Influence of straight versus angulated screw channel titanium bases on failure loads of two-piece ceramic and titanium implants restored with screw-retained monolithic crowns: An in-vitro study.

OBJECTIVE: To analyze the influence of titanium-base (straight [SSC]/angulated-screw-channel [ASC]) on failure-loads and bending-moments of two-piece ceramic and titanium-zirconium implants restored with monolithic-zirconia crowns after fatigue. MATERIALS AND METHODS: Thirty-two anterior monolithic-screw-retained zirconia crowns were divided into four groups (n = 8/group) according to the factors: (1) type of implant material: two-piece titanium-zirconium implant (Ti-Zr; control-group) versus two-piece ceramic implant (CI; test-group) and (2) type of titanium-base: SSC (0° angle) versus ASC (25°). An intact implant was used for field emission gun-scanning electronic microscopy (FEG-SEM) characterization and Raman spectroscopy for phase analyses and residual stress quantification. All samples were exposed to fatigue with thermodynamic loading (1.2-million-cycles, 49 N, 1.6 Hz, 5-55°C) at a 30° angle. Surviving specimens were loaded until failure (SLF) and bending moments were recorded. Failed samples were examined using light microscope and SEM. Statistical analyses included ANOVA and Mann-Whitney U-test. RESULTS: Raman-spectroscopy revealed the presence of residual compressive stresses. FEG-SEM revealed a roughened surface between threads and polished surface at the cervical-collar of the ceramic implant. All samples survived fatigue and were free of complications. Mean bending-moments (±SD) were: Ti-Zr-0: 241 ± 45 N cm, Ti-Zr-25: 303 ± 86 N cm, CI-0: 326 ± 58 N cm, CI-25: 434 ± 71 N cm. Titanium-base and implant-material had significant effects in favor of ASC titanium bases (p = .001) and ceramic-implants (p < .001). Failure analysis after SLF revealed severe fractures in ceramic implants, whereas titanium implants were restricted to plastic deformation. CONCLUSIONS: Ceramic and titanium implants exhibited high reliability after fatigue, with no failures. From a mechanical perspective, titanium bases with ASC can be recommended for both ceramic and titanium implants and are safe for clinical application.

Water as Veneering Modeling Liquid Affects Microhardness of Glassy Matrix Veneering Ceramic.

PURPOSE/AIM: To evaluate the effect of different veneering liquids used for modeling on microhardness, fracture toughness and biaxial flexural strength of a glass-veneering ceramic. MATERIAL AND METHODS: The manufacturer recommended modeling liquid (ML), distilled water (DW), isopropyl alcohol (IA), 0.5% (P05), 1% (P1), and 2% (P2) polyethylene glycol solutions were mixed with feldspathic ceramic powder to form disc-shaped samples (n=20, 15 mm × 1.2 mm). After sintering, samples were mirror-polished and subjected to Vickers indentation (n=5) for measurement of microhardness and fracture toughness. The remaining 15 samples from each group were subjected to biaxial flexural strength. Data were subjected to one-way ANOVA and Weibull analysis. RESULTS: The microhardness was affected by veneering liquid (p=0.002): DW promoted higher microhardness values than ML and IA. Fracture toughness (p=0.301) and flexural strength (p=0.930) were not affected by the veneering liquid but Weibull parameters were affected. All groups presented surface pores under high magnification. CONCLUSION: Even though the use of DW led to higher values of surface microhardness than the ML, all obtained values are inside the range of enamel microhardness values reported in the literature. Such parameters may affect antagonist wear and should be reported in clinical trials.

Anthropogenic control over wintertime oxidation of atmospheric pollutants.

During winter in the mid-latitudes, photochemical oxidation is significantly slower than in summer and the main radical oxidants driving formation of secondary pollutants, such as fine particulate matter and ozone, remain uncertain, owing to a lack of observations in this season. Using airborne observations, we quantify the contribution of various oxidants on a regional basis during winter, enabling improved chemical descriptions of wintertime air pollution transformations. We show that 25-60% of NOx is converted to N2O5 via multiphase reactions between gas-phase nitrogen oxide reservoirs and aerosol particles, with ~93% reacting in the marine boundary layer to form >2.5 ppbv ClNO2. This results in >70% of the oxidizing capacity of polluted air during winter being controlled, not by typical photochemical reactions, but from these multiphase reactions and emissions of volatile organic compounds, such as HCHO, highlighting the control local anthropogenic emissions have on the oxidizing capacity of the polluted wintertime atmosphere.

