Changes in functional network centrality underlie cognitive dysfunction and physical disability in multiple sclerosis.

BACKGROUND: Cognitive dysfunction in multiple sclerosis (MS) has a large impact on the quality of life and is poorly understood. OBJECTIVE: The aim of this study was to investigate functional network integrity in MS, and relate this to cognitive dysfunction and physical disability. METHODS: Resting state fMRI scans were included of 128 MS patients and 50 controls. Eigenvector centrality mapping (ECM) was applied, a graph analysis technique that ranks the importance of brain regions based on their connectivity patterns. Significant ECM changes were related to physical disability and cognitive dysfunction. RESULTS: In MS patients, ECM values were increased in bilateral thalamus and posterior cingulate (PCC) areas, and decreased in sensorimotor and ventral stream areas. Sensorimotor ECM decreases were related to higher EDSS (rho = -0.24, p = 0.007), while ventral stream decreases were related to poorer average cognition (rho = 0.23, p = 0.009). The thalamus displayed increased connectivity to sensorimotor and ventral stream areas. CONCLUSION: In MS, areas in the ventral stream and sensorimotor cortex appear to become less central in the entire functional network of the brain, which is associated with clinico-cognitive dysfunction. The thalamus, however, displays increased connectivity with these areas. These findings may aid in further elucidating the function of functional reorganization processes in MS.

Four-year clinical evaluation of a self-adhesive luting agent for ceramic inlays.

OBJECTIVES: The aim of this randomized controlled clinical trial was to evaluate the 4-year clinical performance of a self-adhesive resin cement, RelyX Unicem (3M ESPE), used for cementation of ceramic inlays. In addition, the influence of selectively acid-etching enamel prior to luting on the clinical performance of the restorations was assessed. METHODS: Sixty-two IPS Empress 2 inlays/onlays were placed in 31 patients by two experienced clinicians. The restorations were luted with RelyX Unicem with (=experimental group: E) or without (=control group: NE) prior enamel etching with phosphoric acid. At baseline, 6 months, and 1, 2, and 4 years after placement, the restorations were assessed by two calibrated investigators using modified USPHS criteria. Ten selected samples of each group were investigated under SEM regarding morphological changes at the cement-inlay interface. RESULTS: The recall rate at 4 years was 97%. Two restorations (1 E, 1 NE) were lost, and one (E) had to be replaced due to inlay and tooth fracture resulting in a survival rate of 95%. No significant differences between the experimental and control group were noticed regarding all criteria (McNemar, p < 0.05). An obvious deterioration in marginal integrity was observed after 4 years as only 5% (E = 7%; NE = 3%) of the restorations exhibited an excellent marginal adaptation. In 90% of the restorations small, still clinically acceptable marginal deficiencies were observed. SEM of the luting gap showed an increased wear of the RelyX Unicem cement over the 4-year period. CONCLUSIONS: The self-adhesive luting cement RelyX Unicem can be recommended for bonding of ceramic inlays/onlays. Additional selective enamel etching does not improve the clinical performance of the restorations within the 4-year period. CLINICAL RELEVANCE: The self-adhesive resin composite RelyX Unicem showed acceptable clinical performance after 4 years of clinical service.

A framework to integrate EEG-correlated fMRI and intracerebral recordings.

