Factors associated with mortality of elderly people due to COVID-19: Protocol for systematic review and meta-analysis.

INTRODUCTION: The COVID-19 pandemic has become a significant health crisis, marked by high mortality rates on a global scale, with mortality from the disease being notably concentrated among the elderly due to various factors. OBJECTIVE: This study aims to investigate the biological and non-biological factors associated with COVID-19 mortality rates among the elderly worldwide. METHODS: The following databases will be consulted: PubMed, Scopus, EMBASE, Web of Science and ScienceDirect. Longitudinal observational studies (cohort and case-control-risk factors) will be included. The risk of bias, defined as low, moderate, high, will be assessed using the National Heart, Lung and Blood Institute (NHLBI) Quality Assessment Tool for observational cohort and cross-sectional studies. Two independent authors will conduct the searches, and any possible disagreements will be resolved by a third author. Heterogeneity between study results will be assessed using a standard X2 test with a significance level of 0.05, and an I2 value will be calculated to further assess heterogeneity. The random effects model for meta-analyses will be adopted to distribute the weight between the studies and standardize their contributions. The meta-analyses will be conducted using RevMan software. DISCUSSION: Despite the numerous publications on COVID-19 mortality among the elderly, there is still a gap in knowledge, as there is no systematic review and meta-analysis that summarizes the main biological and non-biological associated factors globally. CONCLUSION: The results of this study will consolidate the latest evidence and address gaps in the overall understanding of biological or non-biological associated factors. This knowledge will facilitate the development of appropriate health strategies for this demographic group and pave the way for further research. TRIAL REGISTRATION: PROSPERO (CRD42023400873).

The effects of re-irradiation on the chemical and morphological properties of permanent teeth.

This study aimed to assess the in vitro effects of re-irradiation on enamel and dentin properties, simulating head and neck cancer radiotherapy retreatment. Forty-five human permanent molars were classified into five groups: non-irradiated; irradiated 60 Gy, and re-irradiated with doses of 30, 40, and 50 Gy. Raman spectroscopy, scanning electron microscopy (SEM), and energy dispersive x-ray spectroscopy (EDS) were employed for analysis. Raman spectroscopy assessed intensity, spectral area, and specific peaks comparatively. Statistical analysis involved Kolmogorov-Smirnov and One-Way ANOVA tests, with Tukey's post-test (significance level set at 5%). Significant changes in irradiated, non-irradiated, and re-irradiated enamel peaks were observed, including phosphate (438 nm), hydroxyapatite (582 nm), phosphate (960 nm), and carbonate (1070 nm) (p < 0.05). Re-irradiation affected the entire tooth (p > 0.05), leading to interprismatic region degradation, enamel prism destruction, and hydroxyapatite crystal damage. Dentin exhibited tubule obliteration, crack formation, and progressive collagen fiber fragmentation. EDX revealed increased oxygen percentage and decreased phosphorus and calcium post-reirradiation. It is concluded that chemical and morphological changes in irradiated permanent teeth were dose-dependent, exacerbated by re-irradiation, causing substantial damage in enamel and dentin.

Brazilian National Network of Alternative Methods (RENAMA) 10th Anniversary: Meeting of the Associated Laboratories, May 2022.

The Brazilian National Network of Alternative Methods (RENAMA), which is linked to the Ministry of Science, Technology and Innovation, is currently comprised of 51 laboratories from CROs, academia, industry and government. RENAMA's aim is to develop and validate new approach methodologies (NAMs), as well as train researchers and disseminate information on their use - thus reducing Brazilian, and consequently Latin American, dependence on external technology. Moreover, it promotes the adoption of NAMs by educators and trained researchers, as well as the implementation of good laboratory practice (GLP) and the use of certified products. The RENAMA network started its activities in 2012, and was originally comprised of three central laboratories - the National Institute of Metrology, Quality and Technology (INMETRO); the National Institute of Quality Control in Health (INCQS); and the National Brazilian Biosciences Laboratory (LNBio) - and ten associated laboratories. In 2022, RENAMA celebrated its 10th anniversary, a milestone commemorated by the organisation of a meeting attended by different stakeholders, including the RENAMA-associated laboratories, academia, non-governmental organisations and industry. Ninety-six participants attended the meeting, held on 26 May 2022 in Balneário Camboriú, SC, Brazil, as part of the programme of the XXIII Brazilian Congress of Toxicology 2022. Significant moments of the RENAMA were remembered, and new goals and discussion themes were established. The lectures highlighted recent innovations in the toxicological sciences that have translated into the assessment of consumer product safety through the use of human-relevant NAMs instead of the use of existing animal-based approaches. The challenges and opportunities in accepting such practices for regulatory purposes were also presented and discussed.

