The mineralizing effect of zinc oxide-modified hydroxyapatite-based sealer on radicular dentin

Objective To evaluate the remineralization ability of three endodontic sealer materials at different root dentin regions. Material and methods Cervical, medial and apical root dentin surfaces were treated with two experimental hydroxyapatite-based cements, containing sodium hydroxide (calcypatite) or zinc oxide (oxipatite); an epoxy resin-based canal sealer, AH Plus; and gutta-percha. Remineralization, at the inner and outer zones of dentin disk surfaces, was studied by nanohardness (Hi) and Raman analysis. Nano-roughness and collagen fibrils width measurements were performed. Numerical data, at 24 h or 12 m, were analyzed by ANOVA and Student-Newman-Keuls (P<0.05). Results At the outer and inner zones of cervical dentin treated with oxipatite, the highest Hi after 12 m of immersion was achieved. The same group showed the highest intensity of phosphate peak, markers for calcification and crystallinity. Nanoroughness was lower and fibrils diameter was higher at the inner zone of dentin treated with oxipatite. Dentin mineralization occurred in every region of root dentin treated with oxipatite and calcypatite, especially at inner zone of dentin after 12 m. Conclusions Oxipatite, reinforced the inner root zone at any third of radicular dentin, by increasing both nanohardness and remineralization. When using calcypatite, the highest nanohardness was found at the apical third of the inner root dentin, but the lowest mechanical performance was obtained at the cervical and the medial thirds of the roots. Therefore, application of oxipatite as sealing cement of root canals is recommended. Clinical relevance Oxipatite, when used as endodontic sealing material, strengthens radicular dentin.Project MAT2017-85999-P MINECO/AEI/FEDER/UE supported by the Ministry of Economy and Competitiveness (MINECO) and European Regional Development Fund (FEDER)

A zinc oxide-modified hydroxyapatite-based cement favored sealing ability in endodontically treated teeth

Objectives: To evaluate the effectiveness of different endodontic canal sealers for dentin permeability reduction and to determine the viscoelastic performance of root dentin after their application. Methods: Cervical, medial and apical root dentin surfaces were treated with two experimental hydroxyapatite-based cements, containing sodium hydroxide (calcypatite) or zinc oxide (oxipatite); an epoxy resin- based canal sealer, AH Plus; and gutta-percha. Root dentin was evaluated for fluid filtration. Field emission scanning electron microscopy, energy dispersive analysis, AFM, Young’s modulus and Nano-DMA analysis were also performed, at the inner and outer zones of dentin. Results: Dentin treated with oxipatite showed the lowest microleakage among groups with hermetically sealed tubules and zinc-based salt formations. Samples treated with oxipatite showed the highest Ei at the cervical dentin third among groups, at 6 m of storage. Oxipatite promoted the highest complex modulus and tan delta values at the inner zone of both cervical and medial root dentin. Calcypatite favored the lowest tan delta outcomes at the inner zone of apical dentin at 6 m. Conclusions: Specimens treated with oxipatite showed the highest sealing ability, based on the highest Young’s modulus and dentin mineralization, achieved by closing dentinal tubules, voids and pores that reinforced the inner zone of root dentin. The homogeneity of viscoelastic properties among the different root dentin thirds favored the energy dissipation without creating zones of stress concentration and micro-cracking which would have challenge micropermeability. Thereby, among the tested materials oxipatite is proposed as canal filling material and sealer in endodontics. Clinical Significance: Oxipatite could be considered a good candidate for root canal filling material and sealer due to its improved long-term sealing ability and to the advanced remineralization, and so to the enhanced energy dissipation achieved at the inner zone of the radicular dentin.This work was supported by the Ministry of Economy and Competitiveness (MINECO) and European Regional Development Fund (FEDER). Project MAT2017-85999-P MINECO/AEI/FEDER/UE

Hydroxyapatite-based cements induce different apatite formation in radicular dentin

