areal surface roughness assessments for the study of tooth wear in human enamel.

OBJECTIVES: To test 8 models of linear surface roughness assessment in characterizing surface profile description and to correlate these models with equivalent areal parameters over sound human enamel in vitro. MATERIALS AND METHODS: Thirty enamel blocks were randomly selected. The roughness data (2D-Rp; Rv; Rz; Rc; Rt; Ra; Rq; Rsk; Rku/3D-Sp; Sv; Sz; Sa; Sq; Ssk; Sku) was obtained in duplicate in a non-contact 3D optical profilometer. The models were composed by 1 single vertical trace (model 1) until 8 traces (model 8 composed by three vertical traces, three horizontal traces, and two diagonal). RESULTS: The addition of linear sampling traces to the enamel blocks did not result in Rp, Rv, Rz, Rc, Rt, Ra, Rq, Rsk, and Rku value changes (low power-from 5 to 72%). Significant Spearman's correlation coefficients were obtained in most correlation analysis (Rp ↔ Sp; Rv ↔ Sv; Rz ↔ Sz; Ra ↔ Sa; Rq ↔ Sq; and Rku ↔ Sku). CONCLUSIONS: A single vertical trace in the middle of the sample was representative of the overall enamel surface roughness (Rp, Rv, Rz, Rc, Rt, Ra, Rq, Rsk, and Rku) models. The majority of the assessed models in the correlation evaluation presented significant and positive association. CLINICAL RELEVANCE: The findings highlight the applicable model for roughness analysis over human enamel recommended for research and in situ trials assessments.

APOE and immunity: Research highlights.

INTRODUCTION: At the Alzheimer's Association's APOE and Immunity virtual conference, held in October 2021, leading neuroscience experts shared recent research advances on and inspiring insights into the various roles that both the apolipoprotein E gene (APOE) and facets of immunity play in neurodegenerative diseases, including Alzheimer's disease and other dementias. METHODS: The meeting brought together more than 1200 registered attendees from 62 different countries, representing the realms of academia and industry. RESULTS: During the 4-day meeting, presenters illuminated aspects of the cross-talk between APOE and immunity, with a focus on the roles of microglia, triggering receptor expressed on myeloid cells 2 (TREM2), and components of inflammation (e.g., tumor necrosis factor α [TNFα]). DISCUSSION: This manuscript emphasizes the importance of diversity in current and future research and presents an integrated view of innate immune functions in Alzheimer's disease as well as related promising directions in drug development.

Antimicrobial effect and the mechanical and surface properties of a self-disinfecting and a chlorhexidine-incorporated Type IV dental stone.

STATEMENT OF PROBLEM: Stone casts are subject to contamination, but whether disinfectants incorporated into the stone are effective is unclear. PURPOSE: The purpose of this in vitro study was to evaluate the antimicrobial activity and the mechanical and surface properties of self-disinfecting gypsum (SDG) and gypsum mixed with 2% chlorhexidine (GCHX). MATERIAL AND METHODS: Antimicrobial action was evaluated using the diffusion-disk technique on Streptococcus aureus and Candida albicans 1 hour and 24 hours after pouring the gypsum. The groups were SDG, GCHX, a positive control (PC) of gypsum mixed with distilled water, and a negative control (NC) of filter paper disk soaked with 2% chlorhexidine; n=8. Inhibition halos were measured using the ImageJ software program and statistically analyzed using the repeated measures mixed ANOVA with time×group interaction. Compressive strength (CS) in MPa and surface roughness (SR) in µm (parameters: Ra - roughness average; and Sa - 3-dimensional (3D) arithmetic mean of the surface profile) tests were performed to characterize the specimens (evaluated groups: SDG, GCHX, and PC; n=10). CS data were analyzed by a 2-way ANOVA with time×group interaction, and SR data by a 1-way ANOVA (α=.05). RESULTS: For S aureus, there were differences between GCHX and SDG at 1 hour and 24 hours (P<.05), but no significant differences were found for C albicans (P>.05). GCHX was better than PC, except for C albicans, and showed a reduction in CS when compared with PC and SDG (P<.05) at all time intervals. The SR of GCHX increased (Ra:1.76, Sa:2.08) when compared with PC (Ra:0.89, Sa:1.12) and SDG (Ra:1.03, Sa:1.35) (Ra: P<.004 and Sa: P<.001). CONCLUSIONS: The antimicrobial activity of GCHX against S aureus was better than that of SDG, but neither had an effect against C albicans. As for CS and SR, GCHX presented a decrease in properties when compared with PC and SDG but was within the American Dental Association #25 specification values.