The characterization of Bordetella pertussis strains isolated in the Central-Western region of Brazil suggests the selection of a specific genetic profile during 2012-2014 outbreaks.

Pertussis is a worldwide acute respiratory disease caused by the bacterium Bordetella pertussis. Despite high vaccine coverage, the bacterium continues to circulate in populations and is still one of the most common vaccine-preventable diseases. In Brazil, pertussis incidence has presented a significant decrease since 1990 but since 2011 a sudden increase in incidence has been observed. Thus, the aim of this study was to perform a molecular epidemiological characterization of B. pertussis strains isolated in the Central-Western region (specifically in Distrito Federal) of Brazil from August 2012 to August 2014. During this period, 92 B. pertussis strains were isolated from the outbreaks. All strains were characterized by serotyping and XbaI pulsed-field gel electrophoresis profiles. From August to December 2012, the most prevalent serotype observed was 1,3 (13/17). During 2013 the prevalence of serotype 1,3 decreased (13/30) and from January 2014 to August 2014 the most prevalent serotype was 1,2 (33/45). Fourteen PFGE profiles were identified. Of these, BP-XbaI0039 prevalence increased from 3/17 in 2012 to 10/30 in 2013, and 35/45 in 2014. These results evidence the selection of a specific genetic profile during this period, suggesting the occurrence of a bacterial genomic profile with high circulation potential.

Contemporary pollen and seed dispersal in natural populations of Bertholletia excelsa (Bonpl.).

Due to the nutritional content and commercial value of its seeds, Bertholletia excelsa is one of the most important species exploited in the Amazon region. The species is hermaphroditic, insect pollinated, and its seeds are dispersed by barochory and animals. Because the fruit set is dependent on natural pollinator activity, gene flow plays a key role in fruit production. However, to date, there have been no studies on pollen and seed flow in natural populations of B. excelsa. Herein, we used microsatellite loci and parentage analysis to investigate the spatial genetic structure (SGS), realized pollen and seed dispersal, and effective pollen dispersal for two B. excelsa populations in the Brazilian Amazon forest. Two plots were established in natural forests from which adults, juveniles, and seeds were sampled. Realized and effective pollen flow was greater than realized seed flow. The distance of realized pollen dispersal ranged from 36 to 2060 m, and the distance of realized seed dispersal ranged from 30 to 1742 m. Both pollen and seeds showed a dispersal pattern of isolation by distance, indicating a high frequency of mating among near-neighbor trees and seed dispersal near to mother trees. Both populations present SGS up to 175 m, which can be explained by isolation by distance pollen and seed dispersal patterns. Our results suggested that fragmentation of these forest populations may result in a significant decrease in gene flow, due to the isolation by distance pollen and seed dispersal patterns.

Increasing springtime ozone mixing ratios in the free troposphere over western North America.

In the lowermost layer of the atmosphere-the troposphere-ozone is an important source of the hydroxyl radical, an oxidant that breaks down most pollutants and some greenhouse gases. High concentrations of tropospheric ozone are toxic, however, and have a detrimental effect on human health and ecosystem productivity. Moreover, tropospheric ozone itself acts as an effective greenhouse gas. Much of the present tropospheric ozone burden is a consequence of anthropogenic emissions of ozone precursors resulting in widespread increases in ozone concentrations since the late 1800s. At present, east Asia has the fastest-growing ozone precursor emissions. Much of the springtime east Asian pollution is exported eastwards towards western North America. Despite evidence that the exported Asian pollution produces ozone, no previous study has found a significant increase in free tropospheric ozone concentrations above the western USA since measurements began in the late 1970s. Here we compile springtime ozone measurements from many different platforms across western North America. We show a strong increase in springtime ozone mixing ratios during 1995-2008 and we have some additional evidence that a similar rate of increase in ozone mixing ratio has occurred since 1984. We find that the rate of increase in ozone mixing ratio is greatest when measurements are more heavily influenced by direct transport from Asia. Our result agrees with previous modelling studies, which indicate that global ozone concentrations should be increasing during the early part of the twenty-first century as a result of increasing precursor emissions, especially at northern mid-latitudes, with western North America being particularly sensitive to rising Asian emissions. We suggest that the observed increase in springtime background ozone mixing ratio may hinder the USA's compliance with its ozone air quality standard.