EEG-correlated functional MRI (EEG-fMRI) has been used to indicate brain regions associated with interictal epileptiform discharges (IEDs). This technique enables the delineation of the complete epileptiform network, including multifocal and deeply situated cortical areas. Before EEG-fMRI can be used as an additional diagnostic tool in the preoperative work-up, its added value should be assessed in relation to intracranial EEG recorded from depth electrodes (SEEG) or from the cortex (ECoG), currently the clinical standard. In this study, we propose a framework for the analysis of the SEEG data to investigate in a quantitative way whether EEG-fMRI reflects the same cortical areas as identified by the IEDs present in SEEG recordings. For that purpose, the data of both modalities were analyzed with a general linear model at the same time scale and within the same spatial domain. The IEDs were used as predictors in the model, yielding for EEG-fMRI the brain voxels that were related to the IEDs and, similarly for SEEG, the electrodes that were involved. Finally, the results of the regression analysis were projected on the anatomical MRI of the patients. To explore the usefulness of this quantitative approach, a sample of five patients was studied who both underwent EEG-fMRI and SEEG recordings. For clinical validation, the results of the SEEG analysis were compared to the standard visual review of IEDs in SEEG and to the identified seizure onset zone, the resected area, and outcome of surgery. SEEG analysis revealed a spatial pattern for the most frequent and dominant IEDs present in the data of all patients. The electrodes with the highest correlation values were in good concordance with the electrodes that showed maximal amplitude during those events in the SEEG recordings. These results indicate that the analysis of SEEG data at the time scale of EEG-fMRI, using the same type of regression model, is a promising way to validate EEG-fMRI data. In fact, the BOLD areas with a positive hemodynamic response function were closely related to the spatial pattern of IEDs in the SEEG recordings in four of the five patients. The areas of significant BOLD that were not located in the vicinity of depth electrodes, were mainly characterized by negative hemodynamic responses. Furthermore, the area with a positive hemodynamic response function overlapped with the resected area in three patients, while it was located at the edge of the resection area for one. To conclude, the results of this study encourage the application of EEG-fMRI to guide the implantation of depth electrodes as prerequisite for successful epilepsy surgery.

Graph theoretical analysis of magnetoencephalographic functional connectivity in Alzheimer's disease.

In this study we examined changes in the large-scale structure of resting-state brain networks in patients with Alzheimer's disease compared with non-demented controls, using concepts from graph theory. Magneto-encephalograms (MEG) were recorded in 18 Alzheimer's disease patients and 18 non-demented control subjects in a no-task, eyes-closed condition. For the main frequency bands, synchronization between all pairs of MEG channels was assessed using a phase lag index (PLI, a synchronization measure insensitive to volume conduction). PLI-weighted connectivity networks were calculated, and characterized by a mean clustering coefficient and path length. Alzheimer's disease patients showed a decrease of mean PLI in the lower alpha and beta band. In the lower alpha band, the clustering coefficient and path length were both decreased in Alzheimer's disease patients. Network changes in the lower alpha band were better explained by a 'Targeted Attack' model than by a 'Random Failure' model. Thus, Alzheimer's disease patients display a loss of resting-state functional connectivity in lower alpha and beta bands even when a measure insensitive to volume conduction effects is used. Moreover, the large-scale structure of lower alpha band functional networks in Alzheimer's disease is more random. The modelling results suggest that highly connected neural network 'hubs' may be especially at risk in Alzheimer's disease.

The effect of clinical experience on dentine bonding effectiveness: students versus trained dentists.

Clinical successful application of dentine adhesives depends not only on material-related but also on operator-related factors. The purpose of this study was to evaluate the dentine bonding effectiveness of a self-etch composite cement applied by operators with or without clinical experience under well-standardized, randomized and blind conditions. Forty-eight bovine dentine surfaces were randomly divided into two groups. The first group consisted of eight dental students with no clinical experience at all, and the second group consisted of eight dentists with extensive experience in adhesive dentistry (mean experience of 11.4 years). Next, a 4-mm-diameter stainless steel rod (SUS-304) was bonded to the dentine surface using Panavia Fluoro cement (Kuraray Medical Inc., Tokyo, Japan). After application procedures, the specimens were randomized and shear bond-strength measurements were performed by a single blinded operator. Mann-Whitney U test was used to determine statistical differences in bond strength between the two groups, and Kruskal-Wallis was used to determine statistical difference between the student and dentist groups. The means and standard deviations of bond strength were 11.5 +/- 8.1 MPa for the student group and 7.1 +/- 4.3 MPa for the dentist group, respectively. The bond strength of the student group was significantly higher than that of the dentist group. However, the variability in bond strength was significantly higher in the student group, and some specimens failed prior to actual testing (included as 0 MPa). Clinical experience did not have a positive effect on the bonding effectiveness of the self-etch composite cement to dentine.

Interactions between different EEG frequency bands and their effect on alpha-fMRI correlations.