Effect of simulated brushing with dentifrices on surface roughness and the mass loss of acrylic resin: A systematic review and meta-analysis of in vitro studies.

STATEMENT OF PROBLEM: Brushing with dentifrice is the most commonly used denture cleaning method. However, it can result in the mass loss of acrylic resin and an increase in surface roughness, which favors the adherence of microorganisms. PURPOSE: The purpose of this systematic review and meta-analysis of in vitro studies was to assess the influence of simulated brushing by using dentifrices and water on surface roughness and the mass loss of acrylic resins. MATERIAL AND METHODS: Searches were performed in PubMed, Scopus, Web of Science, Lilacs, Embase, Open Gray, and Google Scholar databases in September 2022. The study selection process, data extraction, and risk of bias analysis were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The protocol of this systematic review was registered in the Open Science Framework (DOI number 10.17605/OSF.IO/QD4GH). Meta-analysis was performed by using a random effects model (α=.05) in the RevMan (Cochrane Collaboration) software program. RESULTS: A total of 14 studies were included in the qualitative synthesis and 2 studies in the quantitative synthesis. The manual toothbrush was the most analyzed (n=9), followed by the electric toothbrush (n=5) and denture brush (n=1). Denture base resin (n=8) was evaluated more than acrylic resin for the abrasiveness of toothpaste (n=6). Most studies used conventional toothpaste (n=12), whereas 6 used specific dentifrices. The period of brushing corresponding to 1 year was the most predominant (n=6). Surface roughness (n=13) was evaluated more than mass loss (n=4). In general, dentifrices resulted in greater surface roughness than water. According to meta-analysis results, brushing by using dentifrices reported higher mass loss values than brushing with distilled water (P<.05). CONCLUSIONS: Brushing acrylic resins with dentifrice was more abrasive than brushing with water.

Longevity of bulk fill and ormocer composites in permanent posterior teeth: Systematic review and meta-analysis.

PURPOSE: To evaluate the clinical longevity of bulk-fill resins and ormocer composites compared to conventional nanofill and nanohybrid resins in posterior permanent teeth. METHODS: PubMed, Web of Science, Scopus, Science Direct, Cochrane Library, and Scielo were electronically searched for randomized clinical trials, without language restrictions. The extracted data were analyzed using Review Manager, comparing the clinical behavior of bulk fill or ormocer restorations with nanofill or nanohybrid resins. Statistical analysis was performed with a significance level of 5% for all analyses (P= 0.05). The risk of bias was assessed using the Cochrane assessment tool. RESULTS: 11 randomized clinical trials were included, with an average follow-up time of 40.36 months. A total of 812 restorations were evaluated and 58 failures were analyzed: 18 of the 253 bulk-fill restorations (7.11%), 21 of the 173 (12.3%) ormocer restorations, and 20 of the 386 (5.18%) control group (nanofill or nanohybrid composites) restorations failed. In the meta-analysis, there was no significant difference between the bulk-fill and the control group (statistical power = 24.38%; P= 0.206; IC = 95%); whereas, when comparing between ormocer and control group, the control group exhibited better performance (statistical power = 81.62%; P= 0.0042; IC = 95%). CLINICAL SIGNIFICANCE: Conventional nanofill and nanohybrid resins exhibited better clinical longevity than ormocer composites in posterior restorations, but when compared to bulk fill, they had similar performance.

