Advances in surface design and biomedical applications of magnetic nanoparticles.

Despite significant efforts by scientists in the development of advanced nanotechnology materials for smart diagnosis devices and drug delivery systems, the success of clinical trials remains largely elusive. In order to address this biomedical challenge, magnetic nanoparticles (MNPs) have gained attention as a promising candidate due to their theranostic properties, which allow the simultaneous treatment and diagnosis of a disease. Moreover, MNPs have advantageous characteristics such as a larger surface area, high surface-to-volume ratio, enhanced mobility, mass transference and, more notably, easy manipulation under external magnetic fields. Besides, certain magnetic particle types based on the magnetite (Fe3O4) phase have already been FDA-approved, demonstrating biocompatible and low toxicity. Typically, surface modification and/or functional group conjugation are required to prevent oxidation and particle aggregation. A wide range of inorganic and organic molecules have been utilized to coat the surface of MNPs, including surfactants, antibodies, synthetic and natural polymers, silica, metals, and various other substances. Furthermore, various strategies have been developed for the synthesis and surface functionalization of MNPs to enhance their colloidal stability, biocompatibility, good response to an external magnetic field, etc. Both uncoated MNPs and those coated with inorganic and organic compounds exhibit versatility, making them suitable for a range of applications such as drug delivery systems (DDS), magnetic hyperthermia, fluorescent biological labels, biodetection and magnetic resonance imaging (MRI). Thus, this review provides an update of recently published MNPs works, providing a current discussion regarding their strategies of synthesis and surface modifications, biomedical applications, and perspectives.

Effect of cationic surfactant on the physicochemical and antibacterial properties of colloidal systems (emulsions and microemulsions).

Colloidal systems have been used to encapsulate, protect and release essential oils in mouthwashes. In this study, we investigated the effect of cetylpyridinium chloride (CPC) on the physicochemical properties and antimicrobial activity of oil-in-water colloidal systems containing tea tree oil (TTO) and the nonionic surfactant polysorbate 80. Our main aim was to evaluate whether CPC could improve the antimicrobial activity of TTO, since this activity is impaired when this essential oil is encapsulated with polysorbate 80. These systems were prepared with different amounts of TTO (0-0.5% w/w) and CPC (0-0.5% w/w), at a final concentration of 2% (w/w) polysorbate 80. Dynamic light scattering (DLS) results revealed the formation of oil-swollen micelles and oil droplets as a function of TTO concentration. Increases in CPC concentrations led to a reduction of around 88% in the mean diameter of oil-swollen micelles. Although this variation was of only 20% for the oil droplets, the samples appearance changed from turbid to transparent. The surface charge of colloidal structures was also markedly affected by the CPC as demonstrated by the transition in zeta potential from slightly negative to highly positive values. Electron paramagnetic resonance (EPR) studies showed that this transition is followed by significant increases in the fluidity of surfactant monolayer of both colloidal structures. The antimicrobial activity of colloidal systems was tested against a Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureaus) bacteria. Our results revealed that the inhibition of bacterial growth is observed for the same CPC concentration (0.05% w/w for E. coli and 0.3% w/w for S. aureus) regardless of TTO content. These findings suggest that TTO may not act as an active ingredient in polysorbate 80 containing mouthwashes.

Study of the

The ^{22}Mg(α,p)^{25}Al reaction rate has been identified as a major source of uncertainty for understanding the nucleosynthesis flow in Type-I x-ray bursts. We report a direct measurement of the energy- and angle-integrated cross sections of this reaction in a 3.3-6.9 MeV center-of-mass energy range using the MUlti-Sampling Ionization Chamber (MUSIC). The new ^{22}Mg(α,p)^{25}Al reaction rate is a factor of ∼4 higher than the previous direct measurement of this reaction within temperatures relevant for x-ray bursts, resulting in the ^{22}Mg waiting point of x-ray burst nucleosynthesis flow to be significantly bypassed via the (α,p) reaction.

Study of the integument that covering back and stinger of the freshwater stingray Potamotrygon rex (Chondricthyes, Potamotrygonidae).