In EEG/fMRI correlation studies it is common to consider the fMRI BOLD as filtered version of the EEG alpha power. Here the question is addressed whether other EEG frequency components may affect the correlation between alpha and BOLD. This was done comparing the statistical parametric maps (SPMs) of three different filter models wherein either the free or the standard hemodynamic response functions (HRF) were used in combination with the full spectral bandwidth of the EEG. EEG and fMRI were co-registered in a 30 min resting state condition in 15 healthy young subjects. Power variations in the delta, theta, alpha, beta and gamma bands were extracted from the EEG and used as regressors in a general linear model. Statistical parametric maps (SPMs) were computed using three different filter models, wherein either the free or the standard hemodynamic response functions (HRF) were used in combination with the full spectral bandwidth of the EEG. Results show that the SPMs of different EEG frequency bands, when significant, are very similar to that of the alpha rhythm. This is true in particular for the beta band, despite the fact that the alpha harmonics were discarded. It is shown that inclusion of EEG frequency bands as confounder in the fMRI-alpha correlation model has a large effect on the resulting SPM, in particular when for each frequency band the HRF is extracted from the data. We conclude that power fluctuations of different EEG frequency bands are mutually highly correlated, and that a multi frequency model is required to extract the SPM of the frequency of interest from EEG/fMRI data. When no constraints are put on the shapes of the HRFs of the nuisance frequencies, the correlation model looses so much statistical power that no correlations can be detected.

Induction of B cell unresponsiveness to noninherited maternal HLA antigens during fetal life.

Patients who have received many transfusions become highly sensitized and develop antibodies against almost all HLA alloantigens, so that finding a cross-match negative kidney donor is difficult. A survey of those patients showed that 50 percent did not form antibodies against the noninherited maternal HLA antigens. Apart from the obvious clinical implications, the data indicate that a human equivalent of murine neonatal or actively acquired tolerance has now been identified.

Non-linear registration improves statistical power to detect hippocampal atrophy in aging and dementia.

OBJECTIVE: To compare the performance of different methods for determining hippocampal atrophy rates using longitudinal MRI scans in aging and Alzheimer's disease (AD). BACKGROUND: Quantifying hippocampal atrophy caused by neurodegenerative diseases is important to follow the course of the disease. In dementia, the efficacy of new therapies can be partially assessed by measuring their effect on hippocampal atrophy. In radiotherapy, the quantification of radiation-induced hippocampal volume loss is of interest to quantify radiation damage. We evaluated plausibility, reproducibility and sensitivity of eight commonly used methods to determine hippocampal atrophy rates using test-retest scans. MATERIALS AND METHODS: Manual, FSL-FIRST, FreeSurfer, multi-atlas segmentation (MALF) and non-linear registration methods (Elastix, NiftyReg, ANTs and MIRTK) were used to determine hippocampal atrophy rates on longitudinal T1-weighted MRI from the ADNI database. Appropriate parameters for the non-linear registration methods were determined using a small training dataset (N = 16) in which two-year hippocampal atrophy was measured using test-retest scans of 8 subjects with low and 8 subjects with high atrophy rates. On a larger dataset of 20 controls, 40 mild cognitive impairment (MCI) and 20  AD patients, one-year hippocampal atrophy rates were measured. A repeated measures ANOVA analysis was performed to determine differences between controls, MCI and AD patients. For each method we calculated effect sizes and the required sample sizes to detect one-year volume change between controls and MCI (NCTRL_MCI) and between controls and AD (NCTRL_AD). Finally, reproducibility of hippocampal atrophy rates was assessed using within-session rescans and expressed as an average distance measure DAve, which expresses the difference in atrophy rate, averaged over all subjects. The same DAve was used to determine the agreement between different methods. RESULTS: Except for MALF, all methods detected a significant group difference between CTRL and AD, but none could find a significant difference between the CTRL and MCI. FreeSurfer and MIRTK required the lowest sample sizes (FreeSurfer: NCTRL_MCI = 115, NCTRL_AD = 17 with DAve = 3.26%; MIRTK: NCTRL_MCI = 97, NCTRL_AD = 11 with DAve = 3.76%), while ANTs was most reproducible (NCTRL_MCI = 162, NCTRL_AD = 37 with DAve = 1.06%), followed by Elastix (NCTRL_MCI = 226, NCTRL_AD = 15 with DAve = 1.78%) and NiftyReg (NCTRL_MCI = 193, NCTRL_AD = 14 with DAve = 2.11%). Manually measured hippocampal atrophy rates required largest sample sizes to detect volume change and were poorly reproduced (NCTRL_MCI = 452, NCTRL_AD = 87 with DAve = 12.39%). Atrophy rates of non-linear registration methods also agreed best with each other. DISCUSSION AND CONCLUSION: Non-linear registration methods were most consistent in determining hippocampal atrophy and because of their better reproducibility, methods, such as ANTs, Elastix and NiftyReg, are preferred for determining hippocampal atrophy rates on longitudinal MRI. Since performances of non-linear registration methods are well comparable, the preferred method would mostly depend on computational efficiency.