A network-based approach to understanding gene-biological processes affecting economically important traits of Nelore cattle.

This study aimed to build gene-biological process networks with differentially expressed genes associated with economically important traits of Nelore cattle from 17 previous studies. The genes were clustered into three groups by evaluated traits: group 1, production traits; group 2, carcass traits; and group 3, meat quality traits. For each group, a gene-biological process network analysis was performed with the differentially expressed genes in common. For production traits, 37 genes were found in common, of which 13 genes were enriched for six Gene Ontology (GO) terms; these terms were not functionally grouped. However, the enriched GO terms were related to homeostasis, the development of muscles and the immune system. For carcass traits, four genes were found in common. Thus, it was not possible to functionally group these genes into a network. For meat quality traits, the analysis revealed 222 genes in common. CSRP3 was the only gene differentially expressed in all three groups. Non-redundant biological terms for clusters of genes were functionally grouped networks, reflecting the cross-talk between all biological processes and genes involved. Many biological processes and pathways related to muscles, the immune system and lipid metabolism were enriched, such as striated muscle cell development and triglyceride metabolic processes. This study provides insights into the genetic mechanisms of production, carcass and meat quality traits of Nelore cattle. This information is fundamental for a better understanding of the complex traits and could help in planning strategies for the production and selection systems of Nelore cattle.

Gamification as a health education strategy of adolescents at school: Protocol for a systematic review and meta-analysis.

The objective of the study is to present a systematic review and meta-analysis protocol for evaluating the effects of health education gamification-based interventions, on health parameters (food consumption, sleep quality and physical activity) of adolescent students. This protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42022373833). The search will be performed in the following databases: MEDLINE, Embase, Scopus, ERIC, ScienceDirect, Web of Science, Cochrane, LILACS, APA, and ADOLEC. Intervention studies (clinical trials - randomized or non-randomized) and quasi-experimental studies will be included. The risk of bias will be assessed using the Risk of Bias in Non-randomized Studies of Interventions tool for randomized controlled trials, non- randomized controlled trials and quasi-experimental trials. Two independent researchers will conduct all assessments, and any disagreements will be consulted with a third reviewer. Data analysis and synthesis will be analyzed using RevMan 5.4.1 software. We will conduct the study in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guideline. The review will summarize the current evidence on gamification health education changes in parameters related to the health of adolescents. Gamification has been used to verify the increase in adherence to healthy habits or the development of health-related skills, but there are still few results for the adolescent population. We expect that the systematic review could indicate strategies with gamification interventions and also determine how these strategies can improve health parameters of adolescent students, and they will be available as a reference for these interventions.

Hypercitratemia is a mortality predictor among patients on continuous venovenous hemodiafiltration and regional citrate anticoagulation.

The use of regional citrate anticoagulation (RCA) in liver failure (LF) patients can lead to citrate accumulation. We aimed to evaluate serum levels of citrate and correlate them with liver function markers and with the Cat/Cai in patients under intensive care and undergoing continuous venovenous hemodiafiltration with regional citrate anticoagulation (CVVHDF-RCA). A prospective cohort study in an intensive care unit was conducted. We compared survival, clinical, laboratorial and dialysis data between patients with and without LF. Citrate was measured daily. We evaluated 200 patients, 62 (31%) with LF. Citrate was significantly higher in the LF group. Dialysis dose, filter lifespan, systemic ionized calcium and Cat/Cai were similar between groups. There were weak to moderate positive correlations between Citrate and indicators of liver function and Cat/Cai. The LF group had higher mortality (70.5% vs. 51.8%, p = 0.014). Citrate was an independent risk factor for death, OR 11.3 (95% CI 2.74-46.8). In conclusion, hypercitratemia was an independent risk factor for death in individuals undergoing CVVHDF-ARC. The increase in citrate was limited in the LF group, without clinical significance. The correlation between citrate and liver function indicators was weak to moderate.