Effects of long-term cinnamaldehyde immersion on the surface roughness and color of heat-polymerized denture base resin.

STATEMENT OF PROBLEM: Cinnamaldehyde has been successfully used for the short-term disinfection of dentures; however, its long-term effects on the surface and color properties of denture base materials remain unknown. PURPOSE: The purpose of this in vitro study was to evaluate the effects of simulated immersion in cinnamaldehyde for up to 5 years on the surface roughness and color parameters of a heat-polymerized denture resin. MATERIAL AND METHODS: Eighty Ø10×5-mm disk-shaped specimens were prepared from microwave heat-polymerized polymethylmethacrylate (PMMA) and immersed in 4 solutions (n=20): TW-tap water (control), SH - 0.5% sodium hypochlorite, PX-alkaline peroxide, and CA-cinnamaldehyde (27 µg/mL). The immersion protocol simulated 104 cycles (3.5 months), 913 cycles (2.5 years), and 1825 immersion cycles (5 years) of a daily immersion cleaning protocol, with immersion times ranging from 10 to 20-minutes. Surface roughness (Sa) and the color parameters of CIELab (L∗ a∗ b∗, ΔEab), CIEDE2000 (ΔE00), and the National Bureau of Standards (NBS) were analyzed at baseline (t=0) and after the immersion cycles. The data were analyzed by 2-way analysis of variance (ANOVA) for repeated measures and the Tukey post hoc test (α=.01). RESULTS: Sa was significantly increased in all groups after 1825 cycles compared with baseline (P<.01), regardless of the solution. Only the time factor significantly affected ΔEab, ΔE00, and NBS parameters, which were below the perceptibility and acceptability thresholds. After a simulated 5-year immersion, the surface roughness and color values of CA-treated specimens were not statistically different from those of the other groups (P>.01). CONCLUSIONS: Cinnamaldehyde solution (27 µg/mL) produced minor effects on the surface roughness and color parameters of a heat-polymerized denture base resin similar to those of 0.5% sodium hypochlorite and alkaline peroxide after a 5-year simulated immersion.

Interleukin-1ß mediates alterations in mitochondrial fusion/fission proteins and memory impairment induced by amyloid-ß oligomers.

BACKGROUND: The lack of effective treatments for Alzheimer's disease (AD) reflects an incomplete understanding of disease mechanisms. Alterations in proteins involved in mitochondrial dynamics, an essential process for mitochondrial integrity and function, have been reported in AD brains. Impaired mitochondrial dynamics causes mitochondrial dysfunction and has been associated with cognitive impairment in AD. Here, we investigated a possible link between pro-inflammatory interleukin-1 (IL-1), mitochondrial dysfunction, and cognitive impairment in AD models. METHODS: We exposed primary hippocampal cell cultures to amyloid-ß oligomers (AßOs) and carried out AßO infusions into the lateral cerebral ventricle of cynomolgus macaques to assess the impact of AßOs on proteins that regulate mitochondrial dynamics. Where indicated, primary cultures were pre-treated with mitochondrial division inhibitor 1 (mdivi-1), or with anakinra, a recombinant interleukin-1 receptor (IL-1R) antagonist used in the treatment of rheumatoid arthritis. Cognitive impairment was investigated in C57BL/6 mice that received an intracerebroventricular (i.c.v.) infusion of AßOs in the presence or absence of mdivi-1. To assess the role of interleukin-1 beta (IL-1ß) in AßO-induced alterations in mitochondrial proteins and memory impairment, interleukin receptor-1 knockout (Il1r1-/-) mice received an i.c.v. infusion of AßOs. RESULTS: We report that anakinra prevented AßO-induced alteration in mitochondrial dynamics proteins in primary hippocampal cultures. Altered levels of proteins involved in mitochondrial fusion and fission were observed in the brains of cynomolgus macaques that received i.c.v. infusions of AßOs. The mitochondrial fission inhibitor, mdivi-1, alleviated synapse loss and cognitive impairment induced by AßOs in mice. In addition, AßOs failed to cause alterations in expression of mitochondrial dynamics proteins or memory impairment in Il1r1-/- mice. CONCLUSION: These findings indicate that IL-1ß mediates the impact of AßOs on proteins involved in mitochondrial dynamics and that strategies aimed to prevent pathological alterations in those proteins may counteract synapse loss and cognitive impairment in AD.