The dental pulp stem cell niche based on aldehyde dehydrogenase 1 expression.

AIM: To detect cells expressing the stem cell marker ALDH1 (aldehyde dehydrogenase1) in the pulp of human permanent teeth and to investigate the expression of ALDH1 in isolated dental pulp cells. METHODOLOGY: Pulp tissue was collected and processed for immunohistochemistry to detect ALDH1-, STRO-1- and CD90-positive cells. In addition, cells were isolated and analysed by flow cytometry for ALDH1 activity and for the cell surface markers CD44, CD73, CD90, STRO-1 and CD45. Cells were also examined for multidifferentiation capacity. Within these cells, an ALDH1(+) cell subpopulation was selected and evaluated for multidifferentiation capacity. RESULTS: The immunohistochemistry analyses showed that ALDH1-, CD90- and STRO-1-positive cells were located mainly in the perivascular areas and nerve fibres of dental pulps. Cells on the fifth passage had high expression for CD44, CD73 and CD90, whereas moderate labelling was observed for STRO-1 and ALDH1 in flow cytometry analysis. On the same passages, cells were able to differentiate into osteogenic, adipogenic and chondrogenic lineages. The ALDH1(+) cell subpopulation also demonstrated multilineage differentiation ability. CONCLUSIONS: Dental pulp stem cells reside in the vicinity of blood vessels and nerve fibres, indicating the possible existence of more than one stem cell niche in dental pulps. Furthermore, ALDH1 was expressed by isolated dental pulp cells, which had mesenchymal stem cell characteristics. Thus, it can be suggested that ALDH1 may be used as a DPSC marker.

Genetic diversity of the forage peanut in the Jequitinhonha, São Francisco, and Paranã River valleys of Brazil.

Arachis pintoi and A. repens are legumes with a high forage value that are used to feed ruminants in consortium systems. Not only do they increase the persistence and quality of pastures, they are also used for ornamental and green cover. The objective of this study was to analyze microsatellite markers in order to access the genetic diversity of 65 forage peanut germplasm accessions in the section Caulorrhizae of the genus Arachis in the Jequitinhonha, São Francisco and Paranã River valleys of Brazil. Fifty-seven accessions of A. pintoi and eight of A. repens were analyzed using 17 microsatellites, and the observed heterozygosity (HO), expected heterozygosity (HE), number of alleles per locus, discriminatory power, and polymorphism information content were all estimated. Ten loci (58.8%) were polymorphic, and 125 alleles were found in total. The HE ranged from 0.30 to 0.94, and HO values ranged from 0.03 to 0.88. By using Bayesian analysis, the accessions were genetically differentiated into three gene pools. Neither the unweighted pair group method with arithmetic mean nor a neighbor-joining analysis clustered samples into species, origin, or collection area. These results reveal a very weak genetic structure that does not form defined clusters, and that there is a high degree of similarity between the two species.

Transforming growth factor-β and matrix metalloproteinase secretion in cell culture from ex-vivo pbmc after exposure to uv radiation.

Transforming Growth Factor-beta (TGF-beta) and Matrix metalloproteinases (MMPs) especially MMP-2 and MMP-9, secreted by a pool of cells from dermic-epidermic tissue, might be associated with a poor prognosis of cancer. We examined the effect of solar radiation on the secretion of TGF-beta, MMP-2 and MMP-9 by ex vivo PBMC and dermic-epidermic cell pool. The two pools of cells in culture were photo tested using a solar simulator which reproduces the natural light source. The cells were incubated in serum-free medium in the absence and presence of PHA. After two 5 and 45 min exposure times, the supernatant of the cultures was removed at 24 and 48 h and analyzed for TGF-beta, and disrupted cell samples for MMP-2 and MMP-9 by RT-PCR. The data obtained by Optical Density by ELISA showed significant differences in the production of TGF-beta to the exposed cultures compared to control at 24 and 48 h, respectively. The increases in the MMP-2 and MMP-9 concentrations depending on the exposure time were observed. In conclusion, the UV radiation emitted by the solar simulator was able to stimulate the cells from extracellular matrix in in vitro culture to TGF-beta production, MMP-2 and MMP-9 expressions and their mRNAs. Since such MMPs and TGF are related to the evolution of cancer and its pathogenesis, these findings confirm that UV radiation can contribute to the prognosis of such diseases based on the MMP and TGF-beta secretion.

