Metabolic Fingerprinting Links Oncogenic PIK3CA with Enhanced Arachidonic Acid-Derived Eicosanoids.

Oncogenic transformation is associated with profound changes in cellular metabolism, but whether tracking these can improve disease stratification or influence therapy decision-making is largely unknown. Using the iKnife to sample the aerosol of cauterized specimens, we demonstrate a new mode of real-time diagnosis, coupling metabolic phenotype to mutant PIK3CA genotype. Oncogenic PIK3CA results in an increase in arachidonic acid and a concomitant overproduction of eicosanoids, acting to promote cell proliferation beyond a cell-autonomous manner. Mechanistically, mutant PIK3CA drives a multimodal signaling network involving mTORC2-PKCζ-mediated activation of the calcium-dependent phospholipase A2 (cPLA2). Notably, inhibiting cPLA2 synergizes with fatty acid-free diet to restore immunogenicity and selectively reduce mutant PIK3CA-induced tumorigenicity. Besides highlighting the potential for metabolic phenotyping in stratified medicine, this study reveals an important role for activated PI3K signaling in regulating arachidonic acid metabolism, uncovering a targetable metabolic vulnerability that largely depends on dietary fat restriction. VIDEO ABSTRACT.

A multicentre study of amphotericin B treatment for histoplasmosis: assessing mortality rates and adverse events.

BACKGROUND: Progressive disseminated histoplasmosis is a significant issue in Latin America, particularly in Brazil, contributing to high mortality rates. OBJECTIVES: Our objectives were to comprehensively describe histoplasmosis treatment with various amphotericin B (AmB) formulations, including mortality rates, adverse effects and risk factors for mortality. METHODS: This multicentre retrospective cohort study (January 2014-December 2019) evaluated medical records of patients with proven or probable histoplasmosis treated with at least two doses of AmB in seven tertiary medical centres in Brazil. We assessed risk factors associated with death during hospitalization using univariate and multivariate analyses. RESULTS: The study included 215 patients, mostly male (n = 158, 73%) with HIV infection (n = 187, 87%), and a median age of 40 years. Only 11 (5%) patients initiated treatment with liposomal amphotericin B (L-AmB). Amphotericin B deoxycholate (D-AmB) was administered to 159 (74%) patients without changes in the treatment. The overall mortality during hospitalization was 23% (50/215). Variables independently associated with mortality were use of D-AmB (OR 4.93) and hospitalization in ICU (OR 9.46). There was a high incidence of anaemia (n = 19, 90%), acute kidney injury (n = 96, 59%), hypokalaemia (n = 73, 55%) and infusion reactions (n = 44, 20%) during treatment. CONCLUSIONS: We found that D-AmB was the main formulation, which was also associated with a higher mortality rate. Lipid formulations of AmB have become more readily available in the public health system in Brazil. Further studies to evaluate the effectiveness of L-AmB will likely show improvements in the treatment outcomes for patients with disseminated histoplasmosis.

Masturbation, sexual function, and genital self-image of undergraduate women: a cross-sectional study.

BACKGROUND: The relationship between factors related to masturbation, sexual function, and genital self-image among women has not been fully explored in the literature. AIM: The study sought to investigate the association between masturbation frequency, feelings, and behaviors with sexual function and genital self-image in young women. METHODS: A cross-sectional survey among 110 undergraduate female students was conducted. Online self-administered questionnaires to assess sociodemographic characteristics, masturbatory frequency, feelings, and behavior were completed. Participants also answered the Brazilian version of the Female Sexual Function Index (FSFI) and the Female Genital Self-Image Scale (FGSIS). OUTCOMES: The outcome includes masturbation frequency and behaviors associated, as well as scores on the FSFI and FGSIS. RESULTS: Women showed higher scores in FSFI subdomains when masturbation was considered important for them, along with reported feelings of empowerment and satisfaction during this activity. However, those who experienced negative emotions during masturbation, such as shame or guilt, demonstrated a significant association with lower scores in both FSFI and FGSIS. Masturbation frequency was found to correlate with better sexual function specifically in the desire domain among women who engaged in daily masturbation. Additionally, an association was observed between higher scores in the FGSIS and increased scores in the domains of satisfaction, arousal, and orgasm within the FSFI. There was an association in the domain's satisfaction, arousal, and orgasm of the FSFI with greater scores in FGSIS. CLINICAL IMPLICATIONS: The clinical implications encompass the augmentation of understanding pertaining to female sexual function. STRENGTHS AND LIMITATIONS: The study provides valuable insights into the sexual behavior of undergraduate female students, and its methodology improves openness in responses, as it provides anonymity given the sensitive nature of the topic studied. Study limitations include the unsuitability of the FSFI questionnaire for sexually inactive women in the past 4 weeks; the participation bias and reporting bias in sexuality searches; and the unknown validity of the investigator-derived questionnaire about masturbation, as it has not been previously validated. CONCLUSION: Masturbation frequency has minimal to no impact on female sexual function, whereas harboring positive feelings toward it and maintaining a positive genital self-image may exert a positive influence on sexual function.