Nanoparticle-modified PMMA to prevent denture stomatitis: a systematic review.

This systematic review aimed to evaluate the antifungal effectiveness of polymethylmetacrylate (PMMA) modified by nanoparticles (NPs) and to compare it with conventional acrylic resins for denture bases. The present study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Searches were performed using PubMed, SCOPUS, SciELO, EMBASE, and LILACS. Eligibility criteria were as recommended by PRISMA. The studies presented great variability regarding NP type, synthesis method, antifungal evaluation method, and antifungal effect. The most commonly used NPs were silver (AgNP) and zinc oxide (ZnONP), ranging in size from 10 to 100 nm. The incorporation methods were mechanical or agitated. Despite PMMA modification by ZnONP being shown in vitro to be a combination with the best antifungal effect, future studies are still needed to determine the minimum inhibitory concentration for Candida spp. and assess its biocompatibility before the protocol is clinically tested.

Cause-specific mortality prediction in older residents of São Paulo, Brazil: a machine learning approach.

BACKGROUND: Populational ageing has been increasing in a remarkable rate in developing countries. In this scenario, preventive strategies could help to decrease the burden of higher demands for healthcare services. Machine learning algorithms have been increasingly applied for identifying priority candidates for preventive actions, presenting a better predictive performance than traditional parsimonious models. METHODS: Data were collected from the Health, Well Being and Aging (SABE) Study, a representative sample of older residents of São Paulo, Brazil. Machine learning algorithms were applied to predict death by diseases of respiratory system (DRS), diseases of circulatory system (DCS), neoplasms and other specific causes within 5 years, using socioeconomic, demographic and health features. The algorithms were trained in a random sample of 70% of subjects, and then tested in the other 30% unseen data. RESULTS: The outcome with highest predictive performance was death by DRS (AUC-ROC = 0.89), followed by the other specific causes (AUC-ROC = 0.87), DCS (AUC-ROC = 0.67) and neoplasms (AUC-ROC = 0.52). Among only the 25% of individuals with the highest predicted risk of mortality from DRS were included 100% of the actual cases. The machine learning algorithms with the highest predictive performance were light gradient boosted machine and extreme gradient boosting. CONCLUSION: The algorithms had a high predictive performance for DRS, but lower for DCS and neoplasms. Mortality prediction with machine learning can improve clinical decisions especially regarding targeted preventive measures for older individuals.

Neonatal mortality prediction with routinely collected data: a machine learning approach.

BACKGROUND: Recent decreases in neonatal mortality have been slower than expected for most countries. This study aims to predict the risk of neonatal mortality using only data routinely available from birth records in the largest city of the Americas. METHODS: A probabilistic linkage of every birth record occurring in the municipality of São Paulo, Brazil, between 2012 e 2017 was performed with the death records from 2012 to 2018 (1,202,843 births and 447,687 deaths), and a total of 7282 neonatal deaths were identified (a neonatal mortality rate of 6.46 per 1000 live births). Births from 2012 and 2016 (N = 941,308; or 83.44% of the total) were used to train five different machine learning algorithms, while births occurring in 2017 (N = 186,854; or 16.56% of the total) were used to test their predictive performance on new unseen data. RESULTS: The best performance was obtained by the extreme gradient boosting trees (XGBoost) algorithm, with a very high AUC of 0.97 and F1-score of 0.55. The 5% births with the highest predicted risk of neonatal death included more than 90% of the actual neonatal deaths. On the other hand, there were no deaths among the 5% births with the lowest predicted risk. There were no significant differences in predictive performance for vulnerable subgroups. The use of a smaller number of variables (WHO's five minimum perinatal indicators) decreased overall performance but the results still remained high (AUC of 0.91). With the addition of only three more variables, we achieved the same predictive performance (AUC of 0.97) as using all the 23 variables originally available from the Brazilian birth records. CONCLUSION: Machine learning algorithms were able to identify with very high predictive performance the neonatal mortality risk of newborns using only routinely collected data.

