Ions-modified nanoparticles affect functional remineralization and energy dissipation through the resin-dentin interface

The aim of this study was to evaluate changes in the mechanical and chemical behavior, and bonding ability at dentin interfaces infiltrated with polymeric nanoparticles (NPs) prior to resin application. Dentin surfaces were treated with 37% phosphoric acid followed by application of an ethanol suspension of NPs, Zn-NPs or Ca-NPs followed by the application of an adhesive, Single Bond (SB). Bonded interfaces were stored for 24 h, submitted to microtensile bond strength test, and evaluated by scanning electron microscopy. After 24 h and 21 d of storage, the whole resin-dentin interface adhesive was evaluated using a Nano-DMA. Complex modulus, storage modulus and tan delta (δ) were assessed. AFM imaging and Raman analysis were performed. Bond strength was not affected by NPs infiltration. After 21 d of storage, tan δ generally decreased at Zn-NPs/resin-dentin interface, and augmented when Ca-NPs or non-doped NPs were used. When both Zn-NPs and Ca-NPs were employed, the storage modulus and complex modulus decreased, though both moduli increased at the adhesive and at peritubular dentin after Zn-NPs infiltration. The phosphate and the carbonate peaks, and carbonate substitution, augmented more at interfaces promoted with Ca-NPs than with Zn-NPs after 21 d of storage, but crystallinity did not differ at created interfaces with both ions-doped NPs. Crosslinking of collagen and the secondary structure of collagen improved with Zn-NPs resin-dentin infiltration. Ca-NPs-resin dentin infiltration produced a favorable dissipation of energy with minimal stress concentration trough the crystalline remineralized resin-dentin interface, causing minor damage at this structure.This work was supported by the Ministry of Economy and Competitiveness (MINECO) [Project MAT2014-52036-P]

Nonparametric Covariate Adjustment for Receiver Operating Characteristic Curves

The accuracy of a diagnostic test is typically characterised using the receiver operating characteristic (ROC) curve. Summarising indexes such as the area under the ROC curve (AUC) are used to compare different tests as well as to measure the difference between two populations. Often additional information is available on some of the covariates which are known to influence the accuracy of such measures. We propose nonparametric methods for covariate adjustment of the AUC. Models with normal errors and non-normal errors are discussed and analysed separately. Nonparametric regression is used for estimating mean and variance functions in both scenarios. In the general noise case we propose a covariate-adjusted Mann-Whitney estimator for AUC estimation which effectively uses available data to construct working samples at any covariate value of interest and is computationally efficient for implementation. This provides a generalisation of the Mann-Whitney approach for comparing two populations by taking covariate effects into account. We derive asymptotic properties for the AUC estimators in both settings, including asymptotic normality, optimal strong uniform convergence rates and MSE consistency. The usefulness of the proposed methods is demonstrated through simulated and real data examples

Zinc-modified nanopolymers improve the quality of resin-dentin bonded interfaces

Introduction: Demineralized collagen fibers at the hybrid layer are susceptible to degradation. Remineralization may aid to improve bond longevity. Objectives: The aim of the present study was to infiltrate zinc and calcium-loaded polymeric nanoparticles into demineralized dentin to facilitate hybrid layer remineralization. Materials and methods: Zinc or calcium-loaded polymeric nanoparticles were infiltrated into etched dentin, and Single Bond Adhesive was applied. Bond strength was tested after 24 h and 6 months storage. Nanomechanical properties, dyeassisted confocal laser microscopy, and Masson’s trichrome staining evaluation were performed to assess for the hybrid layer morphology, permeability, and remineralization ability after 24 h and 3 months. Data were analyzed by ANOVA and Student–Newman–Keuls multiple comparisons tests (p < 0.05). Results: Immediate bond strength was not affected by nanoparticles infiltration (25 to 30 MPa), while after 6 months, bond strengths were maintained (22 to 24 MPa). After 3 months, permeability occurred only in specimens in which nanoparticles were not infiltrated. Dentin remineralization, at the bottom of the hybrid layer, was observed in all groups. After microscopy analysis, zinc-loaded nanoparticles were shown to facilitate calcium deposition throughout the entire hybrid layer. Young’s modulus at the hybrid layer increased from 2.09 to 3.25 GPa after 3 months, in specimens with zinc nanoparticles; meanwhile, these values were reduced from 1.66 to 0.49 GPa, in the control group. Conclusion: Infiltration of polymeric nanoparticles into demineralized dentin increased long-term bond strengths. Zinc-loaded nanoparticles facilitate dentin remineralization within the complete resin–dentin interface. Clinical relevance: Resin–dentin bond longevity and dentin remineralization at the hybrid layer were facilitated by zincloaded nanoparticles.This work was supported by a grant, MINECO/FEDER MAT2014-52036-P