The objective of this study was to describe the histology and histochemistry of the integument covering the back and stinger of the freshwater stingray Potamotrygon rex, endemic to the Middle Upper Tocantins River. The species has a dark back and yellowish circular spots that extend to the tail, which has one to two stings located in the median portion of the tail. Through histological study it was observed that the epithelia of the back and stinger are composed of non-keratinized stratified pavement epithelial tissue, and are organized in three layers: basal, intermediate and superficial. The differences between the tissues are related to the cell types that compose them. The back is organized with epithelial cells, mucus cells, granulocyte cells and chromatophores. The mucus cells are distributed in different layers along the animal's back, influencing the thickness of the tissue. The tissue that covers the stinger is composed of epithelial cells, chromatophores and specialized cells in protein synthesis. In the histochemistry, the stinger epithelial cells were stained with Bromophenol Blue, especially those of the intermediate layer, which were called specialized cells. In the back the epithelial cells were stained with Bromophenol Blue, Alcian Blue and PAS, and the mucous cells with PAS. In both tissues the presence of protein reserves was detected, areas so called because they are stained strongly with Bromophenol Blue. The results show that the stinger presents activity directed to the production of proteins, and that the back is organized to produce different components, which constitute the cuticle that covers the animal's body.

Radiopacity and mechanical properties of dental adhesives with strontium hydroxyapatite nanofillers.

OBJECTIVES: Dental resins filled with hydroxyapatite (HAp) nanoparticles have significantly revolutionized restorative dentistry offering advantages such as remineralization potential and increase of polymerization. However, these materials have limited radiopacity hindering the diagnosis of secondary caries. The present study investigated the development of a new radiopaque dental adhesive by incorporating novel pure strontium hydroxyapatite nanoparticles [Sr10(PO4)6(OH)2, SrHAp] synthesized by a simple hydrothermal method. METHODS: Strontium phosphates were prepared using co-precipitation (SrHAp0h) and hydrothermal treatment for 2 and 5h (SrHAp2h and SrHAp5h). The crystallinity, crystallite size, textural and morphology features of the nanoparticles were characterized by XRD, FT-IR, micro-Raman and TEM. Strontium hydroxyapatite (SrHAp) or calcium hydroxyapatite (HAp) nanoparticles were then incorporated (10 wt%) into an adhesive resin of a commercial three-step etch-and-rinse adhesive to evaluate the radiopacity of disk-shaped specimens, degree of conversion (DC) assessed by FT-IR and mechanical properties by three-point bending test. The unfilled adhesive was used as negative control. RESULTS: While SrHAp0h and SrHAp2h resulted a phase mixing, the pure and highly crystalline phase of strontium hydroxyapatite free of calcium was obtained with 5h hydrothermal treatment (SrHAp5h). The TEM images revealed nanorods morphology for SrHAp5h. SrHAps incorporated into adhesive showed higher radiopacity, no alteration on DC despite slightly reducing the mechanical properties. SIGNIFICANCE: Although the mechanical properties are slightly impaired, incorporation of SrHAp nanoparticles offers potential method to improve radiopacity of restorative dental resins, easing the tracking of actual remineralization effects and enabling diagnosis of recurrent caries.

Targetable gene fusions identified in radioactive iodine refractory advanced thyroid carcinoma.

Objective Gene alterations leading to activation of the MAPK pathway are of interest for targeted therapy in patients with advanced radioactive iodine refractory (RAI-R) thyroid carcinoma. Due to technical reasons gene fusion analysis in RNA isolated from formalin-fixed tumor tissues has till now been limited. The objective of the present study was to identify targetable gene rearrangements in RNA isolated from formalin-fixed RAI-R thyroid carcinomas. Design Retrospective study in 132 patients with RAI-R thyroid carcinoma (59 papillary-, 24 follicular-, 35 Hürthle cell- and 14 anaplastic thyroid carcinoma). Methods Total nucleic acid (undivided DNA and RNA) was isolated from formalin-fixed tissue. Extensive gene fusion analysis was performed in all samples that tested negative for pathogenic BRAF, NRAS, HRAS and KRAS variants. Results Seven targetable gene fusions were identified in the remaining 60 samples without known DNA variants. This includes frequently reported gene fusions such as CCDC6/RET (PTC1), PRKAR1A/RET (PTC2) and ETV6/NTRK3 , and gene fusions that are less common in thyroid cancer (TPM3/NTRK1, EML4/ALK and EML4/NTRK3). Of note, most gene fusions were detected in papillary thyroid carcinoma and MAPK-associated alterations in Hürthle cell carcinomas are rare (2/35). Conclusion Targetable gene fusions were found in 12% of RAI-R thyroid carcinoma without DNA variants and can be effectively identified in formalin-fixed tissue. These gene fusions might provide a preclinical rationale to include specific kinase inhibitors in the treatment regimen for these patients. The latter intends to restore iodine transport and/or take advantage of the direct effect on tumor cell vitality once progressive disease is seen.