Is there an association between rheumatoid arthritis and bone changes in the temporomandibular joint diagnosed by cone-beam computed tomography? A systematic review and meta-analysis.

OBJECTIVES: Evaluate the relation of rheumatoid arthritis (RA) and bone changes in the temporomandibular joint diagnosed by cone-beam computed tomography (CBCT). MATERIALS AND METHODS: This systematic review and meta-analysis were recorded in the PROSPERO database, using the CRD42020153246 protocol. The electronic searches were performed in the following databases: Pubmed, Scopus, Web of Science, Lilacs, Cochrane, and Open Grey. Cross-sectional studies that evaluated patients with RA with bone changes in the temporomandibular joint diagnosed by CBCT, without language restriction or publication date, were included. Meta-analysis was performed in Stata Software (StataCorp, TX, USA, version 12.0), using the metan, and a random effects model, and the risk of different bone alterations occurring in adults with and without arthritis was estimated using odds ratios (ORs) as a pooled measure of effect. Forest plots were used to present the isolated and the pooled effects (ORs and 95% CI). RESULTS: Six studies were used for qualitative synthesis and 2 studies for quantitative synthesis. All studies diagnosed higher prevalence changes in the bone structures of the TMJ of RA patients, described as erosion, flattening, sclerosis, and osteophytes. Meta-analysis showed that the chance of bone changes occurring in components of the TMJ is greater in individuals who have RA. CONCLUSION: There is an association between RA and bone changes in TMJ structures diagnosed through CBCT, as RA patients were more likely to have osteoarthritic changes in this joint. CLINICAL RELEVANCE: Understanding the existence of an association between bone alterations in TMJ and RA can assist in the management of patients.

Effectiveness of denture microwave disinfection for treatment of denture stomatitis: A systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review was to evaluate the effectiveness of removable complete denture disinfection using microwaves for the treatment of denture stomatitis. METHODS: This review identified studies comparing the efficacy of microwave prosthesis disinfection (I) to topical antifungal therapy (C) in the treatment of denture stomatitis (O), which included only individuals who used complete dentures and presented with denture stomatitis (P). The search was performed in six databases and identified 1524 records; after the removal of duplicates, 816 articles remained. Three articles were selected for qualitative synthesis and two for meta-analysis. Random-effects meta-analysis estimated the polled effects of microwave disinfection and antifungal therapy on the Candida counts and clinical manifestation of denture stomatitis. The GRADE approach was used to estimate the certainty of evidence. RESULTS: All included studies reported significant reductions in Candida counts and the frequency of denture stomatitis of groups subjected to microwave disinfection of dentures and topical antifungal therapy with nystatin. Significative differences between treatments were only detected for Candida quantification in the palate, within 90 days follow-up period (SMD = 0.47, 95% CI = 0.02-0.91). Meta-analyses did not show any further differences between treatments (p > .05), considering the Candida quantification in dentures and the frequency of clinical signs of denture stomatitis. The certainty of the evidence was considered as low, according to GRADE approach. CONCLUSION: Microwave disinfection of complete dentures can be considered as efficient as antifungal therapy for the treatment of denture stomatitis. However, further well-designed studies are necessary to confirm such evidence.

Photobiostimulation activity of different low-level laser dosage on masticatory muscles and temporomandibular joint in an induced arthritis rat model.