How does upper extremity Fugl-Meyer motor score relate to resting-state EEG in chronic stroke? A power spectral density analysis.

OBJECTIVE: We investigated the potential added value of high-density resting-state EEG by addressing differences with healthy individuals and associations with Fugl-Meyer motor assessment of the upper extremity (FM-UE) scores in chronic stroke. METHODS: Twenty-one chronic stroke survivors with initial upper limb paresis and eleven matched controls were included. Group differences regarding resting-state EEG parameters (Delta Alpha ratio (DAR) and pairwise-derived Brain Symmetry Index (BSI)) and associations with FM-UE were investigated, as well as lateralization of BSI and the value of different frequency bands. RESULTS: Chronic stroke survivors showed higher BSI compared to controls (p < 0.001), most pronounced in delta and theta frequency bands (p < 0.0001; p < 0.001). In the delta and theta band, BSI was significantly negatively associated with FM-UE (both p = 0.008) corrected for confounding factors. DAR showed no differences between groups nor association with FM-UE. Directional BSI showed increased power in the affected versus the unaffected hemisphere. CONCLUSIONS: Asymmetry in spectral power between hemispheres was present in chronic stroke, most pronounced in low frequencies and related to upper extremity motor function deficit. SIGNIFICANCE: BSI is related to motor impairment and higher in chronic stroke patients compared to healthy controls, suggesting that BSI may be a marker of selective motor control.

Inter-rater agreement in glioma segmentations on longitudinal MRI.

BACKGROUND: Tumor segmentation of glioma on MRI is a technique to monitor, quantify and report disease progression. Manual MRI segmentation is the gold standard but very labor intensive. At present the quality of this gold standard is not known for different stages of the disease, and prior work has mainly focused on treatment-naive glioblastoma. In this paper we studied the inter-rater agreement of manual MRI segmentation of glioblastoma and WHO grade II-III glioma for novices and experts at three stages of disease. We also studied the impact of inter-observer variation on extent of resection and growth rate. METHODS: In 20 patients with WHO grade IV glioblastoma and 20 patients with WHO grade II-III glioma (defined as non-glioblastoma) both the enhancing and non-enhancing tumor elements were segmented on MRI, using specialized software, by four novices and four experts before surgery, after surgery and at time of tumor progression. We used the generalized conformity index (GCI) and the intra-class correlation coefficient (ICC) of tumor volume as main outcome measures for inter-rater agreement. RESULTS: For glioblastoma, segmentations by experts and novices were comparable. The inter-rater agreement of enhancing tumor elements was excellent before surgery (GCI 0.79, ICC 0.99) poor after surgery (GCI 0.32, ICC 0.92), and good at progression (GCI 0.65, ICC 0.91). For non-glioblastoma, the inter-rater agreement was generally higher between experts than between novices. The inter-rater agreement was excellent between experts before surgery (GCI 0.77, ICC 0.92), was reasonable after surgery (GCI 0.48, ICC 0.84), and good at progression (GCI 0.60, ICC 0.80). The inter-rater agreement was good between novices before surgery (GCI 0.66, ICC 0.73), was poor after surgery (GCI 0.33, ICC 0.55), and poor at progression (GCI 0.36, ICC 0.73). Further analysis showed that the lower inter-rater agreement of segmentation on postoperative MRI could only partly be explained by the smaller volumes and fragmentation of residual tumor. The median interquartile range of extent of resection between raters was 8.3% and of growth rate was 0.22 mm/year. CONCLUSION: Manual tumor segmentations on MRI have reasonable agreement for use in spatial and volumetric analysis. Agreement in spatial overlap is of concern with segmentation after surgery for glioblastoma and with segmentation of non-glioblastoma by non-experts.