Masticatory efficiency in complete denture wearers with reduced dental arches--a randomised cross-over study.

One obstacle to placing artificial posterior teeth in manufacturing complete dentures is a reduction of the space between the maxilla and the mandible. Occasionally, second molar placement is not performed, as it does not affect aesthetics, phonetics or comfort. The aim of this study was to compare the masticatory efficiency between patients wearing maxillary and mandibular complete dentures with reduced dental arches (without second molars) (WSM) and with full dental arches (FDA). Twenty subjects were divided into two groups and randomly received new complete dentures. Patients in Group 1 were given dentures WSM, and those in Group 2 were given dentures with FDA. After the post-placement visits, an initial masticatory efficiency test was performed with Optocal, an artificial test food. Fifteen days later, second molars were placed in Group 1 and removed from Group 2, and a new test was performed. Comminuted material was treated and sieved under vibration. The mean and standard deviation of masticatory efficiency with FDA were 10.4 and 8.1, respectively. In the tests WSM, the mean and standard deviation were 8.4 and 3.3, respectively. After removing the second molars in Group 2 and adding them in Group 1, the mean and standard deviation were 15.7 and 14.7 for Group 1 and 12.5 and 10.4 for Group 2, respectively. Within the limitations of this study, placing artificial teeth up to the first molars can be performed when needed without compromising masticatory efficiency.

The genetic landscape of mitochondrial diseases in the next-generation sequencing era: a Portuguese cohort study.

Introduction: Rare disorders that are genetically and clinically heterogeneous, such as mitochondrial diseases (MDs), have a challenging diagnosis. Nuclear genes codify most proteins involved in mitochondrial biogenesis, despite all mitochondria having their own DNA. The development of next-generation sequencing (NGS) technologies has revolutionized the understanding of many genes involved in the pathogenesis of MDs. In this new genetic era, using the NGS approach, we aimed to identify the genetic etiology for a suspected MD in a cohort of 450 Portuguese patients. Methods: We examined 450 patients using a combined NGS strategy, starting with the analysis of a targeted mitochondrial panel of 213 nuclear genes, and then proceeding to analyze the whole mitochondrial DNA. Results and Discussion: In this study, we identified disease-related variants in 134 (30%) analyzed patients, 88 with nuclear DNA (nDNA) and 46 with mitochondrial DNA (mtDNA) variants, most of them being pediatric patients (66%), of which 77% were identified in nDNA and 23% in mtDNA. The molecular analysis of this cohort revealed 72 already described pathogenic and 20 novel, probably pathogenic, variants, as well as 62 variants of unknown significance. For this cohort of patients with suspected MDs, the use of a customized gene panel provided a molecular diagnosis in a timely and cost-effective manner. Patients who cannot be diagnosed after this initial approach will be further selected for whole-exome sequencing. Conclusion: As a national laboratory for the study and research of MDs, we demonstrated the power of NGS to achieve a molecular etiology, expanding the mutational spectrum and proposing accurate genetic counseling in this group of heterogeneous diseases without therapeutic options.

Effect of calcination on minimally processed recycled zirconia powder derived from milling waste.