This study aimed to investigate the anti-inflammatory effects of different dosage of low-level laser therapy (LLLT) in an experimental model of temporomandibular joint (TMJ) arthritis. One hundred male Wistar rats were used and divided into the following groups: CG, control group; AG, animals group with left TMJ arthritis induced by intra-articular injection of Complete Freund's adjuvant - CFA; LG5, LG10 and LG20 - animals with arthritis and treated with LLLT at doses 5, 10, and 20 J/cm2, respectively. Morphological analysis was performed by TMJ histological sections stained with hematoxylin-eosin (HE), picrosirius (PSR), and toluidine blue (TB), as well as histomorphometric evaluation of cartilage, articular disc, and masticatory muscles. The amount of feed consumed within 3 weeks was evaluated, and biochemical analysis of TMJ tissues included measurement of sulfated glycosaminoglycans (GAGs), matrix metalloproteinases (MMPs) 2 and 9 zymography, and ELISA for cytokines IL-6, TNF-α, and IL-1ß. Only the 20 J/cm2 dose promoted higher feed intake compared to AG. On the other hand, all LLLT doses promoted better organization of articular disc collagen fibers, greater number of proteoglycans in articular cartilage, increased area and diameter of left lateral pterygoid fibers, reduced latent and active MMP 9 and 2 activity, and lower IL-1ß concentration compared to AG. Considering the study limitations, it was observed that LLLT treatments were effective in protecting and tissue cleansing joint structures, accelerating tissue repair, especially at lower doses.

Cinnamaldehyde is a biologically active compound for the disinfection of removable denture: blinded randomized crossover clinical study.

BACKGROUND: Fungal infections associated with the use of dentures, like denture stomatitis, are difficult to prevent and treat. This in situ study aimed to investigate the efficacy of cinnamaldehyde for the disinfection of complete removable dentures, and the effect on the physical and mechanical properties (Vickers microhardness, color, and surface roughness) of the acrylic resin. METHODS: Acrylic resin disks were inserted into the dentures of a probabilistic sample of 33 complete denture users, that used cinnamaldehyde (27 µg/mL) and 0.5% sodium hypochlorite solutions in a 20 min/7-days protocol of dentures immersion in each solution, with a wash-out period of 7 days, to constitute a crossover-study. The disks were analyzed before and after the immersion, for the presence of microorganisms (CFU/mL) and by scanning electron microscope (SEM). Also, the surface roughness (Ra) and Vickers microhardness were measured, and color parameters were analyzed using the National Bureau of Standards (NBS) method. Data was analyzed by Wilcoxon and Friedman (microbiological evaluation), paired t-test (color and roughness) and independent t-test (Vickers hardness) (α = 0.05). RESULTS: A significant reduction (P < 0.05) in the number of microorganisms was observed for each species (total microorganisms, Streptococcus mutans, and Candida spp.), with no significant differences (P > 0.05) between hypochlorite and cinnamaldehyde. There was an increase in the roughness and a decrease in the hardness of the test specimens, with no difference between the two disinfectant substances (P > 0.05). Both hypochlorite and cinnamaldehyde also caused changes in color, considered as "perceptible" by the NBS classification, but with no significant difference between disinfectant substances (P < 0.05), and under the clinically acceptable limit (ΔE ≤ 3.7). CONCLUSION: The 27 µg/mL cinnamaldehyde solution was effective against all evaluated microorganisms and caused minor alterations in hardness, surface roughness, and color parameters, with no clinical relevance.

Application of platelet-rich plasma in the in vitro production of bovine embryos.

The aim of this study was to replace fetal bovine serum (FBS) with platelet-rich plasma (PRP) for in vitro production of bovine embryos. The maturation media (TCM-199 medium) for the cumulus-oocyte complexes (COCs) was supplemented with 5% (G5) and 10% (G10) PRP or 10% FBS (GC). After fertilization, the presumed zygotes were randomly distributed in culture medium supplemented with 5% (G5) and 10% (G10) PRP or 10% FBS (GC) for 7 days. Cumulus cell (CC) expansion was greater (P < 0.05) in the GC (88.9%) group than in G5 (34.1%) or G10 (50.0%). Nevertheless, the expansion of CCs in group G10 was greater than in G5 (P < 0.05). Cleavage was higher in group G5 (86.0%) than in G10 (79.0%) (P < 0.05) and did not differ from group GC (82.0%). The percentage of blastocysts in group G5 (50.0%) was higher than in CG (40.2%) and G10 (34.2%) (P < 0.05). In addition, the number of blastomeres was higher in G5 (159.0 ± 4.18) than in GC (132.4 ± 4.11) and in G10 (127.1 ± 5.88) (P < 0.05). The addition of PRP into the oocytes maturation medium is not beneficial. On the other hand, the PRP addition into the embryo culture medium at 5% concentration is recommended where it increased the quantity and quality of in vitro-produced bovine embryos.

