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ES Bronze-Uhle,1 BC Costa,1 VF Ximenes,2 PN Lisboa-Filho1 1Department of Physics, São Paulo State University (Unesp), School of Sciences, Bauru, São Paulo, Brazil; 2Department of Chemistry, São Paulo State University (Unesp), School of Sciences, Bauru, São Paulo, Brazil Abstract: Bovine serum albumin (BSA) is highly water soluble and binds drugs or inorganic substances noncovalently for their effective delivery to various affected areas of the body. Due to the well-defined structure of the protein, containing charged amino acids, albumin nanoparticles (NPs) may allow electrostatic adsorption of negatively or positively charged molecules, such that substantial amounts of drug can be incorporated within the particle, due to different albumin-binding sites. During the synthesis procedure, pH changes significantly. This variation modifies the net charge on the surface of the protein, varying the size and behavior of NPs as the drug delivery system. In this study, the synthesis of BSA NPs, by a desolvation process, was studied with salicylic acid (SA) as the active agent. SA and salicylates are components of various plants and have been used for medication with anti-inflammatory, antibacterial, and antifungal properties. However, when administered orally to adults (usual dose provided by the manufacturer), there is 50% decomposition of salicylates. Thus, there has been a search for some time to develop new systems to improve the bioavailability of SA and salicylates in the human body. Taking this into account, during synthesis, the pH was varied (5.4, 7.4, and 9) to evaluate its influence on the size and release of SA of the formed NPs. The samples were analyzed using field-emission scanning electron microscopy, transmission electron microscopy, Fourier transform infrared, zeta potential, and dynamic light scattering. Through fluorescence, it was possible to analyze the release of SA in vitro in phosphate-buffered saline solution. The results of chemical morphology characterization and in vitro release studies indicated the potential use of these NPs as drug carriers in biological systems requiring a fast release of SA. Keywords: albumin nanoparticles, drug delivery, salicylic acid entrapped, nano-carriers

Background: The Woven EndoBridge (WEB) device is a minimally invasive endovascular treatment option for patients with cerebral aneurysms. Transradial access (TRA) is a technique that involves accessing the arterial system through the radial artery in the wrist rather than the femoral artery in the groin. Several studies have investigated the use of TRA for WEB device deployment in treating intracranial aneurysms., Methods: A systematic review was conducted to evaluate the TRA for WEB device deployment in treating intracranial aneurysms. The databases PubMed, Cochrane, Embase, Scopus, and Web of Science were searched. To reduce the risk of bias, this systematic review only included studies reporting on using TRA in WEB device deployment for intracranial aneurysm treatment with a minimum of four patients., Results: In this systematic review, 186 patients were included across five studies, with TRA used in 183 cases analyzed. The study population had a higher proportion of females ( n = 118%-69%) than males, with a mean age of 62 years old. Among the aneurysms treated, 46 were ruptured, and 119 were located at bifurcation sites, with a mean maximum diameter/width of 6.6 mm and mean height of 5.9 mm. Adjunctive coiling was used in three cases, and adjunctive stenting was used in nine cases. In two cases, conversion to a femoral artery access was necessary., Conclusion: The available results suggest TRA with the WEB device is a safe and effective alternative. However, using TRA versus TFA should be individualized based on patient factors and operator experience., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Develop a sustainable bovine hydroxyapatite dental ceramic with the addition of titanium dioxide (TiO 2 ) nanoparticles (5 % and 8 % by weight), analyzing the outcome of this addition to the microstructure, as well as its mechanical and chemical properties, in order to evaluate whether they satisfy the International Organization for Standardization (ISO) 6872:2015 for dental ceramics or not., Methods: Disks were obtained through uniaxial followed by isostatic pressing from bovine hydroxyapatite powder and TiO 2 nanoparticles and sintered at 1300ºC for 2 h. Three experimental groups were developed (HA, HA+5 %TiO 2 and HA+8 %TiO 2 ) and subjected to X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), indentation fracture (IF), biaxial flexural strength (BFS) and chemical solubility test., Results: XRD revealed, for HA group, the appearance of a peak corresponding to b-tricalcium phosphate (ß-TCP). For HA+ 5 %TiO 2 and HA+ 8 %TiO 2, the entire composition was converted into ß-TCP and calcium titanate (CaTiO 3 ). The SEM images showed a dense ceramic matrix and a uniform distribution of another phase in groups with TiO 2 nanoparticles. HA+ 5 %TiO 2 (1.40 ± 0.18 MPa.m 1/2 ) and HA+ 8 %TiO 2 (1.32 ± 0.18 MPa.m 1/2 ) showed significantly higher fracture toughness values than HA (0.67 ± 0.09 MPa.m 1/2 ). HA showed significantly higher characteristic stress (295.8 MPa) in comparison to groups with 5 % (235.1 MPa) and 8 % (214.4 MPa) TiO 2 nanoparticles. Differences were not observed between the Weibull modulus values. The solubility results indicated that all experimental ceramics were above the 2000 ug/cm 2 limit set by the ISO 6872:2015., Significance: This study proposed the development and characterization of a new ceramic for dental prosthesis made from HA extracted from bovine bones, with the intention of reusing these solids waste and transforming them into a sustainable and low-cost material. Although the experimental calcium phosphate ceramic with additions of 5 % and 8 % of TiO 2 achieved desirable mechanical properties, the chemical solubility values were very high., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Bisphosphonates are widely used for the treatment of postmenopausal osteoporosis; however, they cause several long-term side effects, necessitating the investigation of local ways to improve osseointegration in compromised bone tissue. The purpose of this study was to evaluate peri-implant bone repair using implants functionalized with zoledronic acid alone (OVX ZOL group, n = 11), zoledronic acid + teriparatide (OVX ZOL + TERI group, n = 11), and zoledronic acid + ruterpy (OVX ZOL + TERPY group, n = 11) compared to the control group (OVX CONV, n = 11). Analyses included computer-assisted microtomography, qualitative histologic analysis, and real-time PCR analysis. Histologically, all functionalized surfaces improved peri-implant repair, with the OVX ZOL + TERI group standing out. Similar results were found in computerized microtomography analysis. In real-time PCR analysis, however, the OVX ZOL and OVX ZOL + TERPY groups showed better results for bone formation, with the OVX ZOL + TERPY group standing out, while there were no statistical differences between the OVX CONV and OVX ZOL + TERI groups for the genes studied at 28 postoperative days. Nevertheless, all functionalized groups showed a reduced rate of bone resorption. In short, all surface functionalization groups outperformed the control group, with overall better results for the OVX ZOL + TERI group.

This study aimed to produces and characterize bovine hydroxyapatite (HA) bioceramic with 3Y-TZP addition and analyze different sintering curves. HA was extracted from bovine bones and nanoparticulated. HA discs (0, 1, 5 and 10 wt% 3Y-TZP) were subjected to uniaxial and isostatic pressing. Dilatometry analysis was performed and the groups were sintered using 3 different firing curves (conventional, 1300 °C; 2-step, 1292 °C; 2-step, 1420 °C). The samples were analyzed by X-ray diffraction (XRD), biaxial flexural strength (BFS), Vickers microhardness (VH) and Field emission scanning electron microscopy (FE-SEM). The dilatometry results signaled the need for sintering optimization in groups added with 3Y-TZP. XRD demonstrated the characteristic crystallographic peaks of HA in the pure groups and with 1% 3Y-TZP, and decomposition of HA into β-TCP and formation of calcium zirconate in the groups with 5 and 10% 3Y-TZP. Considering each composition, the groups of pure HA (131.3 ± 13.5 MPa; 401 ± 12.7 GPa) sintered by the conventional curve and HA+1%3Y-TZP (145 ± 8.6 MPa; 507 ± 47.9 GPa), HA+5%3Y-TZP (68.1 ± 14.2 MPa; 183 ± 9.8 GPa) and HA+10%3Y-TZP (55.6 ± 5.1 MPa; 96.1 ± 7.64 GPa) sintered by the 2-step curve at 1420 °C, combined the best BFS and VH results. The addition of 1 wt% 3Y-TZP and optimization in the sintering process improved the mechanical and microstructural properties of HA bioceramics and maintenance of its crystalline characteristics. Refinement in material processing is necessary for the future use of this bioceramic in dentistry., 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 © 2024 Elsevier Ltd. All rights reserved.)