OBJECTIVE: To assess the influence of calcination process on the properties of minimally processed recycled 3Y-TZP, and to compare it with its commercial counterpart. METHODS: Non-milled 3Y-TZP waste was collected, fragmented and ball-milled to a granulometric < 5 µm. Half of the recycled powder was calcined at 900 °C. Recycled 3Y-TZP disks were uniaxially pressed and sintered to create two recycled groups: 1) Calcined and 2) Non-calcined to be compared with a commercial CAD/CAM milled 3Y-TZP. The microstructure of experimental groups was assessed through density (n = 6), scanning electron microscopy (n = 3) and energy-dispersive X-ray spectroscopy (n = 3); and the crystalline content was evaluated through X-ray diffraction (XRD) (n = 3). Optical and mechanical properties were investigated through reflectance tests (n = 10), and Vickers hardness, fracture toughness (n = 5), and biaxial flexural strength tests (n = 16), respectively. Fractographic analysis was performed to identify fracture origin and crack propagation. Statistical analyses were performed through ANOVA followed by Tukey´s test, and by Weibull statistics. RESULTS: Particle size distribution of recycled powder revealed an average diameter of ∼1.60 µm. The relative density of all experimental groups was > 98.15 % and XRD analysis exhibited a predominance of tetragonal-phase in both recycled groups, which were similar to the crystallographic pattern of the control group. Cross-section micrographs presented flaws on the non-calcined group, and a more homogeneous microstructure for the calcined and commercial groups. Commercial samples showed lower contrast-ratio and higher translucency-parameter than the recycled groups, where non-calcined presented higher translucency-parameter and lower contrast-ratio than its calcined counterpart. The commercial group presented higher fracture toughness and characteristic strength than the recycled groups. Moreover, the calcined group exhibited higher hardness, characteristic strength, and probability of survival at higher loads than the non-calcined group. Fractographic analysis depicted the presence of microstructural flaws in the non-calcined group, which may have acted as stress-raisers and led to failures at lower flexural strengths values. SIGNIFICANCE: The calcination process improved the microstructure, optical, and mechanical properties of the recycled 3Y-TZP.

Phenotypic behavior of PBMCs from irradiated dogs based on flow cytometry.

The present paper investigates the phenotypic parameters of stimulation markers and cell immunosuppression markers in an animal model using flow cytometry analysis. Six dogs were exposed to 2, 4 or 6 Gy following a head and neck protocol. Samples of peripheral blood mononuclear cells (PBMCs) were collected before irradiation, representing standard values for all dogs (control), and at 2 h, 18 h and 30 d after irradiation. Such samples were separately assessed for surface markers with the monoclonal antibodies anti-CD5, anti-CD4 and anti-CTLA-4 by flow cytometry. A reduction in Tcell expression of CD5 and in the subpopulation expressing CD4 and an increase in CTLA-4 expression were found. No statistically significant differences were observed for the absorbed dose grouping, although the time kinetics were recorded. Radiation induced phenotypic differences between the lymphocyte lineages, reducing the CD5 and CD4 Tcell subpopulations and increasing CTLA-4 expression. The findings demonstrate the relevance of investigating the immunophenotype of irradiated subjects by examining the peripheral cell lineage.

Synthesis and characterization of calcium phosphate loaded with Ho-166 and Sm-153: a novel biomaterial for treatment of spine metastases.

Spine metastases are a common and painful complication of cancer. A novel concept of treatment combines the in situ vertebroplasty with radiotherapy employing radioactive bone cement into the human vertebrae. Thus, investigations concerning possible bioactive and radioactive cements become a relevant theme. In this work, we have synthesized calcium phosphate bioceramics incorporated with Ho and Sm nuclides using sol-gel technique. Characterizations were performed using X-ray diffractometry, infrared spectroscopy, scanning electron microscopy, instrumental neutron activation analysis, and gamma spectroscopy. Results showed bioceramics composed by multiphasic calcium phosphates along with holmium and samarium phosphates, with 8.9 and 13.7 % of Sm and Ho in weight, respectively. After neutron activation, the Ho-166 and Sm-153 beta-emitters were identified and quantified on the bioceramics with activities estimated at 32.5 and 14.5 MBq/mg of Sm-153 and Ho-166 bioceramic powder, respectively. These radioactive calcium phosphate bioceramics can compose suitable radioactive cements to radiovertebroplasty.

New efficient DNA extraction method to access the microbiome of Ricinus communis seeds.