Ultrafast sonochemistry-based approach to coat TiO2 commercial particles for sunscreen formulation.

TiO2 is a common inorganic filter used in sunscreens due to its photoprotective effect on the skin against UV radiation. However, the use of this kind of material in cosmetics is limited by its inherent photocatalytic activity. It is known that coating on TiO2 surface can improve some features. Although, many of the methodologies used for this purpose are still laborious and time-consuming. Thus, this work reports a novel, easy, cheap and fast strategy to coat TiO2 particles by using a sonochemistry approach, aiming to decrease photocatalytic activity and to enhance colloidal stability. For this proposal, SiO2, Al2O3, ZrO2 and sodium polyacrylate (PAANa) were used to tune the surface of commercial TiO2 particles and they were applied in a sunscreen formulation. The samples were characterized by XRPD, FT-IR, DLS, EDS, SEM and TEM. The photocatalytic activity and UV-shielding ability were also evaluated. The sunscreen formulations were prepared and characterized by zeta potential, DLS, and Sun Protection Factor (SPF). FT-IR, EDS, and charge surface of the particles confirmed the success of the sonochemistry coating. Additionally, TiO2@Al2O3, TiO2@SiO2 and TiO2@PAANa show a lower photocatalytic activity than original TiO2 with similar UV-shielding ability. The sunscreens produced with the coated TiO2 have similar SPF to the one with commercial TiO2. Specifically, the sunscreen with TiO2@PAANa shows an increase in colloidal stability. Herein, the incorporation of the sonochemical-coated TiO2 particles in sunscreen formulations may produce sunscreens with better aesthetic appearance and a greater health security due to its lower free radicals production.

Short-term carcinogenesis evaluation of Casearia sylvestris

Abstract Casearia sylvestris Sw., Salicaceae, is an important medicinal plant widely used in Brazil for the treatment of various cardiovascular disorders. This species was included as of interest by Brazilian Unified Health System. Although preclinical studies described cardiovascular protective effects and apparent absence of toxicity, no studies have evaluated its carcinogenic potential. In this study, we proposed a short-term carcinogenesis evaluation of C. sylvestris in Wistar rats, aiming to check the safety of this species to use it as proposed by Brazilian Unified Health System. C. sylvestris leaves were obtained and the crude extract was prepared by maceration from methanol/water. Wistar rats were orally treated for 12 weeks with 50, 250 or 500 mg kg−1 of crude extract or vehicle. Body weight, daily morbidity and mortality were monitored. Blood and bone marrow samples were collect for micronucleus test, comet assay and tumor markers evaluation. Vital organs were removed to macro and histopathological analyses. The crude extract did not induce mutagenic and genotoxic effects and no alterations were observed in important tumor markers. Finally, no detectable signs of injury through gross pathology or histopathological examinations were observed. Our results certify the absence of the crude extract toxicity, indicating its safety, even at prolonged exposure as proposed by Brazilian Unified Health System.

Microbiological contamination in peanut confectionery processing plants.