Inter-observer variation of hippocampus delineation in hippocampal avoidance prophylactic cranial irradiation.

BACKGROUND: Hippocampal avoidance prophylactic cranial irradiation (HA-PCI) techniques have been developed to reduce radiation damage to the hippocampus. An inter-observer hippocampus delineation analysis was performed and the influence of the delineation variability on dose to the hippocampus was studied. MATERIALS AND METHODS: For five patients, seven observers delineated both hippocampi on brain MRI. The intra-class correlation (ICC) with absolute agreement and the generalized conformity index (CIgen) were computed. Median surfaces over all observers' delineations were created for each patient and regional outlining differences were analysed. HA-PCI dose plans were made from the median surfaces and we investigated whether dose constraints in the hippocampus could be met for all delineations. RESULTS: The ICC for the left and right hippocampus was 0.56 and 0.69, respectively, while the CIgen ranged from 0.55 to 0.70. The posterior and anterior-medial hippocampal regions had most variation with SDs ranging from approximately 1 to 2.5 mm. The mean dose (Dmean) constraint was met for all delineations, but for the dose received by 1% of the hippocampal volume (D1%) violations were observed. CONCLUSION: The relatively low ICC and CIgen indicate that delineation variability among observers for both left and right hippocampus was large. The posterior and anterior-medial border have the largest delineation inaccuracy. The hippocampus Dmean constraint was not violated.

A study of the brain's resting state based on alpha band power, heart rate and fMRI.

Considering that there are several theoretical reasons why fMRI data is correlated to variations in heart rate, these correlations are explored using experimental resting state data. In particular, the possibility is discussed that the "default network", being a brain area that deactivates during non-specific general tasks, is a hemodynamic effect caused by heart rate variations. Of fifteen healthy controls ECG, EEG and fMRI were co-registered. Slice time dependent heart rate regressors were derived from the ECG data and correlated to fMRI using a linear correlation analysis where the impulse response is estimated from the data. It was found that in most subjects substantial correlations between heart rate variations and fMRI exist, both within the brain and at the ventricles. The brain areas with high correlation to heart rate are different from the "default network" and the response functions deviate from the canonical hemodynamic response function. Furthermore, a general negative correlation was found between heart beat intervals (reverse of heart rate) and alpha power. We interpret this finding by assuming that subject's state varies between drowsiness and wakefulness. Finally, given this large correlation, we re-examined the contribution of heart rate variations to earlier reported fMRI/alpha band correlations, by adding heart rate regressors as confounders. It was found that inclusion of these confounders most often had a negligible effect. From its strong correlation to alpha power, we conclude that the heart rate variations contain important physiological information about subject's resting state. However, it does not provide a full explanation of the behaviour of the "default network". Its application as confounder in fMRI experiments is a relatively small computational effort, but may have a substantial impact in paradigms where heart rate is controlled by the stimulus.

Influence of the chemical structure of functional monomers on their adhesive performance.

Functional monomers in adhesive systems can improve bonding by enhancing wetting and demineralization, and by chemical bonding to calcium. This study tested the hypothesis that small changes in the chemical structure of functional monomers may improve their bonding effectiveness. Three experimental phosphonate monomers (HAEPA, EAEPA, and MAEPA), with slightly different chemical structures, and 10-MDP (control) were evaluated. Adhesive performance was determined in terms of microtensile bond strength of 4 cements that differed only for the functional monomer. Based on the Adhesion-Decalcification concept, the chemical bonding potential was assessed by atomic absorption spectrophotometry of the dissolution rate of the calcium salt of the functional monomers. High bond strength of the adhesive cement corresponded to low dissolution rate of the calcium salt of the respective functional monomer. The latter is according to the Adhesion-Decalcification concept, suggestive of a high chemical bonding capacity. We conclude that the adhesive performance of an adhesive material depends on the chemical structure of the functional monomer.