A code for clinical trials centralized monitoring, sharing open-science solutions to high-quality data.

Monitoring of clinical trials is critical to the protection of human subjects and the conduct of high-quality research. Even though the adoption of risk-based monitoring (RBM) has been suggested for many years, the RBM approach has been less widespread than expected. Centralized monitoring is one of the RMB pillars, together with remote-site monitoring visits, reduced Source Data Verification (SDV) and Source Document Reviews (SDR). The COVID-19 pandemic promoted disruptions in the conduction of clinical trials, as on-site monitoring visits were adjourned. In this context, the transition to RBM by all actors involved in clinical trials has been encouraged. In order to ensure the highest quality of data within a COVID-19 clinical trial, a centralized monitoring tool alongside Case Report Forms (CRFs) and synchronous automated routines were developed at the clinical research platform, Fiocruz, Brazilian Ministry of Health. This paper describes how these tools were developed, their features, advantages, and limitations. The software codes, and the CRFs are available at the Fiocruz Data Repository for Research-Arca Dados, reaffirming Fiocruz's commitment to Open Science practices.

Extended reality as a health education strategy of adolescents at school: protocol for systematic review and meta-analysis.

INTRODUCTION: Extended reality (XR) is the ensemble of interactive experiences based on a computer-simulated environment that encompasses virtual reality and augmented reality and has been proven to be potentially innovative in the field of health education with adolescents. The objective of this study is to present a systematic review and meta-analysis protocol that seeks to evaluate the main effects of interventions that use XR on health parameters (food intake, sound quality and physical activity) of adolescent students. METHODS AND ANALYSIS: The literature search will be performed in the following databases: MEDLINE, Embase, Scopus, ERIC, ScienceDirect, Web of Science, Cochrane, LILACS, APA and ADOLEC. Intervention studies (clinical trials-randomised or non-randomised) and quasi-experimental studies will be included. The risk of bias will be assessed using the Risk of Bias in Non-randomized Studies of Interventions tool for randomised controlled trials (RCTs), non-RCTs and quasi-experimental trials. Two independent researchers will conduct all the assessments, and any disagreements will be consulted with a third reviewer. Data analysis and synthesis will be performed using RevMan V.5.4.1 software. The study will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guideline. ETHICS AND DISSEMINATION: Ethical approval and human consent were not required, as this is a protocol for a systematic review and only secondary data will be used. The findings will be published in a journal and presented at conferences. In case of any changes to this protocol, it will be updated in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses website, and the modifications will be explained in the final report of this review. PROSPERO REGISTRATION NUMBER: CRD42022373876.

Potential outbreak by herpesvirus in equines: detection, clinical, and genetic analysis of equid gammaherpesvirus 2 (EHV-2).

BACKGROUND: Equid herpesvirus (EHV) commonly affects horses causing neurologic and respiratory symptoms beside spontaneous abortions, meaning huge economic losses for equine industry worldwide. In foals, the virus can facilitate secondary infections by Rhodococcus equi, important in morbidity and mortality in equines. A total of five genotypes of EHV were previously described in Brazil including EHV-1, EHV-2, EHV-3, EHV-4, and EHV-5. EHV-2 genotype had only been previously described in Brazil in asymptomatic animals. We report the investigation of the dead of 11 foals in Middle-west region of Brazil showing respiratory and neurological symptoms, as well as several abortions in mares from the same farm. METHODS: Clinical and laboratory exams were performed in this case study. Lung, whole blood, serum, and plasma samples were analyzed by necroscopic and histopathologic techniques followed by molecular assays (conventional and qPCR and Sanger sequencing). RESULTS AND CONCLUSION: Laboratory exams revealed neutrophilia leukocytosis. Necroscopic and histopathologic findings were suppurative bronchopneumonia and ulcerative enteritis. Molecular assays point to the absence of the bacteria Rhodococcus equi and other viruses (including other EHV). The presence of EHV-2 DNA was confirmed by sequencing in serum sample from one foal. This is the first confirmed outbreak of EHV-2 causing disease in Brazilian horses with confirmed presence of the virus, and which highlight the important role of EHV-2 in equine respiratory disease and spontaneous abortions in equid in Brazil.