Coating high-touch surfaces with inorganic agents, such as metals, appears to be a promising long-term disinfection strategy. However, there is a lack of studies exploring the effectiveness of copper-based products against viruses. In this study, we evaluated the cytotoxicity and virucidal effectiveness of products and materials containing copper against mouse hepatitis virus (MHV-3), a surrogate model for SARS-CoV-2. The results demonstrate that pure CuO and Cu possess activity against the enveloped virus at very low concentrations, ranging from 0.001 to 0.1% (w/v). A greater virucidal efficacy of CuO was found for nanoparticles, which showed activity even against viruses that are more resistant to disinfection such as feline calicivirus (FCV). Most of the evaluated products, with concentrations of Cu or CuO between 0.003 and 15% (w/v), were effective against MHV-3. Cryomicroscopy images of an MHV-3 sample exposed to a CuO-containing surface showed extensive damage to the viral capsid, presumably due to the direct or indirect action of copper ions., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

To evaluate the microstructural characterization, mechanical properties and antimicrobial activity of acrylic resins incorporated with different concentrations of reduced graphene oxide (rGO). Specimens were made of self-cured and heat-cured acrylic resins for the control group and concentrations of 0.5%, 1%, and 3%. The microstructural characterization was evaluated by scanning electron microscopy (SEM) and energy-dispersive X-ray (EDS). For mechanical testing, flexural strength, and Knoop hardness tests were performed. Microbiological evaluations were performed by colony forming units (CFU) analysis, tetrazolium salt reduction (XTT), and SEM images. The modified acrylic resins showed increased mechanical properties at low concentrations (p < 0.05) and with reduced S. mutans (p < 0.05). Reduced graphene oxide interfered with the mechanical performance and microbiological properties of acrylic resins depending on the concentration of rGO, and type of polymerization and microorganism evaluated. The incorporation of graphene compounds into acrylic resins is an alternative to improve the antimicrobial efficacy and performance of the material., (© 2024. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

This study aimed to incorporate β-AgVO 3 and rGO into self-curing (SC) and heat-curing (HC) acrylic resins and to evaluate their physicochemical, mechanical, and antimicrobial properties while correlating them with the characterized material structure. Acrylic resin samples were prepared at 0 % (control), 0.5 %, 1 %, and 3 % for both nanoparticles. The microstructural characterization was assessed by scanning electron microscopy (SEM) (n = 1) and energy dispersive X-ray spectroscopy (EDS) (n = 1). The physicochemical and mechanical tests included flexural strength (n = 10), Knoop hardness (n = 10), roughness (n = 10), wettability (n = 10), sorption (n = 10), solubility (n = 10), porosity (n = 10), and color evaluation (n = 10). The microbiological evaluation was performed by counting colony-forming units (CFU/mL) and cell viability (n = 8). The results showed that the β-AgVO 3 samples showed lower counts of Candida albicans , Pseudomonas aeruginosa , and Streptococcus mutans due to their promising physicochemical properties. The mechanical properties were maintained with the addition of β-AgVO 3 . The rGO samples showed higher counts of microorganisms due to the increase in physicochemical properties. It can be concluded that the incorporation of β-AgVO 3 into acrylic resins could be an alternative to improve the antimicrobial efficacy and performance of the material., Competing Interests: 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., (© 2024 Published by Elsevier Ltd.)

Objectives: To assess the impact of different concentrations TiO 2 -nt incorporated into a glass ionomer cement on the proliferation, mitochondrial metabolism, morphology, and pro- and anti-inflammatory cytokine production of cultured fibroblasts (NIH/3T3), whether or not stimulated by lipopolysaccharides (LPS-2 μg/mL, 24 h)., Methods: TiO 2 -nt was added to KM (Ketac Molar EasyMix™, 3 %, 5 %, 7 % in weight); unblended KM was used as the control. The analyses included: Cell proliferation assay (n = 6; 24/48/72h); Mitochondrial metabolism assay (n = 6; 24/48/72h); Confocal laser microscopy (n = 3; 24/48/72h); Determination of biomarkers (IL-1β/IL-6/IL-10/VEGF/TNF) by using both multiplex technology (n = 6; 12/18 h) and the quantitative real-time PCR assay (q-PCR) (n = 3, 24/72/120 h). The data underwent analysis using both the Shapiro-Wilk and Levene tests, and by generalized linear models (α = 0.05)., Results: It demonstrated that cell proliferation increased over time, regardless of the presence of TiO 2 -nt or LPS, and displayed a significant increase at 72 h; mitochondrial metabolism increased (p < 0.05), irrespective of exposure to LPS (p = 0.937); no cell morphology changes were observed; TiO 2 -nt reverted the impact of KM on the secreted levels of the evaluated proteins and the gene expressions in the presence of LPS (p < 0.0001)., Conclusions: TiO 2 -nt did not adversely affect the biological behavior of fibroblastic cells cultured on GIC discs., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Kamila Rosamilia Kantovitz reports financial support was provided by State of Sao Paulo Research Foundation. Pedro Viel Gogolla reports was provided by State of Sao Paulo Research Foundation. Joao Pedro Coelho Rangel reports financial support was provided by State of Sao Paulo Research Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Titanium (Ti) is widely utilized as an implant material; nonetheless, its integration with bone tissue faces limitations due to a patient's comorbidities. To address this challenge, we employed a strategic approach involving the growth of thin films by spin-coating and surface functionalization with etidronate (ETI), alendronate (ALE), and risedronate (RIS). Our methodology involved coating of Ti cp IV disks with thin films of TiO2, hydroxyapatite (HA), and their combinations (1:1 and 1:2 v/v), followed by surface functionalization with ETI, ALE, and RIS. Bisphosphonate-doped films were evaluated in terms of surface morphology and physical-chemical properties by techniques such as electron microscopy, confocal microscopy, and x-ray photoelectron spectroscopy. The antibacterial potential of bisphosphonates alone or functionalized onto the Ti surface was tested against Staphylococcus aureus biofilms. Primary human bone mesenchymal stem cells were used to determine in vitro cell metabolism and mineralization. Although RIS alone did not demonstrate any antibacterial effect as verified by minimum inhibitory concentration assay, when Ti surfaces were functionalized with RIS, partial inhibition of Staphylococcus aureus growth was noted, probably because of the physical-chemical surface properties. Furthermore, samples comprising TiO2/HA (1:1 and 1:2 v/v) showcased an enhancement in the metabolism of nondifferentiated cells and can potentially enhance the differentiation of osteoblastic precursors. All samples demonstrated cell viability higher than 80%. Addition of hydroxyapatite and presence of bisphosphonates increase the metabolic activity and the mineralization of human bone mesenchymal cells. While these findings hold promise, it is necessary to conduct further studies to evaluate the system's performance in vivo and ensure its long-term safety. This research marks a significant stride toward optimizing the efficacy of titanium implants through tailored surface modifications., (2024 Published under an exclusive license by the AVS.)