The role of HEMA in one-step self-etch adhesives.

UNLABELLED: In spite of its high allergenic potential, 2-hydroxyethyl methacrylate (HEMA), a low-molecular-weight monomer, is frequently used in adhesives for its positive influence on the bond strength. In addition, the presence of HEMA in one-component one-step adhesives can prevent phase separation. OBJECTIVES: In search of improved bonding effectiveness, the 24-h bond strength of four experimental one-step self-etch adhesives with different concentrations of HEMA to bur-cut enamel and dentin was determined using a micro-tensile bond strength protocol. METHODS: The tested experimental adhesives (Exp-0, Exp-10, Exp-19 and Exp-36) only differed in their concentration of HEMA, which was 0, 10, 19 and 36%, respectively. With an increasing concentration of HEMA, the concentration of acetone was decreased. Besides bond strength, the adhesives were also examined by light-microscopy for phase separation. The interface was investigated by SEM and TEM. RESULTS: Regarding bond strength, Exp-10 performed best. Even though Exp-36 was the only adhesive formulation that did not exhibit phase separation on a glass plate, it yielded the lowest bond strength. Accordingly, droplets could be observed by SEM and TEM in the adhesive layers of all adhesives, except for Exp-36 on enamel. CONCLUSION: A small amount of HEMA (10%) improved the bond strength of a one-step self-etch adhesive. When added in higher concentrations, this beneficial effect of HEMA on the bond strength is lost due to increased osmosis, which resulted in many droplets; due to reduced polymerization conversion; and sub-optimal physico-mechanical properties of the resultant poly-HEMA containing adhesive interface.

Technique sensitivity of water-free one-step adhesives.

OBJECTIVES: All-in-one adhesives have been associated with water-related problems, such as phase-separation, polymerization-inhibition and reduced shelf life. In this study we investigated whether these problems could be avoided by a water-free self-etch adhesive that requires a 'wet-bonding' application procedure. Additionally, the technique-sensitivity of such a system was evaluated. METHODS: The micro-tensile bond strength (muTBS) of a water-free and a water-containing experimental one-step adhesive (EXP) bonded to either 'air-dried', 'blot-dried' or 'overwet' bur-cut enamel and dentin was determined. Likewise, the muTBS of a commercial water-free adhesive Absolute2 (Denstply-Sankin) was determined. The interfacial interaction of the adhesives was evaluated by SEM and TEM. RESULTS: In the blot-dried group, both water-free adhesives obtained the highest bond strength and the bond strength of the water-free EXP was comparable to that of the water-containing EXP bonded to an air-dried surface. When they were applied to overwet surfaces, the water-free adhesives tended towards a lower bond strength. This was partly attributed to the presence of phase-separation (or 'overwet') droplets in the adhesive layer. Unexpectedly, even on air-dried dentin, the water-free adhesives were able to demineralize dentin, however to a limited extent, hence impairing the bond strength. SIGNIFICANCE: Water-free one-step adhesives are a valuable alternative for conventional water-containing one-step adhesives. However, water-related problems in these adhesives are not ruled out, as they are eventually also mixed with water during the application procedure. As such, they partially fail to meet their objective. In addition, their bonding procedure, which involves 'wet bonding', is more technique-sensitive than dry bonding.

A randomized controlled clinical trial of a HEMA-free all-in-one adhesive in non-carious cervical lesions at 1 year.

