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Brazilian green propolis is used in folk medicine because of its various biological properties. The hydroalcoholic extract of Brazilian green propolis is characteristic for possessing several pharmacological properties. Phytochemical investigations have attributed some of these properties to the presence of compounds, which were chosen as analytical markers. This paper reports the development and analytical validation using UPLC-MS/MS in MRM mode. Veratraldehyde was used as an internal standard in qualitative and quantitative analyses of the extracts. Relative standard deviation values obtained for intra-day and inter-day precision were lower than 4%. Of the five parameters for robustness, wavelength detection and flow rate were the critical ones. Limits of detection and quantification ranged from 0.300 to 39.500 ng.mL -1 and from 1.400 to 85.00 ng.mL -1 , respectively. The recoveries were between 94.00 and 119.00%, with relative standard deviation values around 5.0%. The developed method is precise, sensitive, and reliable for analysing Brazilian green propolis.

Antifungal therapy, especially with the azoles, could promote the incidence of less susceptible isolates of Cryptococcus neoformans and C. gattii species complexes (SC), mostly in developing countries. Given that these species affect mostly the immunocompromised host, the infections are severe and difficult to treat. This review encompasses the following topics: 1. infecting species and their virulence, 2. treatment, 3. antifungal susceptibility methods and available categorical endpoints, 4. genetic mechanisms of resistance, 5. clinical resistance, 6. fluconazole minimal inhibitory concentrations (MICs), clinical outcome, 7. environmental influences, and 8. the relevance of host factors, including pharmacokinetic/pharmacodynamic (PK/PD) parameters, in predicting the clinical outcome to therapy. As of now, epidemiologic cutoff endpoints (ECVs/ECOFFs) are the most reliable antifungal resistance detectors for these species, as only one clinical breakpoint (amphotericin B and C. neoformans VNI) is available.

Ethnopharmacological Relevance: Brazilian red propolis is a natural product known due to its medicinal properties. The efficacy of this natural resin has been proved; however, few studies report the safety of its oral use. Some toxic effects of natural products may not be expressed in traditional use, and preclinical studies are necessary to guarantee their safety. Health regulatory agency currently requires these non-clinical studies to develop drugs and herbal medicines, including genotoxic and oral toxicity tests., Aim of the Study: Accomplish the preclinical toxicity studies of Brazilian red propolis extract (BRP) in rodents, including genotoxicity, acute and sub-chronic toxicities., Material and Methods: Genotoxicity assays followed the erythrocyte micronucleus test protocol in a range of 500-2000 mg/kg BRP oral treatment on male Swiss mice. After an up-and-down procedure, acute oral toxicity (single dose) was performed on female Wistar Hannover rats, reaching a 2000 mg/kg BRP oral gavage concentration. Animals were monitored periodically until 14 days and euthanized for a macroscopic necropsy analysis. The sub-chronic oral toxicity test (90 days) was achieved with 1000 mg/kg of BRP on Wistar Hannover rats (males/females). Animals were monitored to evaluated behavioral and biometrical changes, then were euthanized to perfomed hematological, biochemical, and histopathological analyses., Results: No genotoxic effect of the BRP was detected. The acute toxicity indicated no toxicity of a single oral dose of 2000 mg/kg of BRP. The long-term oral toxicity performed with 1000 mg/kg of BRP altered water and food intake and the biometrics, hematological and biochemical parameters. Biochemical alterations in hepatic and renal parameters were detected only in the males. Despite the detection of biochemical alterations, no histopathological changes were detected in the organs of any group., Conclusions: BRP, at a higher dose, showed no signs of immediate toxicity. However, the obtained results suggest that the chemical composition and the intake of higher doses deserve special attention regarding possible toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Glomerulopathy with fibronectin deposits is an autosomal dominant disease associated with proteinuria, hematuria, hypertension and renal function decline. Forty percent of the cases are caused by mutations in FN1, the gene that encodes fibronectin., Case Presentation: This report describes two cases of Glomerulopathy with fibronectin deposits, involving a 47-year-old father and a 14-year-old son. The renal biopsies showed glomeruli with endocapillary hypercellularity and large amounts of mesangial and subendothelial eosinophilic deposits. Immunohistochemistry for fibronectin was markedly positive. Whole exome sequencing identified a novel FN1 mutation that leads to an amino-acid deletion in both patients (Ile1988del), a variant that required primary amino-acid sequence analysis for assessment of pathogenicity. Our primary sequence analyses revealed that Ile1988 is very highly conserved among relative sequences and is positioned in a C-terminal FN3 domain containing heparin- and fibulin-1-binding sites. This mutation was predicted as deleterious and molecular mechanics simulations support that it can change the tertiary structure and affect the complex folding and its molecular functionality., Conclusion: The current report not only documents the occurrence of two GFND cases in an affected family and deeply characterizes its anatomopathological features but also identifies a novel pathogenic mutation in FN1, analyzes its structural and functional implications, and supports its pathogenicity.