Objectives: This study evaluated the influence of hydrogen peroxide (HP) with or without titanium dioxide nanotubes (TiO2) associated with violet LED (VL) regarding: a) the temperature change in the pulp chamber and facial surface; b) the decomposition of HP; and c) the cytotoxicity of the gels on pulp cells., Methods and Materials: The experimental groups were: HP35 (35% HP/Whiteness HP, FGM); HP35+VL; HP35T (HP35+TiO2); HP35T+VL; HP7 (7.5% HP/White Class 7.5%, FGM); HP7+VL; HP7T (HP7+TiO2); and HP7T+VL. TiO2 was incorporated into the bleaching gels at 1%. Eighty bovine incisors were evaluated to determine temperature change in 8 experimental groups (n=10/group). A k-type thermocouple was used to evaluate the temperatures of the facial surface and in the pulp chamber, achieved by enabling endodontic access to the palatal surface, throughout the 30-minute session. HP decomposition (n=3) of gels was evaluated by using an automatic potentiometric titrator at the initial and 30-minute time points. Trans-enamel and trans-dentinal cell viability were assessed with a pulp chamber device as well as enamel and dentin discs (n=6), and the treatment extracts (culture medium + diffused components) were collected and applied to MDPC-23 odontoblast cells to evaluate cell viability according to the MTT test., Results: A temperature increase in the pulp chamber was observed in the presence of VL at 30 minutes (p<0.05) (Mann-Whitney test). Also at 30 minutes, HP35 showed greater decomposition in the presence of VL rather than in its absence (p<0.05) (mixed linear models and the Tukey-Kramer test). HP7 provided greater cell viability than the groups treated with HP35 (p<0.05) (generalized linear models test). Cell viability was significantly lower for HP7 in the presence of VL (p<0.05)., Conclusion: Pulpal temperature increased with VL (maximum of 1.9°C), but did not exceed the critical limit to cause pulp damage. Less concentrated HP resulted in higher cell viability, even when associated with VL., (©Operative Dentistry, 2024.)

Advances in methodologies to evaluate biomaterials brought an explosive growth of data, ensuing computational challenges to better analyzing them and allowing for high-throughput profiling of biological systems cost-efficiently. In this sense, we have applied bioinformatics tools to better understand the biological effect of different sintering temperatures of hydroxyapatite (abbreviated HA; at 1100, 1150, and 1250°C) on osteoblast performance. To do, we have better analyzed an earlier deposited study, in which the access code is E-MTAB-7219, which the authors have explored different in silico tools on this purpose. In this study, differential gene expression analyses were performed using the gene set variation analysis (GSVA) algorithm from the transcriptomes respecting the thermal changes of HA, which were validated using exclusively in vitro strategies. Furthermore, in silico approaches elected biomarkers during cell behavior in response to different sintering temperatures of HA, and it was further validated using cell culture and qPCR technologies. Altogether, the combination of those strategies shows the capacity of sintered HA at 1250°C to present a better performance in organizing an adequate microenvironment favoring bone regeneration, angiogenesis and material resorption stimulus once it has promoted higher involvement of genes such as CDK2, CDK4 (biomarkers of cell proliferation), p15, Osterix gene (related with osteogenic differentiation), RANKL (related with osteoclastogenesis), VEGF gene (related with angiogenesis), and HIF1α (related with hypoxia microenvironment). Altogether, the combination of in silico and cell culture strategies shows the capacity of sintered HA at 1250°C in guaranteeing osteoblast differentiation and it can be related in organizing an adequate microenvironment favoring bone regeneration, angiogenesis, and material resorption stimulus., (© 2024 Wiley Periodicals LLC.)

Introduction: Intracranial mycotic or infectious aneurysms result from the infection of arterial walls, most caused by bacterial or fungal organisms. These infections can weaken the arterial wall, leading to the formation of an aneurysm, a localized dilation, or a bulge. The management can be conservative mainly based on antibiotics or invasive methods such as clipping or endovascular treatment., Purpose: We performed a systematic review and meta-analysis of the current literature on endovascular treatment of mycotic aneurysms, analyzing the safety and efficacy associated with this procedure., Methods: We systematically searched on PUBMED, Cochrane Library, Embase, and Web of Science databases. Our search strategy was carefully crafted to conduct a thorough investigation of the topic, utilizing a comprehensive combination of relevant keywords. This meta-analysis included all studies that reported endovascular treatment of mycotic aneurysms. To minimize the risk of bias, studies with fewer than four patients, studies where the main outcome was not found, and studies with no clear differentiation between microsurgical and endovascular treatment were excluded., Results: In a comprehensive analysis of 134 patients, it was observed that all except one patient received antibiotics as part of their treatment. Among the patients, 56% (a total of 51 out of 90 patients) underwent cardiac surgery. Additionally, three patients required a craniotomy following endovascular treatment. 12 patients experienced morbidity related to the procedures performed, indicating complications arising from the interventions. Furthermore, four aneurysms experienced rebleeding while treatment. A pooled analysis of the endovascular treatment of the mycotic aneurysm revealed a good level of technical success, achieving a 100% success rate in 12 out of 14 studies (97-100%; CI 95%; I 2 = 0%), as illustrated in Fig. 2. Similarly, the aneurysm occlusion rate demonstrated a notable efficacy, with a success rate of 97% observed in 12 out of 14 studies (97-100%; CI 95%; I 2 = 0%), as depicted in Fig. 3., Conclusion: The results strongly support the efficacy of endovascular treatment in achieving technical success, complete aneurysm occlusion, and favorable neurological outcomes. Additionally, the notably low incidence of complications and procedure-related mortality reaffirms the safety and benefits associated with this intervention., Competing Interests: Declaration of Competing Interest The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The effectiveness of dental color change was assessed by incorporating titanium dioxide (TiO 2 ) into 37% carbamide peroxide bleaching agent associated with hybrid light., Methodology: Fifty bovine incisors were selected to receive the bleaching treatment, and separated into five groups (n = 10): 35% hydrogen peroxide (HP) (Whiteness HP, FGM/HP); 37% carbamide peroxide (CP) (Whiteness SuperEndo, FGM/CP); CP + hybrid light (HL) (CP HL); CP + 1% TiO 2 (CP TiO 2 ); CP TiO 2  + hybrid light (CP TiO 2 HL). The bleaching gels were applied to the dental surface for 30 min. Hybrid light (Whitening Plus, DMC/infrared laser diodes + blue LEDs +violet LEDs) was applied with 1 min of active light, alternating with 1 min of pause. A spectrophotometer (VITA Easyshade® Advance, Vita) was used to determine the color of the dental elements at baseline and time points after the 1st, 2nd and 3rd bleaching sessions. Color change effectiveness was evaluated using Vita Classical, CIEL*a*b*, WI D and ΔE ab , ΔE 00 and ΔWI D parameters., Results: Generalized mixed linear models for repeated measures (α = 5%) showed significant decrease in Vita Classical scores and a* and b* values, as well as an increase in L* and ∆W ID values for all the groups. Higher color change values for ΔE ab were observed for CP HL and CP TiO 2 HL, while those of ΔE 00 and ΔWI D were higher for CP TiO 2 HL at the end of the bleaching treatment., Conclusion: Hybrid light applied with TiO 2 incorporated into CP potentiated the effectiveness of the color change in the tooth structure ., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