Objectives. To investigate crystallinity and ultrastructure of the formed hydroxyapatite at radicular cervical and apical dentin after being treated with three different canal sealers. Methods. Cervical and apical root dentin surfaces were treated with two experimental hydroxyapatite-based sealers, containing sodium hydroxide (calcypatite) or zinc oxide (oxipatite) and an epoxy resin-based canal sealer (AH Plus); gutta-percha without sealer was included as control. Dentin surfaces were studied by X-ray diffraction and transmission electron microscopy through selected area diffraction and bright-field imaging after 24 h and 12 m of storage. Results. Root cervical dentin treated with calcypatite and oxipatite produced poor crystallinity of new minerals, wide amorphous phase and non-stoichiometry. Reflections at the 002 plane and the corresponding diffraction rings attained lower values in the Scherrer equation and the Scherrer-Wilson equation in samples treated with both HAp-based sealers than in specimens without sealer or with AH Plus. At root cervical dentin treated with calcypatite, shorter and wider crystallite size formations and lower crystals grain size were found, if compared to those encountered at oxipatite treated dentin. Oxipatite attained improved crystallographic atomic order and less structural variation in both distances and angles. Apical dentin treated with oxipatite attained preferred grain orientation with polycrystalline lattices. Significance. The immature crystallites formed in dentin treated with calcypatite and oxipatite will account for high hydroxyapatite solubility and remineralizing activity. New polycrystalline formations encountered in apical dentin treated with oxipatite may also produce high mechanical performance.This work was supported by the Ministry of Economy and Competitiveness (MINECO) and European Regional Development Fund (FEDER) Project MAT2017-85999-P

Polymeric nanoparticles for endodontic therapy

The effectiveness of novel polymeric nanoparticles (NPs) application in reducing dentin permeability and facilitating dentin remineralization after endodontic treatment was evaluated. The effect of undoped NPs, zinc, calcium and doxycycline-doped NPs (Zn-NPs, Ca-NPs and D-NPs, respectively) was tested in radicular dentin. A control group without NPs was included. Radicular dentin was assessed for fluid filtration. Dentin remineralization was analyzed by scanning and transmission electron microscopy, energy-dispersive analysis, AFM, Young´s modulus (Ei), Nano DMA, Raman, and X-Ray Diffraction analysis. Ca-NPs and Zn-NPs treated dentin exhibited the lowest microleakage with hermetically sealed dentinal tubules and a zinc-based salt generation onto dentin. Zn-NPs favored crystallinity and promoted the highest Ei and functional remineralization at the apical dentin, generating differences between the values of complex modulus among groups. Ca-NPs produced closure of tubules and porosities at the expense of a relative mineral amorphization, without creating zones of stress concentration. The highest sealing efficacy was obtained in Zn-NPs-treated samples, along with the highest values of Young´s modulus and dentin mineralization. These high values of Ei were obtained by closing voids, cracks, pores and tubules, and by strengthening the root dentin. When using undoped NPs or Ca-NPs, deposition of minerals occurred, but radicular dentin was not mechanically reinforced. Therefore, application of Zn-NPs in endodontically treated teeth previous to the canal filling is encouraged.This work was supported by the Ministry of Economy and Competitiveness and European Regional Development Fund [MAT2017-85999P MINECO/AEI/FEDER/UE]

Melatonin-doped polymeric nanoparticles induce high crystalline apatite formation in root dentin

This work was funded by the Ministry of Economy and Competitiveness and European Regional Development Fund( MINECO/AEI/FEDER/UE) Project number PID2020-114694RBI00. Funding for open access charge: University of Granada / CBUA.Objective. To investigate the effect of novel polymeric nanoparticles (NPs) doped with melatonin (ML) on nano-hardness, crystallinity and ultrastructure of the formed hydroxyapatite after endodontic treatment. Methods. Undoped-NPs and ML-doped NPs (ML-NPs) were tested at radicular dentin, after 24 h and 6 m. A control group without NPs was included. Radicular cervical and apical dentin surfaces were studied by nano-hardness measurements, X-ray diffraction and transmission electron microscopy. Mean and standard deviation were analyzed by ANOVA and StudentNewman-Keuls multiple comparisons (p < 0.05). Results. Cervical dentin treated with undoped NPs maintained its nano-hardness values after 6 m of storage being [24 h: 0.29 (0.01); 6 m: 0.30 (0.02) GPa], but it decreased at apical dentin [24 h: 0.36 (0.01); 6 m: 0.28 (0.02) GPa]. When ML-NPs were used, nano-hardness was similar over time [24h: 0.31 (0.02); 6 m: 0.28 (0.03) GPa], at apical dentin. Root dentin treated with ML-NPs produced, in general, high crystallinity of new minerals and thicker crystals than those produced in the rest of the groups. After 6 m, crystals became organized in randomly oriented polyhedral, square polygonal block-like apatite or drop-like apatite polycrystalline lattices when ML-NPs were used. Undoped NPs generated poor crystallinity, with preferred orientation of small crystallite and increased microstrain. Significance. New polycrystalline formations encountered in dentin treated with ML-NPs may produce structural dentin stability and high mechanical performance at the root. The decrease of mechanical properties over time in dentin treated without NPs indicates scarce remineralization potential, dentin demineralization and further potential degradation. The amorphous stage may provide high hydroxyapatite solubility and remineralizing activity.Ministry of Economy and Competitiveness and European Regional Development Fund( MINECO/AEI/FEDER/UE) PID2020-114694RB-I00University of Granada/CBU