Laparoscopic nephron-sparing surgery for the treatment of canine dioctophymosis.

This paper reports on two cases of laparoscopic nephrotomy employed in the treatment of canine dioctophymosis, which is considered a unusual procedure and a new treatment proposal heretofore not performed in veterinary medicine. Two patients were treated, one with a history of hematuria and the other with incidental finding of the parasite in the abdominal cavity during elective ovariohysterectomy. Both dogs were subjected to abdominal ultrasound, which produced images indicating the presence of the parasite in the right side kidney, but with partial parenchymal preservation. The patients were therefore subjected to laparoscopic nephrotomy. The surgical procedure was effective in treating dioctophymosis and enabled minimum tissue invasion during surgery, in addition to preservation of the kidney.

Tick infestation level interferes with spray formulation (organophosphate + pyrethroid) efficacy against Rhipicephalus microplus.

Due to the scarcity of information regarding the control of Rhipicephalus microplus on bovines with different tick burdens, tick counts and the efficacy of a commercial spray formulation (aspersion bath with organophosphate + pyrethroid) were evaluated for animals with a low and high tick burdens for 35 days in a stall test. Thirty-two crossbreed Bos taurus indicus x Bos t. taurus experimentally infested with R. microplus larvae were divided into four groups: T01 high infestation control, T02 high infestation treated, T03 low infestation control, and T04 low infestation treated. The bovines were kept individually in pens and R. microplus females were collected daily. All data were statistically analyzed with a significance level of 5% (P ≤ 0.05). For linear regressions, variables with P≤0.05 and the highest coefficients of determination (R2 ≥ 0.70) were considered the best descriptors. The reliability level was 95%. Tick counts differed (P<0.0001) between T01 and T02 (high infestation control vs. treated), except at day 2 (P >0.05) post-treatment, and efficacy ranged from 85.2 to 50.6%. The number of collected engorged females was lower (P<0.0001) for T04 than for T03 (low infestation treated vs. control) animals from day 3 to 29, and efficacy ranged from 95.2 to 69.8%. In addition, tick burden and efficacy were negatively correlated for both the group of animals with a high tick burden (r = -0.5256; p = 0.0012; R² = 0.2762) and the group of animals with a low tick burden (r = -0.9817; p < 0.0001; R² = 0.9638). In conclusion, a high tick burden on bovines decreases the efficacy of the tested spray acaricide.

Shade availability on pasture does not affect semen characteristics of Brahman bulls (Bos taurus indicus).

Testicular degeneration by heat is the leading cause of infertility in bulls. Beef cattle are generally farmed under hot and humid conditions, and consequently, the thermotolerance of each breed must be considered in their natural environment. This study aimed to evaluate the reproductive characteristics of Brahman bulls maintained in the grazing system, with or without shadow availability. Ten Brahman bulls aging between 24 and 30 months were allocated in two different paddocks, with or without shadow availability. The heat tolerance test was performed on three non-consecutive typical summer days. The semen samples were collected at four times points in a 14 days interval. The climate conditions were monitored throughout the experiment; and clinical evaluation, testicular consistence and scrotal circumference were measured before every semen collection. In addition, semen was evaluated regarding volume, aspect, turbulence, motility, straight movement, sperm concentration, and morphological exam. The studied Brahman bulls showed a high thermolysis capacity, high heat tolerance, and no differences in semen quality were observed between groups.