OBJECTIVES: One-step self-etch adhesives are the most recent generation of adhesives introduced onto the market. The objective of this randomized controlled clinical trial was to test the hypothesis that a one-step self-etch adhesive performs equally well as a conventional three-step etch&rinse adhesive (gold standard). METHODS: Fifty-two patients had 267 non-carious cervical lesions restored with Gradia Direct Anterior (GC). These composite restorations were bonded either with the 'all-in-one' adhesive G-Bond (GC) or with the three-step etch&rinse adhesive Optibond FL (Kerr). The restorations were evaluated after 6 and 12 months clinical service regarding their retention, marginal integrity and discoloration, caries occurrence, preservation of tooth vitality and post-operative sensitivity. Retention loss, severe marginal defects and/or discoloration that needed intervention (repair or replacement) and the occurrence of caries were considered as clinical failures. A logistic regression analysis with generalized estimating equations was used to account for the clustered data (multiple restorations per patient). RESULTS: The recall rate at 1 year was 98%. The statistical analysis revealed a relatively low patient factor, indicating that supplementary information could be obtained from the additional restorations placed per patient. The retention rate for G-Bond was 98.5% compared to 99.3% for Optibond FL, due to the retention loss of two and one restorations, respectively. There were no significant differences between the two adhesives regarding the evaluated parameters except for the presence of small enamel marginal defects with G-Bond. CONCLUSIONS: After 12 months, the simplified one-step G-Bond and the three-step Optibond FL were clinically equally successful, even though both adhesives were characterized by progressive degradation of marginal adaptation, and G-Bond exhibited more small enamel marginal defects.

Do collagen cross-linkers improve dentin's bonding receptiveness?

OBJECTIVES: Dentin biomodification using collagen cross-linkers has been proposed as one of the strategies to improve bond durability of adhesives to dentin. However, literature is not very consistent regarding their benefit, in particular when cross-linkers are applied in clinically realistic application times. This study investigated the effect of three cross-linkers on the mini-interfacial fracture toughness (mini-iFT) of four adhesives bonded to dentin following either etch&rinse (E&R) or self-etch (SE) modes. METHODS: 60 molars were randomly divided in accordance with the three variables: cross-linker, adhesive and bonding mode (n=5). The cross-linkers glutaraldehyde (5wt%; GA), proanthocyanidin (6.5wt%; PA), or UVA-activated riboflavin (0.5wt%; RB), and distilled water (control) were applied on dentin for 60s after acid-etching (E&R) or before self-etching (SE). The 3-step E&R adhesive (3E&Ra) OptiBond FL (Kerr), the 2-step SE adhesive (2SEa) Clearfil SE Bond 2 (Kuraray Noritake) and the universal adhesives G-Premio Bond (GC) and Prime&Bond Active (Dentsply), the latter two employed in both E&R and SE modes, were applied following the respective manufacturer's instructions. Composite buildups (8×8×8mm) were made using Filtek Supreme XTE (3M) prior to 1-week storage in artificial saliva. After the teeth were sectioned into mini-specimens (1.5×2.0×18mm), a single notch was prepared at the adhesive-dentin interface. Half of the specimens were immediately loaded until failure by 4-point bending to determine the mini-iFT, while the remaining specimen set was tested upon 6-month aging. Data were statistically analyzed with a linear model (p<0.05). RESULTS: No significant decrease in mini-iFT was noted only for PA (p<0.05), while the mini-iFT decreased for both other cross-linkers and in quite a similar way as when solely water (Wa) was applied. SIGNIFICANCE: The cross-linker proanthocyanidin (PA) applied in clinically relevant conditions was able to maintain a stable mini-iFT after 6-month aging. The incorporation of UVA-activated riboflavin (RB) and glutaraldehyde (GA) in the dentin-bonding protocol appeared not effective to improve the stability of adhesive-dentin interfaces.

Benefits of Nonthermal Atmospheric Plasma Treatment on Dentin Adhesion.