Objectives: To evaluate the influence of temperature of evaporation in adhesive systems with different solvents on the apparent modulus of elasticity and mass change of macro-hybrid layers modified by proanthocyanidins (PACs)., Methods: Adhesive resin beams (A) from Single Bond Plus (SB), Excite (EX) and One Step Plus (OS) were prepared after solvent evaporation at 23°C or 40°C (n=12). Macro-hybrid layers (M) (n=12) were prepared using demineralized dentin beams sectioned from extracted human third molars. The demineralized dentin specimens were infiltrated with each one of the three adhesive systems at 23°C or 40°C; with or without prior dentin treatment with PACs for 10min. The apparent modulus of elasticity (E) and mass change (Wmc, %) of adhesives beams and resin-infiltrated specimens were assessed in dry and wet conditions after immersion in water (24h, 1, 3 and 6 months). The E was statistically analyzed by Tukey-Kramer test and the Wmc, % by Kruskal Wallis, and Dunn (α=0.05)., Results: Solvent evaporation at 40°C resulted in higher E values for adhesive resin beams at all storage conditions, regardless of the adhesive system (p<0.05). Increased mass loss (3 months: -0.01%; 6 months: -0.05%) was observed in One Step resin beams (p≤0.05). In the macro-hybrid layer models the pretreatment with PACs along with solvent evaporation at 40°C increased E and decreased the Wmc, % (3 months: -2.5; 6 months: 2.75%) for adhesives evaluated over time (p<0.05). No significant differences in ratio (resin/dentin) were found for the macro-hybrid layers (p>0.05)., Significance: Improved solvent evaporation at higher temperature, and increased collagen cross-linking induced by PACs, enhanced the mechanical properties resulting in highly stable macro-hybrid layers over 6 months storage., (Copyright © 2016 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.)

Objective: This study evaluated the impact of the distance between the light guide tip of the curing unit and material surface on the degree of conversion and Knoop microhardness of a composite resin., Materials and Methods: Circular samples were carried out of a methacrylate micro-hybrid resin-based composite and light cured at 0, 2 and 4 mm distance. Monomer conversion rate was measured using a Fourier-transform Raman spectrometer and Knoop hardness number was obtained using a microhardness tester on the top and bottom surfaces. Data were statistically analyzed by analysis of variance and Tukey's test (α=0.05)., Results: Overall, the increase of curing distance reduced the microhardness (p≤0.05), but did not influence the carbon double bond conversion rate (p>0.05) of the composite resin tested; and the top surface showed better properties compared to the bottom (p≤0.05)., Conclusions: The light curing at distance can reduce mechanical properties and could affect long-term durability of the composite restorations. Thus, the use of a curing device with high irradiance is recommended.