Postmenopausal osteoporosis and poor dietary habits can lead to overweightness and obesity. Bisphosphonates are the first-line treatment for osteoporosis. However, some studies show that they may increase the risk of osteonecrosis of the jaw. Considering the antimicrobial, angiogenic and vasodilatory potential of nitric oxide, this study aims to evaluate the local activity of this substance during the placement of surface-treated implants. Seventy-two Wistar rats were divided into three groups: SHAM (SHAM surgery), OVX + HD (ovariectomy + cafeteria diet), and OVX + HD + RIS (ovariectomy + cafeteria diet + sodium risedronate treatment), which were further subdivided according to the surface treatment of the future implant: CONV (conventional), TE10, or TE100 (TERPY at 10 or 100 μM concentration); n = 8 per subgroup. The animals underwent surgery for implant installation in the proximal tibia metaphysis and were euthanized after 28 days. Data obtained from removal torque and RT-PCR (OPG, RANKL, ALP, IBSP and VEGF expression) were subjected to statistical analysis at 5% significance level. For biomechanical analysis, TE10 produced better results in the OVX + HD group (7.4 N/cm, SD = 0.6819). Molecular analysis showed: (1) significant increase in OPG gene expression in OVX groups with TE10; (2) decreased RANKL expression in OVX + HD + RIS compared to OVX + HD; (3) significantly increased expressions of IBSP and VEGF for OVX + HD + RIS TE10. At its lowest concentration, TERPY has the potential to improve peri-implant conditions.

This study characterized TiO 2 nanotube (TiO 2 -nt) ultrastructure and morphology, and the physicochemical impact on high-viscosity conventional glass-ionomer cement (GIC). TiO 2 -nt was synthesized by the alkaline method (n = 3), assessed by scanning (SEM) and transmission electron microscope (TEM), and was added (3%, 5%, 7%-in weight) to KM (Ketac Molar EasyMix™). Analyses included: SEM; Energy-dispersive spectroscopy (EDS); Raman spectroscopy (RAMAN); Setting time with Gillmore needles (ST); Color (Co); Radiopacity (XR); Water sorption (WS); and solubility (SO). Quantitative data were submitted to ANOVA and Tukey's tests (chr = 0.05). External and internal TiO 2 -nt diameters were 11 ± 2 nm and 6 ± 0 nm, respectively. Data analyses showed: (i) TiO 2 -nt present into KM matrix, with a concentration-dependent increase of Ti levels into KM, (ii) physical interaction between KM and TiO 2 -nt, (iii) longer initial ST for the 7% group compared to KM and 3% groups (p ≤ 0.01), (iv) decreased luminosity and yellowness for the 5% and 7% groups, (v) 36% greater radiopacity for the 5% group compared to enamel, dentin, and KM, and (vi) lower SO values for the 5% group, with no significant differences on WS across the groups. TiO 2 -nt displayed physical interaction with KM matrix, and also modified SO, XR and Co, without affecting ST. This study provides information on the potential impact of TiO 2 -nt on GIC performance. TiO 2 -nt may be proposed to boost confidence among dental surgeons in terms of GIC's handling characteristics, success rate and differential diagnostic., (© 2023. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

Hypertension and estrogen deficiency can affect bone metabolism and therefore increase the risk of osseointegration. Antihypertensive drugs such as losartan not only control blood pressure but also enhance bone healing. In addition, alendronate sodium is widely used to treat postmenopausal osteoporosis. Hence, we evaluated the effect of systemic antihypertensive and local alendronate coted on implants on osseointegration under hypertensive and estrogen-deficiency conditions. A total of 64 spontaneously hypertensive rats (SHRs) treated with losartan were randomly divided according to the estrogen-deficiency induction by ovariectomy (OVX) or not (SHAM), and whether the implant surface was coated with sodium alendronate (ALE) or not, resulting in four groups: SHR SHAM, SHR SHAM ALE, SHR OVX, and SHR OVX ALE. The removal torque, microcomputed tomography, and epifluorescence microscopy were the adopted analyses. The hypertensive and estrogen-deficiency animals presented a lower removal torque even when treated with alendronate on implant surface. The microcomputed tomography revealed a higher bone volume and bone-to-implant contact in the SHRs than the SHR OVX rats. Epifluorescence showed a decreased mineral apposition ratio in the SHR OVX ALE group. The data presented indicate that estrogen deficiency impairs osseointegration in hypertensive rats; in addition, alendronate coated on the implant surface does not fully reverse this impaired condition caused by estrogen deficiency.

Hydroxyapatite (HA) from bovine bones has been used as a biomaterial in dentistry due to its biocompatibility and bioactivity. However, dense HA bioceramics still present inadequate properties for applications that require high mechanical performance, such as infrastructure. Microstructural reinforcements and control of ceramic processing steps are methods to improve these shortcomings. The present study assessed the effects of polyvinyl butyral (PVB) addition in combination with two sintering methodologies (2-step and conventional), on the mechanical properties of polycrystalline bovine HA bioceramics. The samples were divided into four groups (with 15 samples per group): conventional sintering with binder (HBC) and without binder (HWC) and 2-step sintering with (HB2) and without binder (HW2). HA was extracted from bovine bones, turned into nanoparticles in a ball mill, and subjected to uniaxial and isostatic pressing into discs, according to ISO 6872 standards. All groups were characterized by x-ray diffractometry (XRD), differential thermal analysis (DTA) and Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and relative density. Besides, mechanical analyses (biaxial flexural strength (BFS) and modulus of elasticity) were also performed. The characterization results demonstrated that adding agglutinants or the sintering method did not affect HA's chemical and structural characteristics. Even so, the HWC group showed the highest mechanical values for BFS and modulus of elasticity being 109.0 (98.0; 117.0) MPa and 105.17 ± 14.65 GPa, respectively. The HA ceramics submitted to conventional sintering and without the addition of binders achieved better mechanical properties than the other groups. The impacts of each variable were discussed and correlated to the final microstructures and mechanical properties., 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 © 2023 Elsevier Ltd. All rights reserved.)

The imbalance in the concentration of metallic nanoparticles has been demonstrated to play an important role in multiple sclerosis (MS), which may impact cognition. Biomarkers are needed to provide insights into the pathogenesis and diagnosis of MS. They can be used to gain a better understanding of cognitive decline in people with MS (pwMS). In this study, we investigated the relationship between the blood concentration of metallic nanoparticles (blood nanoparticles) and cognitive performance in pwMS. First, four mL blood samples, clinical characteristics, and cognitive performance were obtained from 21 pwMS. All participants had relapse-remitting MS, with a score of ≤4.5 points in the expanded disability status scale. They were relapse-free in the three previous months from the day of collection and had no orthopedic, muscular, cardiac, and cerebellar diseases. We quantified the following metallic nanoparticles: aluminum, chromium, copper, iron, magnesium, nickel, zinc, and total concentration. Cognitive performance was measured by mini-mental state examination (MMSE) and the symbol digit modalities test (SDMT). Pearson's and Spearman's correlation coefficients and stepwise linear regression were calculated to assess the relationship between cognitive performance and blood nanoparticles. We found that better performance in SDMT and MMSE was related to higher total blood nanoparticles (r = 0.40; p < 0.05). Also, better performance in cognitive processing speed and attention (SDMT) and mental state (MMSE) were related to higher blood iron (r = 0.44; p < 0.03) and zinc concentrations (r = 0.41; p < 0.05), respectively. The other metallic nanoparticles (aluminum, chromium, copper, magnesium, and nickel) did not show a significant relationship with the cognitive parameters ( p > 0.05). Linear regression estimated a significant association between blood iron concentration and SDMT performance. In conclusion, blood nanoparticles are related to cognitive performance in pwMS. Our findings suggest that the blood concentration of metallic nanoparticles, particularly the iron concentration, is a promising biomarker for monitoring cognitive impairment in pwMS.