Permanent 125I-seed prostate brachytherapy: early prostate specific antigen value as a predictor of PSA bounce occurrence

<p>Abstract</p> <p>Purpose</p> <p>To evaluate predictive factors for PSA bounce after ¹²⁵I permanent seed prostate brachytherapy and identify criteria that distinguish between benign bounces and biochemical relapses.</p> <p>Materials and methods</p> <p>Men treated with exclusive permanent ¹²⁵I seed brachytherapy from November 1999, with at least a 36 months follow-up were included. Bounce was defined as an increase ≥ 0.2 ng/ml above the nadir, followed by a spontaneous return to the nadir. Biochemical failure (BF) was defined using the criteria of the Phoenix conference: nadir +2 ng/ml.</p> <p>Results</p> <p>198 men were included. After a median follow-up of 63.9 months, 21 patients experienced a BF, and 35.9% had at least one bounce which occurred after a median period of 17 months after implantation (4-50). Bounce amplitude was 0.6 ng/ml (0.2-5.1), and duration was 13.6 months (4.0-44.9). In 12.5%, bounce magnitude exceeded the threshold defining BF. Age at the time of treatment and high PSA level assessed at 6 weeks were significantly correlated with bounce but not with BF. Bounce patients had a higher BF free survival than the others (100% versus 92%, p = 0,007). In case of PSA increase, PSA doubling time and velocity were not significantly different between bounce and BF patients. Bounces occurred significantly earlier than relapses and than nadir + 0.2 ng/ml in BF patients (17 vs 27.8 months, p < 0.0001).</p> <p>Conclusion</p> <p>High PSA value assessed 6 weeks after brachytherapy and young age were significantly associated to a higher risk of bounces but not to BF. Long delays between brachytherapy and PSA increase are more indicative of BF.</p

A Novel OxyR Sensor and Regulator of Hydrogen Peroxide Stress with One Cysteine Residue in Deinococcus radiodurans

In bacteria, OxyR is a peroxide sensor and transcription regulator, which can sense the presence of reactive oxygen species and induce antioxidant system. When the cells are exposed to H2O2, OxyR protein is activated via the formation of a disulfide bond between the two conserved cysteine residues (C199 and C208). In Deinococcus radiodurans, a previously unreported special characteristic of DrOxyR (DR0615) is found with only one conserved cysteine. dr0615 gene mutant is hypersensitive to H2O2, but only a little to ionizing radiation. Site-directed mutagenesis and subsequent in vivo functional analyses revealed that the conserved cysteine (C210) is necessary for sensing H2O2, but its mutation did not alter the binding characteristics of OxyR on DNA. Under oxidant stress, DrOxyR is oxidized to sulfenic acid form, which can be reduced by reducing reagents. In addition, quantitative real-time PCR and global transcription profile results showed that OxyR is not only a transcriptional activator (e.g., katE, drb0125), but also a transcriptional repressor (e.g., dps, mntH). Because OxyR regulates Mn and Fe ion transporter genes, Mn/Fe ion ratio is changed in dr0615 mutant, suggesting that the genes involved in Mn/Fe ion homeostasis, and the genes involved in antioxidant mechanism are highly cooperative under extremely oxidant stress. In conclusion, these findings expand the OxyR family, which could be divided into two classes: typical 2-Cys OxyR and 1-Cys OxyR

Review on catalytic cleavage of C-C inter-unit linkages in lignin model compounds: Towards lignin depolymerisation

Lignin depolymerisation has received considerable attention recently due to the pressing need to find sustainable alternatives to fossil fuel feedstock to produce chemicals and fuels. Two types of interunit linkages (C–C and C–O linkages) link several aromatic units in the structure of lignin. Between these two inter-unit linkages, the bond energies of C–C linkages are higher than that of C–O linkages, making them harder to break. However, for an efficient lignin depolymerisation, both types of inter-unit linkages have to be broken. This is more relevant because of the fact that many delignification processes tend to result in the formation of additional C–C inter-unit bonds. Here we review the strategies reported for the cleavage of C–C inter-unit linkages in lignin model compounds and lignin. Although a number of articles are available on the cleavage of C–O inter-unit linkages, reports on the selective cleavage of C–C inter-unit linkages are relatively less. Oxidative cleavage, hydrogenolysis, two-step redox-neutral process, microwave assisted cleavage, biocatalytic and photocatalytic methods have been reported for the breaking of C–C inter-unit linkages in lignin. Here we review all these methods in detail, focused only on the breaking of C–C linkages. The objective of this review is to motivate researchers to design new strategies to break this strong C–C inter-unit bonds to valorise lignins, technical lignins in particular

Protein tyrosine phosphatases expression during development of mouse superior colliculus