Efficacy of articaine anesthesia with needle-free/Comfort-in method and conventional needle injection in dental patients with irreversible pulpitis: a randomized clinical trial.

OBJECTIVE: To assess the anesthetic efficacy of articaine with the needle-free/Comfort-in™ method compared to the conventional needle method. To assess pain during anesthesia application, onset of anesthesia and patient`s self-reported quality of life-related to oral health after the dental emergency appointment. MATERIALS AND METHODS: This parallel, randomized clinical trial was conducted by a single operator/dentist in the state of Maranhao, northeast of Brazil. Included participants were adult dental patients with one molar (maxillary) or premolar (maxillary or mandibular) tooth diagnosed with symptomatic irreversible pulpitis. The primary outcome was the anesthetic efficacy, measured using a combination of electrical and cold pulp tests (cold + EPT) and the Numerical Rating Scale (NRS). Secondary outcomes were pain during anesthesia application, onset of anesthesia, and patient`s quality-of-life (measured with the OHIP-14). RESULTS: 62 patients were randomized in the anesthesia needle-free group and Comfort-in group (34.26 ± 10.786 × 33.29 ± 8.399 years old, respectively). The group of patients in the Comfort-in group had 71.0% success. Patients from the Comfort-in group reported statistically lower pain during the anesthesia application than patients from the conventional group (2.13 ± 2.172 × 6.03 ± 3.146 NRS scores, respectively) as well as immediately after the anesthetic procedure. Patients self-reported negative impact in quality of life was similar between groups before (p > 0.05) and after (p > 0.05) the dental emergency. CONCLUSIONS: Comfort-in™ had similar efficacy to the conventional needle method. CLINICAL RELEVANCE: This trial showed that it is possible to anesthetize patients with tooth pulpits without using needles to provide comfort mainly to anxious patients.

Single High Dose of Liposomal Amphotericin B in Human Immunodeficiency Virus/AIDS-Related Disseminated Histoplasmosis: A Randomized Trial.

BACKGROUND: Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens. METHODS: Prospective randomized multicenter open-label trial of 1- or 2-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14. RESULTS: A total of 118 subjects were randomized, and median CD4+ counts, and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points, and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for single-dose L-AmB, 69% 2-dose L-AmB, and 74% for control arm (P = .69). Overall survival on D14 was 89.0% (34/38) for single-dose L-AmB, 78.0% (29/37) for 2-dose L-AmB, and 92.1% (35/38) for control arm (P = .82). CONCLUSIONS: One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (>4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access.

Characteristics, mortality, associated variables with death, and therapeutic response among HIV-positive, solid organ transplant (SOT), and non-HIV-positive/non-transplant (NHNT) patients with cryptococcosis: First multicenter cohort study in Brazil.