Single-axis knee prosthesis is an artificial biomechanical device that provides motion to amputees without the need for assistance appliances. Besides it is mainly composed of metallic materials, the current commercial materials did not group adequate properties for long-term usage or accessible cost. This study produced and characterized Ti-(10 -x)Al-xV (x = 0, 2, and 4 wt.%) alloys for potential use as single-axis knee prostheses. The samples exhibited a gradual decrease in the density values, with proper chemical mixing of the alloying elements on the micro-scale. The phase composition exhibited a primary α phase with a minor α' + β phase for the Ti-8Al-2V and Ti-6Al-4V samples. Due to their different atomic radius compared to Ti, the addition of alloying elements changed the cell parameters. Their selected mechanical properties (Young's modulus, Vickers microhardness, and damping factor) performed better values than the CP-Ti grade 4. The samples also exhibited good corrosion properties against the simulated marine solution. The tribocorrosion resistance of the samples was better than the reference material, with the wear tracks composed of some tribolayers and grooves resulting from adhesive and abrasive wear. The Ti-10Al alloy displayed the best properties and estimated low cost to be used as single-axis knee prostheses., (© 2023. The Author(s).)

Background: The purpose of this study was: 1) to analyze the physical-chemical properties of hydrogen peroxide (HP) agents at 7.5% (HP7) and 35% (HP35), and the association with or without TiO 2 nanotubes; 2) to evaluate dental bleaching effectiveness by using HP7 and HP35 together with or without TiO 2 nanotubes, and applied with or without violet LED (VL)., Methodology: 80 bovine incisors were treated according to groups (n = 10): HP35; HP35 + VL; HP35T (HP35 + TiO 2 ); HP35T + VL; HP7; HP7 + VL; HP7T (HP7 + TiO 2 ); HP7T + VL. Bleaching effectiveness was measured at 4 time points according to the Vita Classical, CIEL*a*b*, CIEDE2000, and WI D parameters. HP35, HP35T, HP7, and HP7T were evaluated for mass change, pH, mean particle size (P), polydispersity (PDI), and zeta potential (ZP), over 6 months of storage., Results: The pH of HP35 thickener was higher when associated to TiO 2 . At baseline, both of the bleaching gels containing TiO 2 had lower P, PDI, and PZ (p < 0.05). All groups showed a significant decrease in Vita Classical color scores (p = 0.0037). There was a higher L* value, and lower b* values for HP7 when associated to VL after the 3rd session. (p < 0.05). HP35T showed higher color change (ΔE ab , ΔE 00 ), and lower a* value in the presence of VL (p < 0.05). ΔWI D presented lower values for both gels, when TiO 2 was incorporated (p ≤ 0.05)., Conclusion: The incorporation of TiO 2 to the bleaching gel showed good stability with minimal variations in physical-chemical properties. The color change in HP35 was more effective than in HP7, but the VL boosted the bleaching effectiveness of HP7, whereas TiO 2 did not increase bleaching effectiveness., Competing Interests: Declarations of Competing Interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

It is crucial for clinical needs to develop novel titanium alloys feasible for long-term use as orthopedic and dental prostheses to prevent adverse implications and further expensive procedures. The primary purpose of this research was to investigate the corrosion and tribocorrosion behavior in the phosphate buffered saline (PBS) of two recently developed titanium alloys, Ti-15Zr and Ti-15Zr-5Mo (wt.%) and compare them with the commercially pure titanium grade 4 (CP-Ti G4). Density, XRF, XRD, OM, SEM, and Vickers microhardness analyses were conducted to give details about the phase composition and the mechanical properties. Additionally, electrochemical impedance spectroscopy was used to supplement the corrosion studies, while confocal microscopy and SEM imaging of the wear track were used to evaluate the tribocorrosion mechanisms. As a result, the Ti-15Zr (α + α' phase) and Ti-15Zr-5Mo (α″ + β phase) samples exhibited advantageous properties compared to CP-Ti G4 in the electrochemical and tribocorrosion tests. Moreover, a better recovery capacity of the passive oxide layer was observed in the studied alloys. These results open new horizons for biomedical applications of Ti-Zr-Mo alloys, such as dental and orthopedical prostheses.

With the increase in the population's life expectancy, there has also been an increase in the rate of osteoporosis, which has expanded the search for strategies to regenerate bone tissue. The ultrasonic sonochemical technique was chosen for the functionalization of the 45S5 bioglass. The samples after the sonochemical process were divided into (a) functionalized bioglass (BG) and (b) functionalized bioglass with 10% teriparatide (BGT). Isolated mesenchymal cells (hMSC) from femurs of ovariectomized rats were differentiated into osteoblasts and submitted to in vitro tests. Bilateral ovariectomy (OVX) and sham ovariectomy (Sham) surgeries were performed in fifty-five female Wistar rats. After a period of 60 days, critical bone defects of 5.0 mm were created in the calvaria of these animals. For biomechanical evaluation, critical bone defects of 3.0 mm were performed in the tibias of some of these rats. The groups were divided into the clot (control) group, the BG group, and the BGT group. After the sonochemical process, the samples showed modified chemical topographic and morphological characteristics, indicating that the surface was chemically altered by the functionalization of the particles. The cell environment was conducive to cell adhesion and differentiation, and the BG and BGT groups did not show cytotoxicity. In addition, the experimental groups exhibited characteristics of new bone formation with the presence of bone tissue in both periods, with the BGT group and the OVX group statistically differing from the other groups ( p < 0.05) in both periods. Local treatment with the drug teriparatide in ovariectomized animals promoted positive effects on bone tissue, and longitudinal studies should be carried out to provide additional information on the biological performance of the mutual action between the bioglass and the release of the drug teriparatide.