The diabetes drug liraglutide reverses cognitive impairment in mice and attenuates insulin receptor and synaptic pathology in a non-human primate model of Alzheimer's disease.

Alzheimer's disease (AD) is a devastating neurological disorder that still lacks an effective treatment, and this has stimulated an intense pursuit of disease-modifying therapeutics. Given the increasingly recognized link between AD and defective brain insulin signaling, we investigated the actions of liraglutide, a glucagon-like peptide-1 (GLP-1) analog marketed for treatment of type 2 diabetes, in experimental models of AD. Insulin receptor pathology is an important feature of AD brains that impairs the neuroprotective actions of central insulin signaling. Here, we show that liraglutide prevented the loss of brain insulin receptors and synapses, and reversed memory impairment induced by AD-linked amyloid-ß oligomers (AßOs) in mice. Using hippocampal neuronal cultures, we determined that the mechanism of neuroprotection by liraglutide involves activation of the PKA signaling pathway. Infusion of AßOs into the lateral cerebral ventricle of non-human primates (NHPs) led to marked loss of insulin receptors and synapses in brain regions related to memory. Systemic treatment of NHPs with liraglutide provided partial protection, decreasing AD-related insulin receptor, synaptic, and tau pathology in specific brain regions. Synapse damage and elimination are amongst the earliest known pathological changes and the best correlates of memory impairment in AD. The results illuminate mechanisms of neuroprotection by liraglutide, and indicate that GLP-1 receptor activation may be harnessed to protect brain insulin receptors and synapses in AD. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Antifungal activity and Shore A hardness of a tissue conditioner incorporated with terpinen-4-ol and cinnamaldehyde.

PURPOSE: This study investigated the anti-Candida activity and the Shore A hardness of a tissue conditioner (Softone™) modified by incorporation of terpinen-4-ol and cinnamaldehyde. MATERIAL AND METHODS: Agar diffusion, microdilution, and mechanism of action methods were performed to determine to evaluate the antifungal activity of phytoconstituents. Then, phytoconstituents in varying concentrations were incorporated into the tissue conditioner. The anti-Candida effect of the modified conditioner was evaluated through agar punch well and biofilm formation methods. Shore A hardness of the experimental liners was evaluated after baseline, 24 h, 48 h, 4 days, and 7 days immersion on artificial saliva. RESULTS: The phytoconstituents incorporated into Softone showed completely inhibited fungal growth in concentrations of 20-40% and did not present significant antifungal activity until their concentrations where higher than 5%. There were differences between non-modified Softone and M5, M10, C10, and T10% (p < 0.05). The groups containing 10-40% of cinnamaldehyde incorporated into Softone were able to completely inhibit the biofilm. Concentrations below 40% of terpinen-4-ol showed unsatisfactory biofilm inhibition. The T40% and C40% groups presented the lowest Shore A hardness values. Hardness values from groups T40% at 7 days (p = 0.476); C40% at 4 days (p = 0.058); and T20% (p = 0.058), C20% (p = 0.205), T30% (p = 0.154), and C30% (p = 0.874) after 48 h did not differ from the control group. CONCLUSIONS: Cinnamaldehyde incorporated into Softone inhibited Candida biofilm formation at concentrations of 10-40%, being more effective than terpinen-4-ol modification despite of halo inhibition observed by both products. CLINICAL RELEVANCE: All modifications showed a very similar pattern of hardness being useful for clinical practice.