Cryptococcosis is traditionally associated with immunocompromised patients but is increasingly being identified in those without the human immunodeficiency virus (HIV) or other immunocompetent individuals. We aim to describe the characteristics, mortality, and associated variables with death among hospitalized patients with cryptococcosis in Brazil. This is the first multicenter retrospective cohort study conducted in seven public tertiary Brazilian hospitals. A total of 384 patients were included; the median age was 39 years and 283 (73.7%) were men. In all, 304 HIV-positive were hosts (79.2%), 16 (4.2%) solid organ transplant (SOT), and 64 (16.7%) non-HIV-positive/non-transplant (NHNT). Central nervous system (CNS) cryptococcosis had a significantly higher number across disease categories, with 313 cases (81.5%). A total of 271 (70.6%) patients were discharged and 113 (29.4%) died during hospitalization. In-hospital mortality among HIV-positive, SOT, and NHNT was 30.3% (92/304), 12.5% (2/16), and 29.7% (19/64), respectively. Induction therapy with conventional amphotericin B (AMB) mainly in combination with fluconazole (234; 84.2%) was the most used. Only 80 (22.3%) patients received an AMB lipid formulation: liposomal (n = 35) and lipid complex (n = 45). Most patients who died belong to the CNS cryptococcosis category (83/113; 73.4%) when compared with the others (P = .017). Multivariate analysis showed that age and disseminated cryptococcosis had a higher risk of death (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.05; P = .008 and OR, 1.84; 95% CI, 1.01-3.53; P = .048, respectively). Understanding the epidemiology of cryptococcosis in our settings will help to recognize the burden and causes of mortality and identify strategies to improve this scenario.

This multicenter cohort study included 384 hospitalized individuals with cryptococcosis in Brazil. Most individuals were men (74%), HIV-positive (79%), had central nervous system involvement (82%), and received conventional amphotericin plus fluconazole (84%). In-hospital mortality was high (29%).

Thermographic examination of gingival phenotypes: correlation between morphological and thermal parameters.

OBJECTIVES: To evaluate the clinical and thermographic aspects of the gingival phenotype (GP) in healthy subjects. MATERIALS AND METHODS: The study sample examined 264 teeth, upper and lower incisors, comprising 132 central incisors (CI) and 132 lateral incisors (LI), in 33 healthy volunteers. Four periodontal parameters were recorded systematically: ratio of width to length of the dental crown (CW/CL), height of the gingival attachment (KGW), probing depth (PD), and gingival transparency (GT). The temperatures of the attached gingiva (KGW temp) and the free gingival margin (FGM Temp) were also recorded by way of infrared thermography (IRT). RESULTS: The average age of the sample was 30.70 ± 7.65 years. Of the 264 teeth evaluated, 76.1% had a thin GP. There was a significant association between CW/CL (p < 0.001), KGW (p < 0.001), PD (p < 0.007), and FGM Temp (p < 0.006) with the tooth groups. The results show a significant and inversely proportional correlation between clinical parameters and gingival temperature (p < 0.05). A significant association was found between CW/CL (p < 0.026); KGW (p < 0.001); and GP. CONCLUSION: CW/CL, KGW, PD, and FGM Temp vary according to tooth group. The majority of the sample presented with the thin GP, which was more prevalent in the lower LIs and CIs. No significant association could be observed between thermographic parameters and GP. CLINICAL RELEVANCE: Knowledge of the temperature of the gingival tissues can be useful in helping to diagnose and plan periodontal treatments. Moreover, our findings will help future studies evaluate the use of IR as an auxiliary diagnostic method in dentistry, eliminating GP as a confounding factor, since it does not seem to influence the temperature of the gingival tissues.

How is the quality of the available evidence on molar-incisor hypomineralization treatment? An overview of systematic reviews.