Ricinus communis (castor bean) seeds are used to produce an alcohol-soluble oil that is used in more than 400 industrial processes. Despite its economic importance, there has been little research on the endophytic microbiota of castor bean seeds. This microbiota is important for plant metabolic processes and may have considerable biotechnological potential, such as production of lipases and plant growth promoter agents. We evaluated several DNA extraction methodologies in order to access the microbial diversity of castor bean through a metagenomic approach. Based on our observations, we developed a new methodology that takes advantage of the low solubility of calcium phosphates and the high affinity of these phosphates for proteins and polysaccharides. The extracted DNA quality was evaluated by PCR, using a selective primer pair for bacterial and mitochondrial 16S rDNA genes (799F and 1492R). We found this methodology quantitatively and qualitatively more efficient than the other approaches. In evaluating this new extraction methodology, we found that the difficulties of DNA extraction from castor bean seeds, such as abundant oil, polysaccharides, phenolic compounds, and plant enzymes, could be overcome. The resulting extracts had high concentration and purity, and they were obtained faster than with previous methods. The samples contained virtually all of the DNA, including the microbial DNA; this was validated by PCR analysis.

Incidence of bovine leukocyte adhesion deficiency, complex vertebral malformation, and deficiency of uridine-5-monophosphate synthase carriers in Brazilian Girolando cattle.

Among the various hereditary diseases that have been widely studied in dairy cattle, bovine leukocyte adhesion deficiency (BLAD), deficiency of uridine-5-monophosphate synthase (DUMPS), and complex vertebral malformation (CVM) are noteworthy because of their high impact on overall herd productivity as a consequence of increased calf mortality. The aim of this study was to verify the frequency of carriers of BLAD, CVM, and DUMPS mutant alleles in cows and bulls from the National Girolando Progeny Test carried out in Brazil by using polymerase chain reaction (PCR)-restriction fragment length polymorphism and allele-specific PCR assays. A total of 777 animals were genotyped for BLAD, 783 for CVM, and 122 for DUMPS. The frequencies of carriers for BLAD and CVM were 0.77 and 1.53%, respectively, whereas no carriers of DUMPS were observed.

Infiltration OF 5Y-PSZ with thermally compatible glass: Strength, microstructure and failure mode analyses.

This study set out to develop a thermally compatible glass to be infiltrated into zirconia partially stabilized by yttrium oxide (5Y-PSZ), to characterize it, and to evaluate its structural reliability and mechanical behavior. 5Y-PSZ zirconia discs (N = 90), dimensions 1.5 mm × 15 mm were produced, polished with #600 alumina oxide and #1200 silicon carbide sandpaper in a polisher. Three groups of 5Y-PSZ discs were assigned (n = 30): Zctrl: as sintered zirconia, Zinf-comp: glass-infiltrated zirconia on the occlusal surface, and sintered, and Zinf-tens: glass-infiltrated zirconia on the cementing surface and sintered; for biaxial flexural strength testing (ISO 6872:2015). A gel was synthesized via the sol-gel method and applied to the ceramic surface. Mechanical assay data (MPa) were evaluated via Weibull analysis (α = 5%) and specimens via X-Ray Diffractometry (XRD), Scanning Electron Microscopy (SEM), and fractographic analysis. The Zinf-tens group showed a characteristic strength of 824 MPa and m = 9.9; Zinf-comp 613 MPa and m = 10.2; Zctrl 534 MPa and m = 8; all groups differed statistically (σ0). However, they were similar in structural homogeneity (m). XRD showed 20-50 µm of infiltration, which means dissolution of part of the yttrium and reduction in the size of the cubic grains. In addition, the Zinf-tens group presented a failure origin from inside the material. The developed glass infiltrated into zirconia partially stabilized by yttrium oxide, increasing its characteristic strength and structural homogeneity by reducing surface defects and changing the failure mode.

Recurrence of low back pain: A difficult outcome to predict. Development and validation of a multivariable prediction model for recurrence in patients recently recovered from an episode of non-specific low back pain.