OBJECTIVES:: This study aimed to evaluate the influence of two nonthermal atmospheric plasma (NTAP) application times and two storage times on the microtensile bond strength (µTBS) to dentin. The influence of NTAP on the mechanical properties of the dentin-resin interface was studied by analyzing nanohardness (NH) and Young's modulus (YM). Water contact angles of pretreated dentin and hydroxyapatite blocks were also measured to assess possible alterations in the surface hydrophilicity upon NTAP. METHODS AND MATERIALS:: Forty-eight human molars were used in a split-tooth design (n=8). Midcoronal exposed dentin was flattened by a 600-grit SiC paper. One-half of each dentin surface received phosphoric acid conditioning, while the other half was covered with a metallic barrier and remained unetched. Afterward, NTAP was applied on the entire dentin surface (etched or not) for 10 or 30 seconds. The control groups did not receive NTAP treatment. Scotchbond Universal (SBU; 3M ESPE) and a resin-based composite were applied to dentin following the manufacturer's instructions. After 24 hours of water storage at 37°C, the specimens were sectioned perpendicular to the interface to obtain approximately six specimens or bonded beams (approximately 0.9 mm2 in cross-sectional area) representing the etch-and-rinse (ER) approach and another six specimens representing the self-etch (SE) approach. Half of the µTBS specimens were immediately loaded until failure, while the other half were first stored in deionized water for two years. Three other bonded teeth were selected from each group (n=3) for NH and YM evaluation. Water contact-angle analysis was conducted using a CAM200 (KSV Nima) goniometer. Droplet images of dentin and hydroxyapatite surfaces with or without 10 or 30 seconds of plasma treatment were captured at different water-deposition times (5 to 55 seconds). RESULTS:: Two-way analysis of variance revealed significant differences in µTBS of SBU to dentin after two years of water storage in the SE approach, without differences among treatments. After two years of water aging, the ER control and ER NTAP 10-second groups showed lower µTBS means compared with the ER NTAP 30-second treated group. Nonthermal atmospheric plasma resulted in higher NH and YM for the hybrid layer. The influence of plasma treatment in hydrophilicity was more evident in the hydroxyapatite samples. Dentin hydrophilicity increased slightly after 10 seconds of NTAP, but the difference was higher when the plasma was used for 30 seconds. CONCLUSIONS:: Dentin NTAP treatment for 30 seconds contributed to higher µTBS after two years of water storage in the ER approach, while no difference was observed among treatments in the SE evaluation. This result might be correlated to the increase in nanohardness and Young's modulus of the hybrid layer and to better adhesive infiltration, since dentin hydrophilicity was also improved. Although some effects were observed using NTAP for 10 seconds, the results suggest that 30 seconds is the most indicated treatment time.

Artifact removal in co-registered EEG/fMRI by selective average subtraction.

OBJECTIVE: Co-registration of EEG (electroencephalogram) and fMRI (functional magnetic resonance imaging) remains a challenge due to the large artifacts induced on the EEG by the MR (magnetic resonance) sequence magnetic fields. Thus, we present an algorithm, based on the average-subtraction method, which is able to correct EEG data for gradient and pulse artifacts. METHODS: MR sequence timing parameters are estimated from the EEG data and both slice and volume artifact templates are subtracted from the data. A clustering algorithm is proposed to account for the variability of the pulse artifact. RESULTS: The algorithm is able to keep the spontaneous EEG as well as visual evoked potentials (VEPs), while removing gradient and pulse artifacts with only a subtraction of selectively averaged data. In the frequency domain, the artifact frequencies are strongly attenuated. Estimated MR sequence time parameters showed that the correction is extremely sensitive to the slice time value. Pulse artifact clustering showed that most of the variability is due to the time jitter of the pulse artifact markers. CONCLUSIONS: Selective subtraction of averages in combination with proper time alignment is enough to remove most of the MR-induced artifacts. SIGNIFICANCE: Clean EEG can be obtained from raw signals that are corrupted by MR-induced artifacts during simultaneous EEG-fMRI scanning without using dedicated hardware to synchronize EEG and fMRI clocks.

Origin of interfacial droplets with one-step adhesives.

Contemporary one-step self-etch adhesives are often documented with interfacial droplets. The objective of this study was to research the origin of these droplets. Two HEMA-rich and one HEMA-free adhesive were applied to enamel and dentin, with the lining composite either immediately cured or cured only after 20 min. All one-step adhesives exhibited droplets at the interface; however, the droplets had two different origins. With the HEMA-free adhesives, droplets were located throughout the adhesive layer and were stable in number over time. With the HEMA-rich adhesives, the droplets were observed exclusively at the adhesive resin/composite interface, and their number increased significantly when the composite was delay-cured. Only the latter droplets caused a significant drop in bond strength after delayed curing. While the droplets in the HEMA-free one-step adhesives should be ascribed to phase separation, those observed with HEMA-rich adhesives resulted from water absorption from dentin through osmosis.