AIMS: In order to investigate Enterobacteriaceae, coliforms, Escherichia coli and Salmonella contamination, a survey was conducted at three peanut confectionery processing companies (A, B and C) in Brazil. METHODS AND RESULTS: Samples of different peanut confectionery products (n = 59), peanut raw material (n = 30), manufacturing environment (n = 116) and workers' hand surfaces (n = 12) were analysed. Salmonella and E. coli were not detected in any final product or raw material analysed. Enterobacteriaceae was isolated from 15% of final products. Coliforms were detected in only one sample. Referring to the raw material, six samples showed contamination by Enterobacteriaceae and three samples by coliforms. For the process environment, 19% and 11% of samples presented Enterobacteriaceae and coliforms. Escherichia coli was detected in 5% of samples, and one of these samples tested positive for Salmonella; this strain was serotyping as S. Heidelberg. All food handlers surveyed in Company C showed Enterobacteriaceae and coliforms on their hands. Escherichia coli was isolated from one food worker's hand. CONCLUSION: The results showed that the manufacturing environment, including food handlers were considered the main sources for possible contamination of peanut confectionery products. SIGNIFICANCE AND IMPACT OF THE STUDY: This has been the first study to investigate the occurrence of Salmonella and other Enterobacteriaceae throughout peanut confectionery processing lines. The results might be used to assist risk assessment studies and to establish more effective control measures.

Novel hydroxyapatite nanorods improve anti-caries efficacy of enamel infiltrants.

OBJECTIVES: Enamel resin infiltrants are biomaterials able to treat enamel caries at early stages. Nevertheless, they cannot prevent further demineralization of mineral-depleted enamel. Therefore, the aim of this work was to synthesize and incorporate specific hydroxyapatite nanoparticles (HAps) into the resin infiltrant to overcome this issue. METHODS: HAps were prepared using a hydrothermal method (0h, 2h and 5h). The crystallinity, crystallite size and morphology of the nanoparticles were characterized through XRD, FT-IR and TEM. HAps were then incorporated (10wt%) into a light-curing co-monomer resin blend (control) to create different resin-based enamel infiltrants (HAp-0h, HAp-2h and HAp-5h), whose degree of conversion (DC) was assessed by FT-IR. Enamel caries lesions were first artificially created in extracted human molars and infiltrated using the tested resin infiltrants. Specimens were submitted to pH-cycling to simulate recurrent caries. Knoop microhardness of resin-infiltrated underlying and surrounding enamel was analyzed before and after pH challenge. RESULTS: Whilst HAp-0h resulted amorphous, HAp-2h and HAp-5h presented nanorod morphology and higher crystallinity. Resin infiltration doped with HAp-2h and HAp-5h caused higher enamel resistance against demineralization compared to control HAp-free and HAp-0h infiltration. The inclusion of more crystalline HAp nanorods (HAp-2h and HAp-5h) increased significantly (p<0.05) the DC. SIGNIFICANCE: Incorporation of more crystalline HAp nanorods into enamel resin infiltrants may be a feasible method to improve the overall performance in the prevention of recurrent demineralization (e.g. caries lesion) in resin-infiltrated enamel.

RNA-seq transcriptional profiling of Herbaspirillum seropedicae colonizing wheat (Triticum aestivum) roots.

Herbaspirillum seropedicae is a diazotrophic and endophytic bacterium that associates with economically important grasses promoting plant growth and increasing productivity. To identify genes related to bacterial ability to colonize plants, wheat seedlings growing hydroponically in Hoagland's medium were inoculated with H. seropedicae and incubated for 3 days. Total mRNA from the bacteria present in the root surface and in the plant medium were purified, depleted from rRNA and used for RNA-seq profiling. RT-qPCR analyses were conducted to confirm regulation of selected genes. Comparison of RNA profile of root attached and planktonic bacteria revealed extensive metabolic adaptations to the epiphytic life style. These adaptations include expression of specific adhesins and cell wall re-modeling to attach to the root. Additionally, the metabolism was adapted to the microxic environment and nitrogen-fixation genes were expressed. Polyhydroxybutyrate (PHB) synthesis was activated, and PHB granules were stored as observed by microscopy. Genes related to plant growth promotion, such as auxin production were expressed. Many ABC transporter genes were regulated in the bacteria attached to the roots. The results provide new insights into the adaptation of H. seropedicae to the interaction with the plant.

The impact of patient heterogeneity and socioeconomic factors on abatacept retention in rheumatoid arthritis across nine European countries.