BACKGROUND: Recurrence of low back pain (LBP) is common. If clinicians could identify an individual's risk of recurrence, this would enhance clinical decision-making and tailored patient care. OBJECTIVE/DESIGN: To develop and validate a simple tool to predict the probability of a recurrence of LBP by 3- or 12-months following recovery. METHODS: Data utilised for the prediction model development came from a prospective inception cohort study of participants (n = 250) recently recovered from LBP, who had sought care from chiropractic or physiotherapy services. The outcome measure was a recurrence of activity-limiting LBP. Candidate predictor variables (e.g., basic demographics, LBP history, levels of physical activity, etc) collected at baseline were considered for inclusion in a multivariable Cox model. The model's performance was tested in a separate validation dataset of participants (n = 261) involved in a randomised controlled trial investigating exercise for the prevention of LBP recurrences. RESULTS: The final model included the number of previous episodes, total sitting time, and level of education. In the development sample, discrimination was acceptable (Harrell's C-statistic = 0.61, 95% CI, 0.59-0.62), but in the validation sample, discrimination was poor (0.56, 95% CI, 0.54-0.58). Calibration of the model in the validation dataset was acceptable at 3 months but was less precise at 12 months. CONCLUSION: The developed prediction model, which included number of previous episodes, total sitting time, and level of education, did not perform adequately in the validation sample to recommend its use in clinical practice. Predicting recurrence of LBP in clinical practice remains challenging.

A phase II clinical trial of sunitinib following hepatic transarterial embolization for metastatic neuroendocrine tumors.

BACKGROUND: The liver is the predominant site of metastases among patients with advanced neuroendocrine tumors (NETs). Prior retrospective studies have reported high response rates in patients treated with transarterial embolization (TAE). NETs are highly vascular and are known to express vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR). We hypothesized that administration of sunitinib, a VEGFR inhibitor, following TAE would extend progression-free survival (PFS). PATIENTS AND METHODS: Patients with metastatic NETs to the liver underwent a series of selective TAEs followed by sunitinib (until disease progression or maximum of 12 months). Radiographic response (by RECIST), survival, and safety parameters were monitored. RESULTS: Thirty-nine patients were enrolled. The overall response rate was 72% [95% confidence interval (CI), 0.58-0.86]. Median PFS was 15.2 months. Rates of overall survival (OS) at 1 and 4 years were 95% (95% CI, 0.88-1.00) and 59% (95% CI, 0.38-0.80), respectively. A significant 34% rise in serum VEGF was observed following the initial TAE (P = 0.03). CONCLUSIONS: Hepatic TAE is a highly active treatment option for patients with metastatic NETs to the liver. Embolization stimulates release of VEGF into the circulation. Sunitinib, an oral VEGFR inhibitor, can be safely administered following embolization. The high rates of PFS and OS associated with this sequence of therapies are encouraging.

Incorporation of 45S5 bioglass via sol-gel in ß-TCP scaffolds: Bioactivity and antimicrobial activity evaluation.

In this work, ß-TCP (ß-tricalcium phosphate) bioresorbable scaffolds were prepared by the gel casting method. Then, they were impregnated with a 45S5 bioglass sol gel solution to improve biocompatibility and promote bioactivity and antimicrobial activity. The ß-TCP scaffolds had an apparent porosity of 72%, and after the incorporation of the bioglass, this porosity was maintained. The elements of the bioglass were incorporated into ß-TCP matrix and there was a partial transformation from the ß-TCP phase to the α-TCP (α-tricalcium phosphate) phase, besides the formation of bioactive calcium and sodium­calcium silicates. The scaffolds ß-TCP with 45S5 bioglass incorporated (ß-TCP/45S5) did not show a reduction in their values of mechanical strength and Weibull modulus, despite the partial transformation to the α-TCP phase. Bioactivity, cell viability, and antimicrobial activity improved significantly for the ß-TCP/45S5 scaffold comparing to the scaffold without the bioglass. The mineralization of carbonated hydroxyapatite was verified in Simulated Body Fluid (SBF). The cell viability, evaluated by the reduction of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide - MTT in MG63 cells, increased by 178%, and ß-TCP/45S5 scaffold also enhanced cell activity and osteoblast differentiation observed by means of total protein contend and alkaline phosphatase activity, respectively. The formation of growth inhibition zones was also observed in the disk diffusion assay for three tested microorganisms: Staphylococcus aureus, Escherichia coli and Candida albicans. To conclude, the vacuum impregnation method in 45S5 bioglass sol gel solution was effective in penetrating all the interconnected macroporosity of the scaffolds and covering the surface of the struts, which improved their biological properties in vitro, bioactivity and antibacterial activity, without reducing mechanical strength and porosity values. Thus, the ß-TCP/45S5 scaffolds are shown as potential candidates for use in tissue engineering, mainly in bone tissue regeneration and recovery.