A degeneração testicular causada pelo calor é a principal causa de infertilidade em touros. Bovinos de corte geralmente são criados em condições de calor e umidade, e, consequentemente, a termotolerância de cada raça deve ser considerada em seu ambiente natural. O presente trabalho teve como objetivo avaliar as características reprodutivas de touros da raça Brahman mantidos em sistema de pastejo, com ou sem disponibilidade de sombra. Dez touros Brahman com idades entre 24 e 30 meses foram alocados em dois piquetes diferentes, com ou sem disponibilidade de sombra. O teste de tolerância ao calor foi realizado em três dias típicos de verão não consecutivos. As amostras de sêmen foram coletadas em quatro momentos em intervalos de 14 dias. As condições climáticas foram monitoradas durante todo o período experimental; e a avaliação clínica, consistência testicular e a circunferência escrotal foram avaliadas antes de cada coleta de sêmen. Ainda, o sêmen foi avaliado quanto ao volume, aspecto, turbulência, motilidade, vigor, concentração espermática e exame morfológico. Os touros estudados da raça Brahman apresentaram alta capacidade de termólise, alta tolerância ao calor, e não foram observadas diferenças na qualidade do sêmen entre os grupos.

Transcutaneous tibial nerve stimulation to treat urgency urinary incontinence in older women: 12-month follow-up of a randomized controlled trial.

INTRODUCTION AND HYPOTHESIS: Urgency urinary incontinence (UUI) is highly prevalent in elderly individuals and has a great impact on quality of life. Transcutaneous tibial nerve stimulation (TTNS) can be an effective treatment option for UUI in older women. METHODS: This is a single-center randomized clinical trial with a 12-month follow-up involving 106 women > 60 years of age. Kegel exercises and bladder retraining were performed alone or in combination with TTNS, which consisted of using a transcutaneous electrical nerve stimulator for 30 min once a week for 12 weeks with the following settings: continuous mode, 10 Hz, 200 ms, and 10 to 50 mA (according to hallux mobilization). Responders to therapy who experienced failure during follow-up were invited for a 3-week protocol with the same parameters as those used for the initial therapy. Patients were evaluated at baseline, 4 weeks after the 12-week protocol, and every 3 months for 12 months, through subjective satisfaction questionnaires, a 3-day bladder diary and the International Consultation on Incontinence Questionnaire-Short Form. King's Health Questionnaire was applied pretreatment and 4 weeks after the last session of the 12-week protocol. RESULTS: A total of 101 women completed the initial 12-week protocol. TTNS patients reported 66.7% subjective global satisfaction vs. 32.0% in the control group (p < 0.001). The TTNS group showed statistically significant improvement in quality of life (QoL) and UUI parameters compared with the control group. Forty-eight patients were satisfied after the 12-week protocol and completed the 12-month follow-up (32 in the TTNS group and 16 in the control group). A total of 80.5% of responders to TTNS were still satisfied at the end of the 12-month follow-up vs. 30.8% in the control group (p = 0.009). CONCLUSION: TTNS is effective at the 12-month follow-up for the treatment of UUI in elderly women.

Logistic Regression Model in a Machine Learning Application to Predict Elderly Kidney Transplant Recipients with Worse Renal Function One Year after Kidney Transplant: Elderly KTbot.

BACKGROUND: Renal replacement therapy (RRT) is a public health problem worldwide. Kidney transplantation (KT) is the best treatment for elderly patients' longevity and quality of life. OBJECTIVES: The primary endpoint was to compare elderly versus younger KT recipients by analyzing the risk covariables involved in worsening renal function, proteinuria, graft loss, and death one year after KT. The secondary endpoint was to create a robot based on logistic regression capable of predicting the likelihood that elderly recipients will develop worse renal function one year after KT. METHOD: Unicentric retrospective analysis of a cohort was performed with individuals aged ≥60 and <60 years old. We analysed medical records of KT recipients from January to December 2017, with a follow-up time of one year after KT. We used multivariable logistic regression to estimate odds ratios for elderly vs younger recipients, controlled for demographic, clinical, laboratory, data pre- and post-KT, and death. RESULTS: 18 elderly and 100 younger KT recipients were included. Pretransplant immune variables were similar between two groups. No significant differences (P > 0.05) between groups were observed after KT on laboratory data means and for the prevalences of diabetes mellitus, hypertension, acute rejection, cytomegalovirus, polyomavirus, and urinary infections. One year after KT, the creatinine clearance was higher (P = 0.006) in youngers (70.9 ± 25.2 mL/min/1.73 m2) versus elderlies (53.3 ± 21.1 mL/min/1.73 m2). There was no difference in death outcome comparison. Multivariable analysis among covariables predisposing chronic kidney disease epidemiology collaboration (CKD-EPI) equation <60 mL/min/1.73 m2 presented a statistical significance for age ≥60 years (P = 0.01) and reduction in serum haemoglobin (P = 0.03). The model presented goodness-fit in the evaluation of artificial intelligence metrics (precision: 90%; sensitivity: 71%; and F 1 score: 0.79). CONCLUSION: Renal function in elderly KT recipients was lower than in younger KT recipients. However, patients aged ≥60 years maintained enough renal function to remain off dialysis. Moreover, a learning machine application built a robot (Elderly KTbot) to predict in the elderly populations the likelihood of worse renal function one year after KT.