BACKGROUND: There are substantial differences in accessibility to biological disease modifying antirheumatic drugs (bDMARDs) across countries. The objective of this study was to analyse the impact of patient demographics, disease characteristics and gross domestic product (GDP) on abatacept (ABA) retention in patients with rheumatoid arthritis (RA) treated in clinical practice. METHODS: Data from nine European observational RA cohorts of patients treated with ABA were pooled. Kaplan-Meier analysis was used to compare drug retention across registries. Specific causes of drug retention were investigated using competing risks multivariate Cox regression. RESULTS: A total of 3961 patients treated with ABA, with 6188 patient-years of follow-up, were included. Patients in the different national registries had similar demographic features, but varied in baseline disease characteristics. ABA drug retention differed between countries, with median drug retention rates ranging from 1.2 to more than 6 years. The differences in drug retention were marginally explained by disparities in disease characteristics, while the national GDP per capita was strongly associated with drug retention (correlation coefficient -0.74; p=0.02). CONCLUSIONS: Patient characteristics at ABA initiation vary across Europe, probably reflecting differences in eligibility criteria and prescription patterns. However, the difference in ABA drug retention between countries was not primarily explained by disparities in patient characteristics. Lower ABA retention was observed in countries with a more liberal access to bDMARDs and higher GDP. National differences need to be accounted for when pooling data on treatment with bDMARDs from various countries.

Genetic analyses, phenotypic adaptability and stability in sugarcane genotypes for commercial cultivation in Pernambuco.

In the present study, we assessed the agro-industrial performance of 22 sugarcane genotypes adaptable to edaphoclimatic conditions in production microregions in the State of Pernambuco, Brazil, and we recommended the commercial cultivation of select genotypes. The variables analyzed were as follows: sucrose percentage in cane juice, tonnage of saccharose per hectare (TPH), sugarcane tonnage per hectare (TCH), fiber, solid soluble contents, total recoverable sugar tonnage (ATR), and total recoverable sugar tonnage per hectare (ATR t/ha). A randomized block design with 4 repeats was used. Combined variance of the experiments, genetic parameter estimates, and environment stratification were analyzed. Phenotypic adaptability and stability were analyzed using the Annicchiarico and Wricke methods and analysis of variance. Genetic gain was estimated using the classic index and sum of ranks. Genotype selection was efficient for TPH, TCH, and ATR t/ha. Genotypes presented a great potential for improvement and a similar response pattern in Litoral Norte and Mata Sul microregions for TPH and TCH and Litoral Norte and Litoral Sul microregions for ATR t/ha. Genotypes SP78-4764, RB813804, and SP79-101 showed better productivity and phenotypic adaptability and stability, according to the Wricke and Annicchiarico methods. These genotypes can be recommended for cultivation in the sugarcane belt in the State of Pernambuco.

The Effect of Hydrofluoric Acid Concentration on the Bond Strength and Morphology of the Surface and Interface of Glass Ceramics to a Resin Cement.

The purpose of this study was to evaluate the influence of various concentrations of hydrofluoric acid (HF) on the surface/interface morphology and µ-shear bond strength (µSBS) between IPS Empress Esthetic (EST) (Ivoclar Vivadent) and IPS e.max Press (EMX) (Ivoclar Vivadent) ceramics and resin cement. Ceramic blocks were divided into 12 groups for each kind of ceramic. Six different HF concentrations were evaluated: 1%, 2.5%, 5%, 7.5%, 10%, and 15%. All groups were silanated after etching, and half of the specimens within each group received a thin layer of unfilled resin (UR). Three resin cement cylinders were prepared on each ceramic block for µSBS testing. The specimens were stored in distilled water at 37°C for 24 hours. The µSBS test was carried out in a universal testing machine at a crosshead speed of 0.5 mm/min until fracture. The data were submitted to three-way analysis of variance and multiple comparisons were performed using the Tukey post hoc test (p<0.05). The etched surfaces and bonded interfaces were evaluated using scanning electron microscopy. µSBS means (MPa) for 1%, 2.5%, 5%, 7.5%, 10%, and 15% HF concentrations were, respectively, 25.2, 27.2, 30.1, 31.4, 33.3, and 31.8. µSBS means with or without UR application measured 32.24 and 27.4, respectively; EST and EMX measured 29.8 and 29.9, respectively. For the HF concentrations, 10% and 15% showed higher µSBS means than did 1% and 2.5% (p<0.05); 7.5% was higher than 1% (p<0.05); and no statistical differences were found among the other concentrations (p>0.05). When evaluating UR, µSBS mean was significantly higher and better infiltration was observed on the etched surfaces. No statistical difference was found between the ceramics. The HF concentration and UR influenced the bond strength and surface/interface morphology.