OBJECTIVE: This overview analyzed the quality of the systematic reviews (SRs) available on treatments for molar-incisor hypomineralization (MIH). MATERIAL AND METHODS: Six electronic databases were searched (PubMed/MEDLINE, Scopus, Web of Science, LILACS, Brazilian Bibliography of Dentistry and Cochrane Library) until March 2022. Two reviewers independently performed the selection, the quality assessment (Assessment of Multiple Systematic Reviews 2 - AMSTAR-2), and the risk of bias assessment of the SR (Risk of Bias in Systematic Reviews - ROBIS). RESULTS: Two hundred nine records were retrieved; after removing duplicates and applying the inclusion/exclusion criteria, 5 SRs remained. Three SRs were rated as showing critically low methodological quality and high risk of bias, and two were rated as moderate methodological quality and low risk of bias. The identified treatments that may be suitable for MIH were classified as (1) non-invasive - casein incorporated into toothpaste and sugar-free chewing gum, toothpaste containing arginine, 0.4% stannous fluoride gel; fluoride varnish; (2) micro-invasive - resin sealants for pits and fissures, microabrasion, dental whitening, resin infiltration; (3) invasive - ART restorations, indirect restorations (metal, composite, or ceramic); and (4) mixed intervention - stainless steel crowns. CONCLUSION: Despite the considerable number of published papers included in this set of systematic reviews, the evidence supporting the effectiveness of treatments for treating MIH is limited due to the methodological quality and risk of bias of the systematic reviews, as well as the quality of the primary studies (PROSPERO: CRD42020144831). CLINICAL RELEVANCE: Different treatments have been purposed for MIH treatment, but there is still not enough scientific evidence of good quality for the establishment of a definitive clinical protocol for the treatment of MIH.

Experimental pastes containing niobophosphate and 45S5 bioactive glasses for treatment of dentin hypersensitivity: dentin permeability and tubule obliteration.

OBJECTIVES: This study tested the ability of bioactive pastes containing niobophosphate and 45S5 glasses to reduce dentin permeability and to obliterate dentinal tubules, as a mean of reducing human dentin hypersensitivity. MATERIALS AND METHODS: Experimental pastes with concentrations of 10, 20, and 30 wt% of two bioactive glasses (45S5 or niobophosphate [NbG]) were formulated. A paste without bioactive glass (placebo) and a commercial paste (Nano P, FGM) were used as controls. Forty dentin disc specimens were obtained from caries-free extracted third human molars and divided in 8 groups (n = 5). Percentage of permeability (%Lp) was assessed in a dental permeability machine considering hydraulic conductance, immediately after pastes application and at day 7, day 14, and day 21. The precipitates formed on the surface of the dentin discs (and dentinal tubules) were analyzed by SEM/EDS and micro-Raman spectra. Data of dentin permeability (%) 2-way repeated-measures (ANOVA) and Holm-Sidak post-tests (α = 0.05). Dentinal tubule obliteration was visually (and elemental) evaluated and descriptively reported. RESULTS: The experimental bioactive glass pastes containing NbG and 45S5, regardless of the concentration, reduced dentin permeability in comparison with pastes without bioactive glasses (P < 0.05). The formulated placebo and commercial paste did not reduce permeability over time (P < 0.05). SEM/EDS and micro-Raman analyses showed that both type of bioactive pastes (NbG or 45S5-based) presented mineral precipitates obliterating the dentinal tubules at day 21. NbG seems to offer a better initial effect than 45S5, while at 21 days there is no difference between both glasses. CONCLUSION: Experimental bioactive pastes containing NbG and 45S5 (at concentrations of 10%, 20%, or 30%) have potential to reduce dentin permeability (over time) in comparison with pastes without bioactive glasses; and this occurs on behalf of obliteration of dentinal tubules by microparticle and precipitate formation. CLINICAL RELEVANCE: Bioactive pastes containing NbG and 45S5 may benefit patients presenting dentin hypersensitivity, because these pastes can start acting fast after application and maintain their action up to 21 days.

One-year prospective nerve conduction study of thalidomide neuropathy in lupus erythematosus: Incidence, coasting effect and drug plasma levels.