Valoración de distintos tiempos de espera previos al sacrificio en corderos lechales sobre su comportamiento y varios parámetros sanguíneos indicadores de estrés

En 18 corderos lechales machos de 11-13 Kg de peso vivo de raza Lacaune, se han estudiado las repercusiones que tienen los tiempos de espera en matadero de 0, 3 y 6 horas sobre los parámetros de comportamiento indicadores del bienestar animal (de pie quieto o en movimiento, tumbado y número de veces que beben) y los parámetros plasmáticos indicadores de deshidratación (proteinas totales), de estrés físico (lactato) y de estrés psicológico (cortisol). Los corderos que permanecieron en la sala de espera (3 y 6 h) presentaron niveles significativamente más elevados (P < 0,01) de lactato que los sacrificados inmediatamente (0 h), como consecuencia de un mayor gasto energético. En relación a los parámetros de comportamiento los corderos estuvieron tumbados más tiempo en la sala de espera en las tres primeras horas que en las tres últimas (P< 0,001), sin diferencias significativas entre los lotes de 3 y 6 horas. Los resultados de este trabajo indican que el bienestar de los corderos lechales puede verse afectado por el tiempo de espera en el matadero, que debería ser mínimo.18 male suckling lambs 11-13 kg live weight of Lacaune breed have been studied in order to evaluate the impact of lairage time of 0, 3 and 6 hours at slaughterhouse: on the behavioural indicators of animal welfare (standing or moving, lying and number time of drinking) and plasma parameters of physical stress (lactate) and psychological stress (total protein and cortisol). Lambs housed in the lairage had significantly higher levels of lactate (

Effects of disease activity on lipoprotein levels in patients with early arthritis: can oxidized LDL cholesterol explain the lipid paradox theory?

Background An increased risk of cardiovascular (CV) complications has been described in patients with rheumatoid arthritis (RA). It is the result of the combined effect of classic CV risk factors and others that are specific to the disease. Methods We assessed data from 448 early arthritis (EA) patients: 79% women, age (median [p25-p75]) at onset: 55 [44?67] years and disease duration at study entry 5 [3?8] months; and 72% fulfilled the 1987 RA criteria at 2?years of follow-up. Rheumatoid factor was positive in 54% of patients and anti-citrullinated peptide antibodies in 50%. The follow-up of patients ranged from 2 to 5?years with more than 1400 visits with lipoprotein measurements available (mean 2.5 visits/patient). Demographic- and disease-related variables were systematically recorded. Total cholesterol (TC), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) levels were obtained from routine laboratory tests. Oxidized-LDL (oxLDL-C) levels were assessed using a commercial ELISA kit. We fitted population-averaged models nested by patient and visit to determine the effect of independent variables on serum levels of TC, its fractions, and oxLDL-C. Results After adjustment for several confounders, high-disease activity was significantly associated with decreased TC, HDL-C, and LDL-C levels and increased oxLDL-C levels. Standardized coefficients showed that the effect of disease activity was greater on oxLDL-C and HDL-C. Interestingly, we observed that those patients with lower levels of LDL-C showed higher oxLDL-C/LDL-C ratios. Conclusions High-disease activity in EA patients results in changes in the HDL-C and oxLDL-C levels, which in turn may contribute to the increased risk of CV disease observed in these patients.Our manuscript was supported by grants RD16/0011/0012, RD16/0011/0009, RD16/0011/0004, PI05/2044, and PI18/0371 from the Ministerio de Economía y Competitividad (Instituto de Salud Carlos III) and co-funded by Fondo Europeo de Desarrollo Regional (FEDER)

Development and validation of a multivariate predictive model for rheumatoid arthritis mortality using a machine learning approach

We developed and independently validated a rheumatoid arthritis (RA) mortality prediction model using the machine learning method Random Survival Forests (RSF). Two independent cohorts from Madrid (Spain) were used: the Hospital Cl&iacute;nico San Carlos RA Cohort (HCSC-RAC; training; 1,461 patients), and the Hospital Universitario de La Princesa Early Arthritis Register Longitudinal study (PEARL; validation; 280 patients). Demographic and clinical-related variables collected during the first two years after disease diagnosis were used. 148 and 21 patients from HCSC-RAC and PEARL died during a median follow-up time of 4.3 and 5.0&nbsp;years, respectively. Age at diagnosis, median erythrocyte sedimentation rate, and number of hospital admissions showed the higher predictive capacity. Prediction errors in the training and validation cohorts were 0.187 and 0.233, respectively. A survival tree identified five mortality risk groups using the predicted ensemble mortality. After 1 and 7 years of follow-up, time-dependent specificity and sensitivity in the validation cohort were 0.79&ndash;0.80 and 0.43&ndash;0.48, respectively, using the cut-off value dividing the two lower risk categories. Calibration curves showed overestimation of the mortality risk in the validation cohort. In conclusion, we were able to develop a clinical prediction model for RA mortality using RSF, providing evidence for further work on external validation