Association of single nucleotide polymorphisms in the gene encoding GLUT1 and diabetic nephropathy in Brazilian patients with type 1 diabetes mellitus.

Mesangial cells subject to high extracellular glucose concentrations, as occur in hyperglycaemic states, are unable to down regulate glucose influx, resulting in intracellular activation of deleterious biochemical pathways. A high expression of GLUT1 participates in the development of diabetic glomerulopathy. Variants in the gene encoding GLUT1 (SLC2A1) have been associated to this diabetic complication. The aim of this study was to test whether polymorphisms in SLC2A1 confer susceptibility to diabetic nephropathy (DN) in Brazilian type 1 diabetes patients. Four polymorphisms (rs3820589, rs1385129, rs841847 and rs841848) were genotyped in a Brazilian cohort comprised of 452 patients. A prospective analysis was performed in 155 patients. Mean duration of follow-up was 5.6 ± 2.4 years and the incidence of renal events was 18.0%. The rs3820589 presented an inverse association with the prevalence of incipient DN (OR: 0.36, 95% CI: 0.16 - 0.80, p=0.01) and with progression to renal events (HR: 0.20; 95% CI: 0.03 - 0.70; p=0.009). AGGT and AGAC haplotypes were associated with the prevalence of incipient DN and the AGAC haplotype was also associated with the prevalence of established/advanced DN. In conclusion, rs3820589 in the SLC2A1 gene modulates the risk to DN in Brazilian patients with inadequate type 1 diabetes control.

Reestablishing Biology, Function, and Esthetics for Fractured, Immature Incisors.

A seven-year-old boy with enamel-dentin fractures on both maxillary central incisors presented to the Piracicaba Dental School-UNICAMP seven days after the trauma. At the clinical evaluation, there were no clinical signs of pulp exposure, neither tooth was mobile, and both affected teeth presented a positive response to sensitivity tests and a negative response for percussion and palpation. The radiographic examination showed an undeveloped root and opened apex for both teeth. Indirect pulp capping was performed on the left maxillary central incisor, followed by a direct restoration. After one month, the patient complained of pain in the left central incisor, which responded negatively to sensitivity testing. Pulp revascularization was performed only on this tooth and was followed for 18 months. During this period, the left maxillary central incisor did not recover sensitivity, although radiographic examination showed apical closure, a slight increase in root length, and the formation of a mineralized barrier between the root canal and sealing material. The technique achieved its goal of restoring biological aspects, function, and esthetics of traumatized teeth when using this multidisciplinary approach.

Phenotype adaptability and stability of sugarcane genotypes in the sugarcane belt of the state of Pernambuco, Brazil.

We assessed the agroindustrial performance of 25 sugarcane genotypes adapted to the edaphoclimatic conditions of the State of Pernambuco, Brazil, within the microregions Mata Norte, Mata Sul, Região Central, Litoral Norte, and Litoral Sul. The variables analyzed were POL tonnage per hectare, sugarcane tonnage per hectare, fiber and total recoverable sugar tonnage per hectare, using a randomized block design with four repetitions. Combined variance of experiments, genetic parameter estimates, decomposition of the genotype-environment interaction, and environment stratification were analyzed. Phenotype adaptability and stability were also analyzed. The various genotypes presented great potential for improvement and a similar response pattern to the microregions Centro and Mata Sul of the state of Pernambuco. Genotypes RB863129, RB867515, RB92579, RB953180, SP81-3250, RB75126, and RB942520 were better in productivity and phenotype adaptability and stability compared to genotypes RB892700, RB943365, SP79-1011, Q138, RB943538, SP78-4764, RB953281, RB943066, RB928064, RB93509, RB72454, RB952675, RB952991, RB943161, RB942898, RB872552, RB952900, and RB942849. These genotypes are recommended as cultivation options in the sugarcane belt in the state of Pernambuco, since they stand out in terms of phenotype adaptability and stability as evaluated using the method by Annicchiarico, Lin and Bins, and the method by Eberhart and Russel.