BACKGROUND: Few prospective studies in cutaneous and systemic lupus erythematosus (CLE/SLE) assessed thalidomide-induced peripheral neuropathy (TiPN) incidence/reversibility, and most have not excluded confounding causes neither monitored thalidomide plasma levels. OBJECTIVES: To evaluate TiPN incidence/reversibility, coasting effect and its association with thalidomide plasma levels in CLE/SLE. METHODS: One-year prospective study of thalidomide in 20 CLE/SLE patients without pregnancy potential, with normal nerve conduction study (NCS), and excluded other PN causes. Thalidomide levels were determined by high-performance liquid chromatography/tandem mass spectrometry. RESULTS: Twelve patients (60%) developed TiPN: 33.3% were symptomatic and 66.6% asymptomatic. Half of this latter group developed coasting effect (TiPN symptoms 1-3 months after drug withdrawal). The main predictive factors for TiPN were treatment duration ≥6 months (p = 0.025) and cumulative dose (p = 0.023). No difference in plasma thalidomide levels between patients with/without TiPN was observed (p = 0.464). After drug withdrawal, 75% symptomatic TiPN patients improved their symptoms. Seven TiPN patients underwent an additional NCS after drug withdrawal: 42.8% worsened NCS, 14.2% was stable, and 42.8% had improved NCS. CONCLUSION: Our data provides novel evidence of coasting effect in half of asymptomatic patients with TiPN. The irreversible nature of this lesion in 25% of TiPN patients reinforces the relevance of early NCS monitoring, and suggests thalidomide use solely as a bridge for other effective therapy for refractory cutaneous lupus patients.

Methods for prevention of early childhood caries: Overview of systematic reviews.

Early childhood caries (ECC) is a global problem, disproportionately affecting disadvantaged populations. The aim of this study was to evaluate systematically the available scientific evidence on the effectiveness of methods for ECC prevention. Six electronic databases were searched. Two independent reviewers selected the publications and analysed the quality of the included systematic reviews. Thirteen studies were included. Overall, eight reviews were classified with methodological quality critically low using the AMSTAR 2, whereas five reviews achieved a high risk of bias using the ROBIS tool. The methods identified that were positively related to the prevention of ECC were as follows: preventive dental programmes for pregnant women; advice on diet and feeding; prenatal oral health care; integration of maternal and children's oral health promotion into nursing practice; maternal oral health programmes undertaken by non-dental health professionals; dental health education in combination with the use of fluoride for children; early preventive dental visits; and the use of fluoride varnish and toothpastes with more than 1000 ppm of fluoride. The currently available evidence supporting the effectiveness of methods for prevention of ECC, although suggesting some methods of greater potential, is still lacking due to the methodological quality of the systematic reviews and the included primary studies.

Planetary health in the Anthropocene.

The idea that the Holocene is over and a new human-dominated geological epoch, the Anthropocene, is in progress has been widely discussed. The article aims to outline the published definitions and current patterns on the Anthropocene, highlighting an agenda of emerging risks, challenges and possibilities for the health of the world's population in this new era. We performed a review on the complexities of planetary health in the Anthropocene, which generated 42 initial references for full-text reading; we selected 25 of them and carried out analysis and interpretation. Anthropogenic activities have increasing impacts on the environment and a fundamental change in the relationship between humans and the terrestrial system, in many ways that exert intentional and unintentional influences on natural and social processes. The burgeoning literature on health promotion and global public health talks about the anthropogenic forces, claiming a solid critical theory of action to confront, modify and reduce the deleterious effects of such forces. For that reason, the 23rd IUHPE World Conference on Health Promotion, scheduled to be held in New Zealand in 2019, emphasizes the theme 'Promoting Planetary Health and Sustainable Development for All'. It recognizes that the current paradigm of economic unlimited growth and exploitation of limited natural resources is unfair and unsustainable, leading to geopopulational and temporal inequities between generations.

Bone tissue reaction, setting time, solubility, and pH of root repair materials.

OBJECTIVES: This study aims to compare the bone tissue reaction, setting time, solubility, and pH of NeoMTA Plus, Biodentine (BD), and MTA Angelus (MTA-A). MATERIALS AND METHODS: Initial and final setting times (n = 7) and solubility up to 7 days (n = 11) were evaluated in accordance with ASTM C266-15 and ANSI/ADA Specification No. 57, respectively. pH (n = 10) was measured up to 28 days. Bone tissue reactions in 48 rats' femur were histologically analyzed after 7, 30, and 90 days. ANOVA and Tukey's tests compared setting time, solubility, and pH data; bone reactions data were compared by Kruskal-Wallis and Dunn's tests. RESULTS: NeoMTA Plus had longer initial and final setting times than MTA-A and BD (P < 0.05). At 7 days, BD showed the highest solubility, similar to NeoMTA Plus (P > 0.05) and different from MTA-A (P < 0.05). NeoMTA Plus had a progressive mass loss over time; at 7 days, it was significantly different from the initial mass (P < 0.05). BD showed higher pH in the periods assessed when compared to the other materials (P < 0.05). Bone tissue repair had no differences between groups in each experimental period (P > 0.05). All groups presented no difference from 30 to 90 days (P > 0.05) and had better bone repair at 90 days than at 7 days (P < 0.05). CONCLUSIONS: NeoMTA Plus, BD, and MTA-A showed satisfactory setting time, high mass loss, alkaline pH, and allowed bone repair. CLINICAL RELEVANCE: Calcium silicate-based cements are indicated for multiple clinical situations. NeoMTA Plus and BD showed satisfactory physical-chemical and biological properties, being considered as alternatives to MTA-A, as root repair materials for clinical use.