Objectives: This study evaluated the effect of TiO 2 nanoparticles + dense hydroxyapatite (HA) on human osteoblast cells (SAOS-2)., Methods: Particulate bovine HA powder with or without the addition of either 5 or 8 % TiO 2 (HA, HA/TiO 2 Np5 % or HA/TiO 2 Np8 %) were pressed into disks (Ø = 12.5 mm; thickness = 1.3 mm) uniaxially (100 MPa) and isostatically (200 MPa/1 min) and sintered at 1300 °C. Y-TZP disks were used as control. The following tests were performed: Scanning Electron Microscopy and Dispersive Energy Spectroscopy (SEM/EDS), Atomic Force Microscopy (AFM), cell viability assay (Alamar Blue-AB) and mineralized matrix deposition (Alizarin Red-AR). AB and AR data were submitted to 2-way ANOVA/Tukey tests and ANOVA/Tukey tests, respectively., Results: SEM revealed that the surface of HA/TiO 2 Np5% resembles DPBHA surface, but also contains smaller granules. HA/TiO 2 Np8% characteristics resembles HA/TiO 2 Np5% surface, but with irregular topography. Y-TZP showed a typical oxide ceramic surface pattern. EDS revealed Ca, O, and P in all samples. C, O, and Zr appeared in Y-TZP samples. AFM data corroborates SEM analysis. AB test revealed excellent cellular viability for HA/TiO 2 Np5% group. AR test showed that all groups containing TiO 2 np had more mineralized matrix deposition than all other groups, with statistically differences between HA/TiO 2 Np8% and HA cultivated in non-osteogenic medium. Culture in osteogenic medium exhibited much more mineralized matrix deposition by TiO 2 np groups., Significance: In conclusion, the addition of TiO 2 np showed chemical, superficial, and biological changes in the reinforced materials. HA/TiO 2 Np5% showed the best results for cell viability and HA/TiO 2 Np8% for mineralized matrix deposition., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: This study evaluated the microshear bond strength of a resin cement to Y-TZP after different methods of TiO 2 nanotubes (nTiO 2 ) incorporation on pre-sintered Y-TZP surfaces., Methods: nTiO 2 were synthesized and incorporated on Y-TZP slices as follows (n = 15): 1) nTiO 2 mixed with isopropyl alcohol/manual application (MAl); 2) nTiO 2 mixed with acetone/manual application (MAc); 3) nTiO 2 mixed with isopropyl alcohol/high-pressure vacuum application (HPVAl); 4) nTiO 2 mixed with acetone/high-pressure vacuum application (HPVAc). As controls, surfaces were sandblasted with Al 2 O 3 (OX) or Rocatec silicatization (ROC). All ceramics were sintered after nTiO 2 incorporation. Surface treatments of OX and ROC were made after sintering. Surfaces were characterized by confocal laser microscopy, scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). Resin composite cylinders (1.40 mm diameter and 1 mm height) were cemented with a resin cement, stored in water at 37 °C for 24 h and thermocycled for 10 000 cycles before microshear bond strength evaluation. Data were analyzed with one-way ANOVA and Games-Howell (α = 0.05), and fracture analysis was performed using a stereomicroscope., Results: EDS confirmed the presence of TiO 2 on treated Y-TZP. The confocal analysis showed higher roughness for HPVAc and OX. There were significant differences between surface treatments (p < 0.001). HPVAl (22.96 ± 10.3), OX (34.16 ± 7.9) and ROC (27.71 ± 9.4) showed higher microshear bond strengths and were statistically similar (p > 0.05). MAC showed intermediary values, and HPVAc and MAl presented decreased bond strength, with a high percentage of premature debonding., Conclusion: High-pressure vacuum application of nTiO 2 mixed with isopropyl alcohol was able to produce bond strength values compared to conventional air abrasion and Rocatec silicatization., Significance: The infiltration of TiO 2 nanostructures on the pre-sintered Y-TZP is an interesting approach that can improve bond strength without the need of sandblasting methods., (Copyright © 2022 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

Titanium dioxide nanotubes (TiO2-nts) were incorporated into a glass ionomer cement (GIC) with improved mechanical properties and antibacterial activity. The aims of the present in vitro study were to define the elemental characterization, aluminum (Al) release rate, and initial working time for GIC reinforced with TiO2-nts, in an experimental caries model. TiO2-nts were incorporated into GIC powder components at 5% by weight, and compared with unblended GIC. Experimental approaches used energy-dispersive spectrometry (EDS), atomic absorption spectrophotometry (AAS), and brightness loss to define surface element properties, Al release rates, and initial working time, respectively. Statistical analysis was performed by 2-way ANOVA, Tukey's test, generalized linear models, and Student's t test (a = 0.05). EDS data analysis revealed that TiO2-nts incorporated into GIC had no significant impact on the typical elemental composition of GICs in an in vitro caries model. Regarding the demineralizing solution, GIC with TiO2-nt significantly decreased the Al release rate, compared with the control group (p < 0.0001). Moreover, TiO2-nt incorporated into GIC did not alter the initial working time of the material (p > 0.05). These findings add information to our scientific body of knowledge concerning the potential impact of TiO2-nt on the performance of conventional GICs.

Surface hydroxylation has been extensively studied over the years for a variety of applications, and studies involving hydroxylation of different silica surfaces are still carried out due to the interesting properties obtained from those modified surfaces. Although a number of theoretical studies have been employed to evaluate details on the hydroxylation phenomenon on silica (SiO 2 ) surfaces, most of these studies are based on computationally expensive models commonly based on extended systems. In order to circumvent such an aspect, here we present a low-cost theoretical study on the SiO 2 hydroxylation process aiming to evaluate aspects associated with water-SiO 2 interaction. Details about local reactivity, chemical softness, and electrostatic potential were evaluated for SiO 2 model substrates in the framework of the density functional theory (DFT) using a molecular approach. The obtained results from this new and promising approach were validated and complemented by fully atomistic reactive molecular dynamics (FARMD) simulations. Furthermore, the implemented approach proves to be a powerful tool that is not restricted to the study of hydroxylation, opening a promising route for low computational cost to analyze passivation and anchoring processes on a variety of oxide surfaces., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The objective of this work was to investigate the use of Biogran® functionalized with parathyroid hormone (PTH) 1-34 by sonochemistry for the local delivery of this anabolic agent to the implant site. The effects of Biogran® and topical administration of PTH 1-34 on peri-implant bone regeneration were evaluated from the microscale to ultrastructural levels in healthy (SHAM) and orchiectomized (ORQ). While some animals only received a titanium implant in their tibial metaphyses (CLOT group), in others the peri-implant defect was first filled with Biogran® either without or with PTH 1-34 functionalization (BG and BGPTH groups, respectively) prior to implant installation. Osseointegration was characterized from a biomechanical perspective by measuring the removal torque with the counter-torque technique. Micro-CT was used to evaluate the percentage of bone volume, trabecular thickness, number and separation, and bone-implant contact (BIC). Dynamics of new bone formation were assessed by measuring fluorochrome area, daily mineral apposition rate, and neoformed bone area using confocal laser microscopy. RT-PCR was performed to evaluate ALP and osteocalcin expression. The interface between newly formed bone and Biogran® was examined using scanning electron microscopy (SEM) and scanning transmission electron microscopy (STEM) at the micro-and nanoscale, respectively, while elemental analyses were completed in SEM with energy-dispersive X-ray spectroscopy (EDS). STEM imaging demonstrated the intimate attachment of bone to Biogran® (nanoscale level). Overall, the results suggest that the effectiveness of the topical administration of PTH 1-34 at the implant site seems enhanced in osteoporotic bone, promoting peri-implant bone regeneration to comparable levels in healthy conditions., 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.)

The dentin matrix is a collagenous scaffold structurally involved in anchoring resin-based materials to the tooth. Time-dependent degradation of this scaffold at the resin-dentin interface remains a core problem in adhesive dentistry, limiting the service life of dental fillings. This study explored the use of emergent materials termed metal-organic frameworks (MOFs)─formed by the self-assembly of metal ions and organic building blocks─to safeguard the collagen integrity in the functional dentin matrix. We demonstrate that collagen fibrils (from demineralized human dentin) can induce the biomimetic growth of MOF crystals as protective coatings to strengthen and stabilize the fibrils. Zeolitic imidazolate framework-8 (ZIF-8), a zinc-based microporous MOF, was used to fabricate the MOF composites via a "one-pot" reaction in water. The ZIF-modified dentin matrix presented superior mechanical strength and resistance to proteolysis, which can positively affect the longevity of collagen as an anchoring substrate. This work identifies a potential biomedical application of biomimetically synthesized MOFs in repairing dental tissues critical to restorative therapies.