Background: Cervical cancer ranks third in prevalence and fourth as cause of death in women worldwide. In Brazil, 17,540 women were diagnosed in 2012 with the disease. Persistent infection with high-risk HPV types is a necessary condition for the development of pre-invasive and invasive cervical neoplasia. Currently, over 100 HPV types have been identified, but HPV16 and 18 are recognized as the mayor culprits in cervical carcinogenesis. Our objective was to assess the relationships between single- (ST) and multiple-type (MT) HPV infections with patients' age and lesion pathological status., Methods: 328 patients with either squamous or glandular intraepithelial or invasive cervical lesion were selected. All subjects were tested for HPV genotypes with reverse hybridization for 21 high- (hr-HPV) and 16 low-risk (lr-HPV) probes. Prevalence of ST and MT HPV infections was compared across histological types and age strata., Results: 287 (87%) women had at least one HPV type detected and 149 (52%) had MT infections. The most prevalent HPV type was HPV16, present in 142 cases (49% of all HPV-positive cases), followed by HPV58, 52, 31, 35 and 33. HPV18, in single or multiple infections, occurred in 23 cases (8% of hr-HPV cases). Almost all glandular lesions were associated with HPV16 and 18 alone. Multiple infections were significantly more prevalent in squamous than in glandular lesion for HPV16 and 18 (P = 0.04 and 0.03 respectively). The prevalence of MT infections followed a bimodal distribution; peaking in women younger 29 years and in those aged 50 to 59., Conclusions: Our data indicate that prevention strategies for pre-invasive and invasive squamous lesions should be focused on HPV16 and a few alpha-9 HPV types. It is clear to us that in young women, prophylaxis must cover a large amalgam of HPV types beyond classic HPV16 and 18.

Pigments of food and beverages could affect dental bleaching efficacy. The aim of this investigation was to evaluate color change and mineral loss of tooth enamel as well as the influence of staining solutions normally used by adolescent patients undergoing home bleaching. Initial hardness and baseline color were measured on enamel blocks. Specimens were divided into five groups (n=5): G1 (control) specimens were kept in artificial saliva throughout the experiment (3 weeks); G2 enamel was exposed to 10% carbamide peroxide for 6 h daily, and after this period, the teeth were cleaned and stored in artificial saliva until the next bleaching session; and G3, G4, and G5 received the same treatments as G2, but after bleaching, they were stored for 1 h in cola soft drink, melted chocolate, or red wine, respectively. Mineral loss was obtained by the percentage of hardness reduction, and color change was determined by the difference between the data obtained before and after treatments. Data were subjected to analysis of variance and Fisher's test (α=0.05). G3 and G5 showed higher mineral loss (92.96 ± 5.50 and 94.46 ± 1.00, respectively) compared to the other groups (p ≤ 0.05). G5 showed high-color change (9.34 ± 2.90), whereas G1 presented lower color change (2.22 ± 0.44) (p ≤ 0.05). Acidic drinks cause mineral loss of the enamel, which could modify the surface and reduce staining resistance after bleaching.

Background and Objectives: Low central venous oxygen saturation (ScvO₂) indicates an imbalance between cellular oxygen supply and consumption and, consequently, worse prognosis for critical patients. However, it is not clear what the value of this marker in surgical patients. The objective of the present study was to evaluate whether low perioperative ScvO₂ determines a worse prognosis., Methods: This is a 6-month observational study carried on in a tertiary hospital. Patients who needed to be in the intensive care unit (ICU) postoperatively, with age ≥ 18 years, who underwent large surgeries, were included. Patients who underwent palliative surgeries and those with severe heart failure were excluded. Levels of ScvO₂ were measured before the surgery, during the procedure, and after the surgery in the ICU., Results: Sixty-six patients were included in this study, but 25.8% of them did not survive. Mean ScvO₂ levels were higher intraoperatively, 84.7 ± 8.3%, than preoperatively and in the ICU, 74.1 ± 7.6% and 76.0 ± 10.5% (p = 0.0001), respectively. However, only preoperative SvcO₂ levels of non-surviving patients were significantly lower than those who survived. By logistic regression, preoperative ScvO₂, OR = 0.85 (95% CI 0.74-0.98) (p = 0.02), was an independent factor of in-hospital mortality. Patients with preoperative ScvO₂ < 70% had greater need of intraoperative blood transfusion (80.0% versus 37.0%, p = 0.001) and volume replacement, 8,000.0 (6,500.0-9,225.0) mL versus 6,000.0 (4,500.0-8,500.0) mL (p = 0.04), with greater chances of postoperative complications (75% versus 45.7%, p = 0.02) and longer time in the ICU, 4.0 (20.0-5.0) days versus 3.0 (1.7-4.0) days (p = 0.02)., Conclusions: Intraoperative ScvO₂ levels are higher than those both in the pre- and postoperative period. However, low preoperative ScvO₂ determines worse prognosis., (© 2010 Elsevier Editora Ltda. All rights reserved.)