Impact of incorporating ABCB1 and CYP4F2 polymorphisms in a pharmacogenetics-guided warfarin dosing algorithm for the Brazilian population.

PURPOSE: Interpatient variation of warfarin dose requirements may be explained by genetic variations and general and clinical factors. In this scenario, diverse population-calibrated dosing algorithms, which incorporate the main warfarin dosing influencers, have been widely proposed for predicting supposed warfarin maintenance dose, in order to prevent and reduce adverse events. The aim of the present study was to evaluate the impact of the inclusion of ABCB1 c.3435C>T and CYP4F2 c.1297G>A polymorphisms as additional covariates in a previously developed pharmacogenetic-based warfarin dosing algorithm calibrated for the Brazilian population. METHODS: Two independent cohorts of patients treated with warfarin (n = 832 and n = 133) were included for derivation and replication of the algorithm, respectively. Genotyping of ABCB1 c.3435C>T and CYP4F2 c.1297G>A polymorphisms was performed by polymerase chain reaction followed by melting curve analysis and TaqMan® assay, respectively. A multiple linear regression was performed for the warfarin stable doses as a dependent variable, considering clinical, general, and genetic data as covariates. RESULTS: The inclusion of ABCB1 and CYP4F2 polymorphisms was able to improve the algorithm's coefficient of determination (R2) by 2.6%. In addition, the partial determination coefficients of these variants revealed that they explained 3.6% of the warfarin dose variability. We also observed a marginal improvement of the linear correlation between observed and predicted doses (from 59.7 to 61.4%). CONCLUSION: Although our study indicates that the contribution of the combined ABCB1 and CYP4F2 genotypes in explaining the overall variability in warfarin dose is not very large, we demonstrated that these pharmacogenomic data are statistically significant. However, the clinical relevance and cost-effective impact of incorporating additional variants in warfarin dosing algorithms should be carefully evaluated.

Tranexamic acid as a local hemostasis method after dental extraction in patients on warfarin: a randomized controlled clinical study.

OBJECTIVES: The present work is a controlled, blinded, and randomized clinical trial comparing hemostatic measures for the control of post-tooth extraction hemorrhage in patients on anticoagulation therapy with warfarin. MATERIALS AND METHODS: The sample consisted of 37 patients (37.8% male and 62.2% female) with a mean age of 45.5 years. After randomization, 20 patients were allocated to the control group (conventional hemostasis measures) and 17 to the study group (addition of local tranexamic acid). All variables that could influence the outcome were similar between the groups and no significant difference was seen (p > 0.05). RESULTS: In the assessment of immediate hemostasis, for the control group, the time to achieve cessation of bleeding was 9.1 (± 3.6) minutes. For the study group this was much lower, and this difference (6.018 / confidence interval of 95%, 4.677 to 7.359) was statistically significant (p < 0.001). In evaluating the control of intermediate hemorrhage, the use of tranexamic acid was more significantly associated with the absence of bleeding, especially in the first 24 h. CONCLUSIONS AND CLINICAL RELEVANCE: Thus, this measure of local hemostasis in topical form with gauze compression and irrigation was shown to be more effective in reducing the time to attain immediate hemostasis, and in preventing intermediate hemorrhage.

Effect of different endodontic sealers and time of cementation on push-out bond strength of fiber posts.