Background: Multiple sclerosis (MS) is a neurologic disease of the central nervous system which affects almost three million people worldwide. MS is characterized by a demyelination process that leads to brain lesions, allowing these affected areas to be visualized with magnetic resonance imaging (MRI). Deep learning techniques, especially computational algorithms based on convolutional neural networks (CNNs), have become a frequently used algorithm that performs feature self-learning and enables segmentation of structures in the image useful for quantitative analysis of MRIs, including quantitative analysis of MS. To obtain quantitative information about lesion volume, it is important to perform proper image preprocessing and accurate segmentation. Therefore, we propose a method for volumetric quantification of lesions on MRIs of MS patients using automatic segmentation of the brain and lesions by two CNNs., Methods: We used CNNs at two different moments: the first to perform brain extraction, and the second for lesion segmentation. This study includes four independent MRI datasets: one for training the brain segmentation models, two for training the lesion segmentation model, and one for testing., Results: The proposed brain detection architecture using binary cross-entropy as the loss function achieved a 0.9786 Dice coefficient, 0.9969 accuracy, 0.9851 precision, 0.9851 sensitivity, and 0.9985 specificity. In the second proposed framework for brain lesion segmentation, we obtained a 0.8893 Dice coefficient, 0.9996 accuracy, 0.9376 precision, 0.8609 sensitivity, and 0.9999 specificity. After quantifying the lesion volume of all patients from the test group using our proposed method, we obtained a mean value of 17,582 mm 3 ., Conclusions: We concluded that the proposed algorithm achieved accurate lesion detection and segmentation with reproducibility corresponding to state-of-the-art software tools and manual segmentation. We believe that this quantification method can add value to treatment monitoring and routine clinical evaluation of MS patients.

(1) Background: There are many therapies for osteoporosis control and bone maintenance; anabolic drugs such as teriparatide and bone grafts help in the repair process and stimulate bone formation. Thus, the aim of the present study was to evaluate the behavior of repaired bone in the presence of PTH (teriparatide) associated with Biogran ® (biomaterial) through a sonochemical procedure after extraction in rats. (2) Methods: The insertion of Biogran ® with PTH in the alveolus was performed 30 days after incisor extraction. Euthanasia occurred after 60 days. (3) Results: The use of local treatment of PTH loaded with Biogran® in healthy rats promoted good results for micro-CT, with an increase in percentage and bone volume, number and trabecular separation and less total porosity. Greater immunostaining for Wnt, β-Catenin and osteocalcin proteins and lower expression for Thrombospondin-Related Adhesive Protein (TRAP), which shows an increase in the number of osteoblasts and inhibition of osteoclast action. However, the treated orchiectomized groups did not obtain such expressive results. (4) Conclusion: The use of Biogran ® with PTH improved alveolar repair in rats. However, new researches with more efficient doses must be studied to collaborate effectively with the formation of a quality bone after the orchiectomy.

Background: Glioblastoma is a fatal brain tumour with a poor patient survival outcome. Hypoxia has been shown to reprogram cells towards a stem cell phenotype associated with self-renewal and drug resistance properties. Activation of hypoxia-inducible factors (HIFs) helps in cellular adaptation mechanisms under hypoxia. Similarly, miRNAs are known to be dysregulated in GBM have been shown to act as critical mediators of the hypoxic response and to regulate key processes involved in tumorigenesis., Methods: Glioblastoma (GBM) cells were exposed to oxygen deprivation to mimic a tumour microenvironment and different cell aspects were analysed such as morphological changes and gene expression of miRNAs and survival genes known to be associated with tumorigenesis., Results: It was observed that miR-128a-3p, miR-34-5p, miR-181a/b/c, were down-regulated in 6 GBM cell lines while miR-17-5p and miR-221-3p were upregulated when compared to a non-GBM control. When the same GBM cell lines were cultured under hypoxic microenvironment, a further 4-10-fold downregulation was observed for miR-34-5p, miR-128a-3p and 181a/b/c while a 3-6-fold upregulation was observed for miR-221-3p and 17-5p for most of the cells. Furthermore, there was an increased expression of SOX2 and Oct4, GLUT-1, VEGF, Bcl-2 and survivin, which are associated with a stem-like state, increased metabolism, altered angiogenesis and apoptotic escape, respectively., Conclusion: This study shows that by mimicking a tumour microenvironment, miRNAs are dysregulated, stemness factors are induced and alteration of the survival genes necessary for the cells to adapt to the micro-environmental factors occurs. Collectively, these results might contribute to GBM aggressiveness., (© 2021. The Author(s).)

Objective: To characterize the effects of aging on the nanomechanical properties and 3D surface topographical parameters of an experimental Zirconia Toughened Alumina (ZTA) composite compared to its respective individual counterpart materials., Methods: Disk-shaped specimens comprised of three material groups were processed: 1) ZTA 70/30 (70% alumina reinforced with 30% second-generation 3Y-TZP); 2) Zpex (Second-generation 3Y-TZP), and; 3) Al 2 O 3 (High purity Alumina) (n = 10/material, 12 × 1 mm). After synthesis, ceramic powders were pressed, the green-body samples were sintered and polished. Nanoindentation testing was performed to record elastic modulus (E) and hardness (H). Interferometry was utilized to assess 3D surface roughness parameters (S a , S q ), while X-ray diffraction (XRD) and scanning electron microscope (SEM) assessed the crystalline content and microstructure. All tests were performed before and after simulated aging (134°C, 2.2 bar, 20 h). Statistical analyses were performed using linear mixed-model and least square difference pos-hoc tests (α = 5%)., Results: XRD spectra indicated increase of monoclinic peaks for Zpex (~18%) relative to ZTA 70/30 (~2.5%) after aging. Additionally, aging did not affect the surface roughness parameters of ZTA 70/30 and Al 2 O 3 , although a significant increase in S a was recorded for Zpex following aging (~90 nm) (p < 0.001). Al 2 O 3 yielded the highest H and E values (H:21 GPa, E: 254 GPa), followed by ZTA 70/30 (H: 13 GPa, E: 214 GPa) and Zpex (H:11 GPa, E: 167 GPa), all significantly different (p < 0.03)., Conclusion: ZTA 70/30 and Al 2 O 3 presented high hydrothermal stability with respect to all evaluated variables, where artificial aging significantly increased the monoclinic content and surface roughness of Zpex., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: RAS genes are among the most frequently mutated genes in cancer, where their mutation frequency varies according to the distinct RAS isoforms and tumour types. Despite occurring more prevalent in malignant tumours, RAS mutations were also observed in few benign tumours. Pituitary adenomas are examples of benign tumours which vary in size and aggressiveness. The present study was performed to investigate, via liquid biopsy and tissue analysis, the presence of K-RAS mutations in a pituitary macroadenoma., Methods: Molecular analysis was performed to investigate K-RAS mutations using the droplet digital PCR (ddPCR) method by evaluating both plasma (liquid biopsy) and the solid tumour of a patient diagnosed with a giant clinically non-functioning pituitary tumour., Results: The patient underwent surgical resection due to visual loss, and the histopathological analysis showed a gonadotrophic pituitary macroadenoma. The molecular analysis revealed the presence of mutant K-RAS both in the plasma and in the tumour tissue which, to our knowledge, has not been previously reported in the literature., Conclusion: Our findings highlight the exceptional capacity of the digital PCR in detecting low frequency mutations (below 1%), since we detected, for the first time, K-RAS mutations in pituitary macroadenoma. The potential impact of K-RAS mutations in these tumours should be further investigated., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The success of biomaterials for bone regeneration relies on many factors, among which osseointegration plays a key role. Biogran (BG) is a bioactive glass commonly employed as a bone graft in dental procedures. Despite its use in clinical practice, the capability of BG to promote osseointegration has never been resolved at the nanoscale. In this paper, we present the workflow for characterizing the interface between newly formed bone and BG in a preclinical rat model. Areas of bone-BG contact were first identified by backscattered electron imaging in a scanning electron microscope. A focused ion beam in situ lift-out protocol was employed to prepare ultrathin samples for transmission electron microscopy analysis. The bone-BG gradual interface, i.e. the biointerphase, was visualized at the nanoscale with unprecedented resolution thanks to scanning transmission electron microscopy. Finally, we present a method to view the bone-BG interface in three dimensions using electron tomography.