Assessing Agricultural Toxicity in Brazil: Advances and Opportunities in the 21st Century.

Agriculture in the 21st century faces multiple challenges to produce food for the growing population using ethical/sustainable and efficient methods safely for humans and the environment. Brazil today is a world leader in terms of production of food of plant origin, both for human consumption and animal feed. Agriculture and livestock raising are critical economic activities in maintaining a positive balance in its economy. As a consequence, the registration and use of pesticides in Brazil have grown at an accelerated rate. This work shows the current situation in Brazil in terms of the prevailing laws about the registration of pesticides, with a focus on the toxicological aspects related to human health. The regulatory aspects of registration of pesticides in Brazil, the mandatory testing for evaluating pesticide toxicity, adoption of the Globally Harmonized System of Classification and Labeling of Chemicals, and recent progress toward nonanimal methods to toxicity evaluation were explored in this work. In this field, Brazil has advanced and there are opportunities and challenges. There is still much to be done and investments to be made so that Brazil can definitively consolidate its conduct within the context of a Modern Regulatory Toxicology, which has entered the 21st century.

Fabrication and characterization of remineralizing dental composites containing hydroxyapatite nanoparticles.

The aim of this study was to fabricate and characterize dental composites containing hydroxyapatite nanoparticles (HApNPs). Four dental composites were produced from the same organic matrix (70 wt% Bis-GMA and 30 wt% TEGDMA), with partial replacement of BaBSi particles (65 wt%) by HApNPs in the following concentrations (wt%): E0 (0) - control, E10 (10), E20 (20) and E30 (30). Ca2+ and PO43- release was evaluated in solutions with different pHs (4, 5.5, and 7) using atomic emission spectroscopy with microwave-induced nitrogen plasma while the enamel remineralization potential was evaluated in caries-like enamel lesions induced by S. mutans biofilm using micro-CT. The following properties were characterized: degree of conversion (DC%), microhardness (KHN), flexural strength (FS), elastic modulus (EM) and translucency (TP). The higher the HApNPs content, the higher the Ca2+ and PO43- release. The ions release was influenced by pH (4 > 5.5 > 7) (p < 0.05). All composites loaded with HApNPs were able to remineralize the enamel (E30 = E20 > E10) (p < 0.05). Contrarily, E0 was not able of recovering the enamel mineral loss. E0 and E10 presented highest DC%, while E20 and E30 showed similar and lowest DC%. KHN and FS were decreased with the addition of HApNPs, while EM was not influenced by the incorporation of HApNPs. E10 presented statistically similar TP to E0, while this property decreased for E20 and E30 (p < 0.05). Incorporation of HApNPs into dental composites promoted enamel remineralization, mainly at potentially cariogenic pH (= 4), while maintained their overall performance in terms of physicomechanical properties.

Design, synthesis and pharmacological assessment of new pyrazole compounds.