OBJECTIVES: This study aims to evaluate the effect of different endodontic sealers (epoxy resin, eugenol, and bioceramic/calcium silicate-based) and the time of cementation (immediately or 7 days after canal obturation) on the bond strength of a fiberglass post cemented with RelyX™ ARC. MATERIAL AND METHODS: Eighty-four premolars were instrumented and divided into groups (n = 12) according to the sealer and the time of post cementation: Endofill (EN), Endosequence BC Sealer (BC), and AH Plus (AH) had immediately fiber post cementation; EN7, BC7, and AH7 had post cementation after 7 days; and control group (C) had fiber post cementation without endodontic sealer. Each post space of the root was cut into slices and submitted to push-out test. Failure mode was assessed. Two-way ANOVA, Tukey's, and Dunnett's tests were used for statistical analysis (α = 5%). RESULTS: The type of endodontic sealer (p < 0.001), the time of post cementation (p = 0.038), and the interaction sealer time (p = 0.002) had negative influence on bond strength of fiberglass posts cemented with RelyX™ ARC. AH promoted the highest bond strength mean values (21.20 MPa immediately and 15.54 MPa at 7 days). EN (9.75 MPa immediately and 13.15 MPa at 7 days) and BC (10.43 MPa immediately and 5.73 MPa at 7 days) had lower bond strength than AH, regardless the time of cementation. CONCLUSIONS: AH was the best sealer to obturate the root canal when fiberglass cementation with resin-based cement is planned. CLINICAL RELEVANCE: The correct choice of an endodontic sealer and the adequate time of post cementation may avoid post dislocation caused by low bond strength to dentin.

Redox Remodeling Is Pivotal in Murine Diaphragm Muscle Adaptation to Chronic Sustained Hypoxia.

Mechanisms underpinning chronic sustained hypoxia (CH)-induced structural and functional adaptations in respiratory muscles are unclear despite the clinical relevance to respiratory diseases. The objectives of the present study were to thoroughly assess the putative role of CH-induced redox remodeling in murine diaphragm muscle over time and the subsequent effects on metabolic enzyme activities, catabolic signaling and catabolic processes, and diaphragm muscle contractile function. C57Bl6/J mice were exposed to normoxia or normobaric CH (fraction of inspired oxygen = 0.1) for 1, 3, or 6 weeks. A second cohort was exposed to CH for 6 weeks with and without antioxidant supplementation (tempol or N-acetyl cysteine). After CH exposure, we performed two-dimensional redox proteomics with mass spectrometry, enzyme activity assays, and cell-signaling assays on diaphragm homogenates. We also assessed diaphragm isotonic contractile and endurance properties ex vivo. Global protein redox changes in the diaphragm after CH are indicative of oxidation. Remodeling of proteins key to contractile, metabolic, and homeostatic functions was observed. Several oxidative and glycolytic enzyme activities were decreased by CH. Redox-sensitive chymotrypsin-like proteasome activity of the diaphragm was increased. CH decreased phospho-forkhead box O3a (FOXO3a) and phospho-mammalian target of rapamycin content. Hypoxia-inducible factor-1α and phospho-p38 mitogen-activated protein kinase content was increased in CH diaphragm, and this was attenuated by antioxidant treatment. CH exposure decreased force- and power-generating capacity of the diaphragm, and this was prevented by antioxidant supplementation with N-acetyl cysteine but not tempol. Redox remodeling is pivotal for diaphragm adaptation to CH, affecting metabolic activity, atrophy signaling, and functional performance. Antioxidant supplementation may be useful as an adjunctive therapy in respiratory-related diseases characterized by hypoxic stress.

Differential proteomics of dehydration and rehydration in bryophytes: evidence towards a common desiccation tolerance mechanism.