Protein tyrosine phosphatases (PTPs) are key regulators of different processes during development of the central nervous system. However, expression patterns and potential roles of PTPs in the developing superior colliculus remain poorly investigated. In this study, a degenerate primer-based reverse transcription-polymerase chain reaction (RT-PCR) approach was used to isolate seven different intracellular PTPs and nine different receptor-type PTPs (RPTPs) from embryonic E15 mouse superior colliculus. Subsequently, the expression patterns of 11 PTPs (TC-PTP, PTP1C, PTP1D, PTP-MEG2, PTP-PEST, RPTPJ, RPTPε, RPTPRR, RPTPσ, RPTPκ and RPTPγ) were further analyzed in detail in superior colliculus from embryonic E13 to postnatal P20 stages by quantitative real-time RT-PCR, Western blotting and immunohistochemistry. Each of the 11 PTPs exhibits distinct spatiotemporal regulation of mRNAs and proteins in the developing superior colliculus suggesting their versatile roles in genesis of neuronal and glial cells and retinocollicular topographic mapping. At E13, additional double-immunohistochemical analysis revealed the expression of PTPs in collicular nestin-positive neural progenitor cells and RC-2-immunoreactive radial glia cells, indicating the potential functional importance of PTPs in neurogenesis and gliogenesis

The Impact of Entrepreneurship Education in Higher Education: A Systematic Review and Research Agenda

Using a teaching model framework, we systematically review empirical evidence on the impact of entrepreneurship education (EE) in higher education on a range of entrepreneurial outcomes, analyzing 159 published articles from 2004 to 2016. The teaching model framework allows us for the first time to start rigorously examining relationships between pedagogical methods and specific outcomes. Reconfirming past reviews and meta-analyses, we find that EE impact research still predominantly focuses on short-term and subjective outcome measures and tends to severely underdescribe the actual pedagogies being tested. Moreover, we use our review to provide an up-to-date and empirically rooted call for less obvious, yet greatly promising, new or underemphasized directions for future research on the impact of university-based entrepreneurship education. This includes, for example, the use of novel impact indicators related to emotion and mind-set, focus on the impact indicators related to the intention-to-behavior transition, and exploring the reasons for some contradictory findings in impact studies including person-, context-, and pedagogical model-specific moderator

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Spontaneous Breathing in Early Acute Respiratory Distress Syndrome: Insights From the Large Observational Study to UNderstand the Global Impact of Severe Acute Respiratory FailurE Study

OBJECTIVES: To describe the characteristics and outcomes of patients with acute respiratory distress syndrome with or without spontaneous breathing and to investigate whether the effects of spontaneous breathing on outcome depend on acute respiratory distress syndrome severity. DESIGN: Planned secondary analysis of a prospective, observational, multicentre cohort study. SETTING: International sample of 459 ICUs from 50 countries. PATIENTS: Patients with acute respiratory distress syndrome and at least 2 days of invasive mechanical ventilation and available data for the mode of mechanical ventilation and respiratory rate for the 2 first days. INTERVENTIONS: Analysis of patients with and without spontaneous breathing, defined by the mode of mechanical ventilation and by actual respiratory rate compared with set respiratory rate during the first 48 hours of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Spontaneous breathing was present in 67% of patients with mild acute respiratory distress syndrome, 58% of patients with moderate acute respiratory distress syndrome, and 46% of patients with severe acute respiratory distress syndrome. Patients with spontaneous breathing were older and had lower acute respiratory distress syndrome severity, Sequential Organ Failure Assessment scores, ICU and hospital mortality, and were less likely to be diagnosed with acute respiratory distress syndrome by clinicians. In adjusted analysis, spontaneous breathing during the first 2 days was not associated with an effect on ICU or hospital mortality (33% vs 37%; odds ratio, 1.18 [0.92-1.51]; p = 0.19 and 37% vs 41%; odds ratio, 1.18 [0.93-1.50]; p = 0.196, respectively ). Spontaneous breathing was associated with increased ventilator-free days (13 [0-22] vs 8 [0-20]; p = 0.014) and shorter duration of ICU stay (11 [6-20] vs 12 [7-22]; p = 0.04). CONCLUSIONS: Spontaneous breathing is common in patients with acute respiratory distress syndrome during the first 48 hours of mechanical ventilation. Spontaneous breathing is not associated with worse outcomes and may hasten liberation from the ventilator and from ICU. Although these results support the use of spontaneous breathing in patients with acute respiratory distress syndrome independent of acute respiratory distress syndrome severity, the use of controlled ventilation indicates a bias toward use in patients with higher disease severity. In addition, because the lack of reliable data on inspiratory effort in our study, prospective studies incorporating the magnitude of inspiratory effort and adjusting for all potential severity confounders are required