This in vitro study evaluated the impact of TiO2 nanotubes (n-TiO2) incorporated into glass ionomer cement (GIC) on Streptococcus mutans (S. mutans) characteristics at cellular and molecular levels. n-TiO2, synthesized by the alkaline method (20 nm in size), was added to Ketac Molar EasyMix® at 0%, 3%, 5%, and 7% by weight. S. mutans strains were cultured on GIC disks with addition or not of n-TiO2 for 1, 3, and 7 days and the following parameters were assessed: inhibition halo (mm) (n=3/group); cell viability (live/dead) (n=5/group); cell morphology (SEM) (n=3/group); and gene expression by real-time PCR (vicR, covR, gtfB, gtfC, and gtfD) (n=6/group). The data were analyzed by the Kruskal-Wallis test, repeated-measures ANOVA or two-way ANOVA, and Tukey's and Dunn's post-hoc tests (α=0.05). The agar diffusion test showed a higher antibacterial property for 5% n-TiO2 compared with 3% and 7% (p<0.05) with no effect of time (1, 3, and 7 days). The cell number was significantly affected by all n-TiO2 groups, while viability was mostly affected by 3% and 5% n-TiO2, which also affected cell morphology and organization. Real-time PCR demonstrated that n-TiO2 reduced the expression of covR when compared with GIC with no n-TiO2 (p<0.05), with no effect of time, except for 3% n-TiO2 on vicR expression. Within-group and between-group analyses revealed n-TiO2 did not affect mRNA levels of gtfB, gtfC, and gtfD (p>0.05). Incorporation of n-TiO2 at 3% and 5% potentially affected S. mutans viability and the expression of key genes for bacterial survival and growth, improving the anticariogenic properties of GIC.

Implant placement is an important repair method in dentistry and orthopedics. Increasing efforts have focused on optimizing the biocompatibility and osseointegration properties of titanium (Ti) and Ti-based alloys. In this work, Ti-based alloys were modified by the layer-by-layer (LbL) technique, which is a simple and versatile method for surface modification. The morphology and chemical structure of LbL films of poly(sodium 4-styrenesulfonate) (PSS) and Ti dioxide (TiO 2 ) nanoparticles were first characterized employing ultraviolet-visible and Fourier-transform infrared spectroscopies as well as atomic force microscopy for further application in Ti-based alloy implants. The changes provoked by the LbL PSS/TiO 2 film on the Ti-based alloy surfaces were then investigated by scanning electron microscopy and micro-Raman techniques. Finally, in vivo tests (immunolabeling and biomechanical analysis) performed with screw implants in rats suggested that PSS/TiO 2 multilayers promote changes in both topography and chemical surface properties of the screw, providing beneficial effects for osteoblast activity. This simple and relatively low-cost growth process can open up possibilities to improve dental implants and, probably, bone implants in general.

Knowledge of viral load is essential to formulate strategies for antiviral treatment, vaccination, and epidemiological control of COVID-19. Moreover, identification of patients with high viral loads can also be useful to understand risk factors such as age, comorbidities, severity of symptoms and hypoxia, to decide on the need for hospitalization. Several ongoing studies are analyzing viral load in different types of samples and evaluating its relationship with clinical outcomes and viral transmission pathways. However, in a great number of emerging studies, cycle threshold (Ct) values alone are often used as viral load indicators, which may be a mistake. In this study, we compared tracheal aspirate with nasopharyngeal swab samples obtained from critically ill COVID-19 patients and here we report how the raw Ct can lead to misinterpretation of results. Furthermore, based on analysis of nasopharyngeal swab samples we propose a method to reduce evaluation errors that could occur from using raw Ct data. Based on these findings, we show the impact that normalization of Ct values has on interpretation of SARS-CoV-2 viral load from different biological samples., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The use of polymer additives that stabilize fluidic amorphous calcium phosphate is key to obtaining intrafibrillar mineralization of collagen in vitro. On the other hand, this biomimetic approach inhibits the nucleation of mineral crystals in unconfined extrafibrillar spaces, that is, extrafibrillar mineralization. The extrafibrillar mineral content is a significant feature to replicate from hard connective tissues such as bone and dentin as it contributes to the final microarchitecture and mechanical stiffness of the biomineral composite. Herein, we report a straightforward route to produce densely mineralized collagenous composites via a surface-directed process devoid of the aid of polymer additives. Simulated body fluid (1×) is employed as a biomimetic crystallizing medium, following a preloading procedure on the collagen surface to quickly generate the amorphous precursor species required to initiate matrix mineralization. This approach consistently leads to the formation of extrafibrillar bioactive minerals in bulk collagen scaffolds, which may offer an advantage in the production of osteoconductive collagen-apatite materials for tissue engineering and repair purposes.

Background: Convalescent plasma is a potential therapeutic option for critically ill patients with coronavirus disease 19 (COVID-19), yet its efficacy remains to be determined. The aim was to investigate the effects of convalescent plasma (CP) in critically ill patients with COVID-19. Methods: This was a single-center prospective observational study conducted in Rio de Janeiro, Brazil, from March 17th to May 30th, with final follow-up on June 30th. We included 113 laboratory-confirmed COVID-19 patients with respiratory failure. Primary outcomes were time to clinical improvement and survival within 28 days. Secondary outcomes included behavior of biomarkers and viral loads. Kaplan-Meier analyses and Cox proportional-hazards regression using propensity score with inverse-probability weighing were performed. Results: 41 patients received CP and 72 received standard of care (SOC). Median age was 61 years (IQR 48-68), disease duration was 10 days (IQR 6-13), and 86% were mechanically ventilated. At least 29 out of 41CP-recipients had baseline IgG titers ≥ 1:1,080. Clinical improvement within 28 days occurred in 19 (46%) CP-treated patients, as compared to 23 (32%) in the SOC group [adjusted hazard ratio (aHR) 0.91 (0.49-1.69)]. There was no significant change in 28-day mortality (CP 49% vs. SOC 56%; aHR 0.90 [0.52-1.57]). Biomarker assessment revealed reduced inflammatory activity and increased lymphocyte count after CP. Conclusions: In this study, CP was not associated with clinical improvement or increase in 28-day survival. However, our study may have been underpowered and included patients with high IgG titers and life-threatening disease. Clinical Trial Registration: The study protocol was retrospectively registered at the Brazilian Registry of Clinical Trials (ReBEC) with the identification RBR-4vm3yy (http://www.ensaiosclinicos.gov.br)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kurtz, Righy, Gadelha, Bozza, Bozza, Gonçalves, Bastos, Vale, Higa, Castilho, Monteiro, Charris, Fialho, Turon, Guterres, Lyra Miranda, de Azeredo Lima, de Caro, Prazeres, Ventura, Gaspari, Miranda, Jose da Mata, Pêcego, Mateos, Lopes, Castilho, Oliveira, Boquimpani, Rabello, Lopes, Neto, Ferreira, Tanuri, Filho and Amorim.)