All bryophytes evolved desiccation tolerance (DT) mechanisms during the invasion of terrestrial habitats by early land plants. Are these DT mechanisms still present in bryophytes that colonize aquatic habitats? The aquatic bryophyte Fontinalis antipyretica Hedw. was subjected to two drying regimes and alterations in protein profiles and sucrose accumulation during dehydration and rehydration were investigated. Results show that during fast dehydration, there is very little variation in protein profiles, and upon rehydration proteins are leaked. On the other hand, slow dehydration induces changes in both dehydration and rehydration protein profiles, being similar to the protein profiles displayed by the terrestrial bryophytes Physcomitrella patens (Hedw.) Bruch and Schimp. and, to what is comparable with Syntrichia ruralis (Hedw.) F. Weber and D. Mohr. During dehydration there was a reduction in proteins associated with photosynthesis and the cytoskeleton, and an associated accumulation of proteins involved in sugar metabolism and plant defence mechanisms. Upon rehydration, protein accumulation patterns return to control values for both photosynthesis and cytoskeleton whereas proteins associated with sugar metabolism and defence proteins remain high. The current results suggest that bryophytes from different ecological adaptations may share common DT mechanisms.

Production of MMP-9 and inflammatory cytokines by Trypanosoma cruzi-infected macrophages.

Matrix metalloproteinases (MMPs) constitute a large family of Zn(2+) and Ca(2+) dependent endopeptidases implicated in tissue remodeling and chronic inflammation. MMPs also play key roles in the activation of growth factors, chemokines and cytokines produced by many cell types, including lymphocytes, granulocytes, and, in particular, activated macrophages. Their synthesis and secretion appear to be important in a number of physiological processes, including the inflammatory process. Here, we investigated the interaction between human and mouse macrophages with T. cruzi Colombian and Y strains to characterize MMP-9 and cytokine production in this system. Supernatants and total extract of T. cruzi infected human and mouse macrophages were obtained and used to assess MMP-9 profile and inflammatory cytokines. The presence of metalloproteinase activity was determined by zymography, enzyme-linked immunosorbent assay and immunoblotting assays. The effect of cytokines on MMP-9 production in human macrophages was verified by previous incubation of cytokines on these cells in culture, and analyzed by zymography. We detected an increase in MMP-9 production in the culture supernatants of T. cruzi infected human and mouse macrophages. The addition of IL-1ß or TNF-α to human macrophage cultures increased MMP-9 production. In contrast, MMP-9 production was down-modulated when human macrophage cultures were treated with IFN-γ or IL-4 before infection. Human macrophages infected with T. cruzi Y or Colombian strains produced increased levels of MMP-9, which was related to the production of cytokines such as IL-1ß, TNF-α and IL-6.

Equity-diversity-inclusion (EDI)-related strategies used by dental schools during the admission/selection process: a narrative review.

INTRODUCTION: Decades of evidence have demonstrated a lack of workforce diversity and sustaining disparities in academic dentistry and professional practice. Underrepresented minority students may face challenges and implicit bias during the dental schools' admission/selection process. This review collected papers from different countries to summarize the Equity-Diversity-Inclusion (EDI)-related strategies that dental schools worldwide have used in their admissions process to increase diversity. METHODS: A comprehensive search using MEDLINE (via PubMed), ERIC, Cochrane Reviews, Cochrane Trials, American Psychological Association Psyc Info (EBSCO) and Scopus was done between January and March-2023. All types of articles-designs were included, except comments and editorials, and all articles selected were in English. Two independent investigators screened the articles. Extracted data were general characteristics, study objectives, and EDI-related strategies. RESULTS: Sixteen publications were used to construct this manuscript. The year with the greatest number of publications was 2022. Type of studies were case studies/critical reviews (50%), cross-sectional (including survey and secondary data analysis) (n = 5, 31.25%), qualitative methods of analysis (n = 2, 12.5%), and retrospective/secondary data collection (n = 1, 6.25%). The strategies described in the articles were related to (1) considering the intersectionality of diversity, (2) using noncognitive indicators during the school admissions process to construct a holistic selection process, (3) diversifying, professionalizing, and providing training to admissions persons who had leadership roles with the support from the dental school and the university, and (4) allocating financial investments and analyzing current policies and procedures regarding EDI. CONCLUSIONS: This review aggregated interesting findings, such as: some schools are considering the intersectionality of diversity as a way to include underrepresented minorities and to diversify the students-body. The recent growth in publications on EDI during dental admission/selection process might indicate a positive movement in this field.