Polymorphisms in Human IL4, IL10, and TNF Genes Are Associated with an Increased Risk of Developing NSAID-Exacerbated Respiratory Disease

[EN]Background: The role of genetics in non-steroidal anti-inflammatory drugs (NSAID) exacerbated respiratory disease (NERD) is unclear, with different candidates involved, such as HLA genes, genes related to leukotriene synthesis, and cytokine genes. This study aimed to determine possible associations between 22 polymorphisms in 13 cytokine genes. Methods: We included 195 patients (85 with NERD and 110 with respiratory disease who tolerate NSAIDs) and 156 controls (non-atopic individuals without a history of asthma, nasal polyposis (NP), or NSAID hypersensitivity). Genotyping was performed by sequence-specific primer polymerase chain reaction (PCR-SSP). Amplicons were analyzed by horizontal gel electrophoresis in 2% agarose. Results: Significant differences in allele and genotype frequency distributions were found in TNF (rs1800629), IL4 (rs2243248 and rs2243250), and IL10 (rs1800896, rs1800871, and rs1800872) genes in patients with NSAID hypersensitivity. In all cases, the minor allele and the heterozygous genotype were more prevalent in NERD. An association of TNF rs1800629 SNP with respiratory disease in NSAID-tolerant patients was also found. Conclusions: Retrospectively recorded, we found strong associations of NERD with polymorphisms in IL4, IL10, and TNF genes, suggesting that these genes could be involved in the inflammatory mechanisms underlying NERD.Sociedad Española de Alergología e Inmunología Clínica; Fundación de Investigación Médica Caja de Burgos; Instituto de Salud Carlos III’s Thematic Network of Cooperative Research in Health-RETICS (Thematic network of research in health Asthma, Adverse and Allergic Reactions, ARADYAL)

Inter and intra molecular dynamics in poly(trimethylene 2,5-furanoate) as revealed by infrared and Broadband Dielectric Spectroscopies

9 pags., 9 figs., 2 tabs.Infrared spectroscopy (IR) and Broadband Dielectric Spectroscopy (BDS) experiments have been performed in poly(trimethylene 2,5-furanoate)(PTF) and poly(trimethylene terephthalate)(PTT) below their glass transition temperatures. The BDS experiments reveal a richer inter-molecular dynamic for PTT as characterized by a multimodal β relaxation in contrast with the monomodal one exhibited by PTF. The evolution with temperature of comparable IR absorption bands is very similar for PTF and PTT and shows small shifts in wavenumbers towards lower values, with exception of the band related to the stretching mode of the carbonyl group. In addition, a significant difference appears in the shape of the bands associated with the –C[dbnd]O stretching. While for PTT the absorption feature is comprised of a single component, that for PTF exhibits several components suggesting the presence of hydrogen bonds. This effect may be responsible for the monomodal shape of the β relaxation of PTF since a higher degree of intramolecular coupling between the furan ring and the rest of the monomer is expected. Density Functional Theory (DFT) calculations support the experimental results revealing that as temperature increases an increment of the syn conformations of the 2,5-furandicarboxylic acid (FDCA) moiety is likely to occur in the amorphous state. The energy gain from more stable anti to less stable syn isomers can be compensated by the formation of hydrogen bonds between interchain FDCA moieties in syn conformations. This effect may cause additional hindrance to the intermolecular dynamics of the dielectric β relaxation. It is conceivable that the hindrance exhibited by PTF in both intra and inter-molecular dynamics may play a role in the reduction of gas diffusion and permeability of PTF in comparison with PTT.Grants PID2019-107514 GB-I00/AEI/10.13039/501100011033 and PID2019-106125 GB-I00/AEI/10.13039/501100011033 funded by MCIN/AEI/10.13039/501100011033 and by “ ERDF A way of making Europe”. GS acknowledges grant RYC2020-029810-I funded by MCIN/ AEI/10.13039/501100011033 and by “ ESF Investing in your future”. SP would like to thank for financial support from the National Science Centre within project SONATA no 2018/31/D/ST8/00792.