AIMS: This study investigated the antinociceptive and anti-inflammatory effects of new pyrazole compounds LQFM011(5), LQFM043(6) and LQFM044(7) as well as the mechanisms of action and acute in vitro toxicity. MAIN METHODS: The antinociceptive activity was evaluated using the acetic acid-induced abdominal writhing test, formalin-induced pain test and the Randall-Selitto test. The anti-inflammatory activity was evaluated using models of paw oedema and pleurisy induced by carrageenan; cell migration, the levels of tumour necrosis factor α (TNF-α) and myeloperoxidase (MPO) enzyme activity were evaluated. In addition, the ability to inhibit phospholipase A2 (PLA2) in vitro and docking in PLA2 were used. Acute oral systemic toxicity in mice was evaluated through the neutral red uptake assay. KEY FINDINGS: The synthesised compounds (5-7), delivered via gavage (p.o.) at 70, 140 or 280 µmol/kg, decreased the number of writhings induced by acetic acid; the three compounds (280 µmol/kg p.o.) reduced the paw licking time in the first and second phase of the formalin test and decreased the nociceptive threshold variation in the Randall-Selitto test. Furthermore, this dose reduced oedema formation, leucocyte migration (specifically through reduction in polymorphonuclear cell movement) and increased mononuclear cells. MPO activity and the levels of pro-inflammatory cytokines TNF-α were decreased. Evaluation of PLA2 inhibition via the docking simulation revealed more interactions of LQFM043R(6) and LQFM044(7), data that corroborated the half-maximal inhibitory concentration (IC50) of PLA2 inhibition in vitro. Therefore, LQFM011(5), LQFM043(6) and LQFM044(7) were classified with the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) as category 4.

Characterization and effect of nanocomplexed fluoride solutions on the inhibition of enamel demineralization created by a multispecies cariogenic biofilm model.

OBJECTIVES: The aim of this study was to assess the in vitro caries preventive effect of nanocomplexed solutions of hydroxypropyl-ß-cyclodextrin and γ-cyclodextrin associated with titanium tetrafluoride (TiF4) after different complexation times (12 or 72 h). MATERIALS AND METHODS: Enamel blocks were randomly distributed in 9 groups (n = 11): negative control, hydroxypropyl-ß-cyclodextrin, γ-cyclodextrin, TiF4, hydroxypropyl-ß-cyclodextrin:TiF4 12 h, hydroxypropyl-ß-cyclodextrin:TiF4 72 h, γ-cyclodextrin:TiF4 12 h, γ-cyclodextrin:TiF4 72 h, and NaF (positive control). The solutions were applied for 1 min and the blocks were exposed to a biofilm model. Nanocompounds were characterized by differential scanning calorimetry and X-ray powder diffraction. The percentage of surface microhardness loss (%SML), mineral density changes (ΔZ), lesion depth, surface morphology (scanning electron microscopy-SEM), and chemical characterization (energy-dispersive spectroscopy-EDS) were assessed. RESULTS: No oxidation was observed, and the formation of the nanocomplexes was evidenced by changes in the melting point compared to pure cyclodextrins and the loss of crystallinity of the materials. Hydroxypropyl-ß-cyclodextrin:TiF4 72 h resulted in lower %SML than negative control, hydroxypropyl-ß-cyclodextrin, γ-cyclodextrin, and TiF4 (p < 0.05). NaF differed from all groups (p < 0.05), except for hydroxypropyl-ß-cyclodextrin:TiF4 72 h (p = 0.83). ΔZ of hydroxypropyl-ß-cyclodextrin:TiF4 72 h was higher than negative control, hydroxypropyl-ß-cyclodextrin, γ-cyclodextrin, γ-cyclodextrin:TiF4 1 2 h, γ-cyclodextrin:TiF4 72 h, and NaF (p < 0.05) and similar to TiF4 and hydroxypropyl-ß-cyclodextrin:TiF4 12 h (p > 0.05). SEM/EDS detected Ti in the blocks subjected to TiF4-products. CONCLUSION: The hydroxypropyl-ß-cyclodextrin:TiF4 72 h solution showed caries preventive effect on the surface and subsurface of the enamel. CLINICAL RELEVANCE: A hydroxypropyl-ß-cyclodextrin nanosystem, in association with TiF4 after 72 h of complexation, may be a promising agent for the prevention of enamel demineralization.