Effect of Cangrelor on Infarct Size in ST-Segment-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (The PITRI Trial).

BACKGROUND: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention. METHODS: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore. Patients were randomized to receive either cangrelor or placebo initiated before the primary percutaneous coronary intervention procedure on top of oral ticagrelor. The key exclusion criteria included presenting <6 hours of symptom onset; previous MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance. The primary efficacy end point was acute MI size by cardiovascular magnetic resonance within the first week expressed as percentage of the left ventricle mass (%LVmass). Microvascular obstruction was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety end point was Bleeding Academic Research Consortium-defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test (reported as median [first quartile-third quartile]), and categorical variables were compared by Fisher exact test. A 2-sided P<0.05 was considered statistically significant. RESULTS: Of 209 recruited patients, 164 patients (78%) completed the acute cardiovascular magnetic resonance scan. There were no significant differences in acute MI size (placebo, 14.9% [7.3-22.6] %LVmass versus cangrelor, 16.3 [9.9-24.4] %LVmass; P=0.40) or the incidence (placebo, 48% versus cangrelor, 47%; P=0.99) and extent of microvascular obstruction (placebo, 1.63 [0.60-4.65] %LVmass versus cangrelor, 1.18 [0.53-3.37] %LVmass; P=0.46) between placebo and cangrelor despite a 2-fold decrease in platelet reactivity with cangrelor. There were no Bleeding Academic Research Consortium-defined major bleeding events in either group in the first 48 hours. CONCLUSIONS: Cangrelor administered at the time of primary percutaneous coronary intervention did not reduce acute MI size or prevent microvascular obstruction in patients with ST-segment-elevation MI given oral ticagrelor despite a significant reduction of platelet reactivity during the percutaneous coronary intervention procedure. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03102723.

Hysteresis and fiscal stimulus in a recession.

The COVID-19 pandemic initiated a deep global recession, and with interest rates at very low levels, warrants consideration of the efficacy of different forms of fiscal stimulus in response. History reveals that deep recessions may cause output and total factor productivity (TFP) hysteresis, a permanent or highly persistent fall in the levels of output and TFP relative to pre-recession trends. This article analyses the output and welfare multipliers of fiscal stimulus during a recession using a macro model with TFP and output hysteresis. We find that transfer payments, public consumption and investment all have high output and welfare multipliers due to their positive effects on TFP in a recessionary environment. However, public investment has the highest output and welfare multipliers, because it has a more positive impact on labour productivity due to the increase in the public capital stock.

Evaluation of the efficacy of calcium silicate vs. glass ionomer cement indirect pulp capping and restoration assessment criteria: a randomised controlled clinical trial-2-year results.

OBJECTIVES: Assess calcium silicate cement (Biodentine™) vs. glass ionomer cement (Fuji IX™, control) as indirect pulp capping (IPC) materials in patients with reversible pulpitis after a 2-year follow-up. Evaluate the integrity of the overlying resin composite restorations using modified USPHS criteria and FDI criteria. Investigate the sensitivity of the modified USPHS criteria compared to the FDI criteria in the assessment of the restorations. MATERIALS AND METHODS: Seventy-two restorations (36 Biodentine™, 36 Fuji IX™) were placed randomly in 53 patients. Periapical radiographs were taken at pre-treatment (T0), 12-month (T12), and 24-month (T24) review. Restorations were assessed using the modified USPHS and FDI criteria at T12 and T24. RESULTS: At 24 months, 15 teeth had failed to maintain vitality (6 Biodentine™, 9 Fuji IX™). Clinical success rate of IPC for both materials was 72% and is related to the intensity of reversible pulpitis symptoms. No difference was found between T12 and T24 in the periapical (PA) radiographs and in the integrity of the resin composite restorations overlying Biodentine™ compared to Fuji IX™. There was no difference in the efficacy of the USPHS criteria compared to the FDI criteria in the assessment of the resin composite restorations. CONCLUSIONS: Biodentine™ and Fuji IX™ were clinically effective when used as IPC materials in teeth with reversible pulpitis at T24. Resin composite restorations overlying both materials performed well at T24. Using the USPHS or FDI criteria is equally efficient at T24; however, longer term follow-up is needed to establish whether there are sensitivity differences between these assessment criteria. CLINICAL SIGNIFICANCE: Teeth with deep carious lesions approaching the pulp and with signs of reversible pulpitis can be treated successfully by indirect pulp capping using either Biodentine™ or Fuji IX™. Using the USPHS or FDI criteria to assess restorations is equally effective at 2 years. TRIAL REGISTRATION: NCT02201641.

Influence of bioactive particles on the chemical-mechanical properties of experimental enamel resin infiltrants.

OBJECTIVE: This study aimed at evaluating the chemophysical properties of experimental resin infiltrants (ERIs) doped with different bioactive particles. METHODS: A control resin infiltrant (CR) was formulated using triethylene glycol dimethacrylate (TEGDMA) and ethoxylated bisphenol A dimethacrylate (BisEMA). Moreover, five experimental ERIs were also created by incorporating the following bioactive fillers (10 wt%) into the CR: hydroxyapatite (Hap), amorphous calcium phosphate (ACP), zinc-polycarboxylated bioactive glass (BAG-Zn), bioactive glass 45S5 (BAG 45S5), and calcium silicate modified with beta tricalcium phosphate (ß-TCP). ICON® resin infiltrant was also used as control. All the ERIs used in this study were assessed for degree of conversion (DC), Knoop microhardness (KHN), softening ratio (SR), tensile cohesive strength (TCS), modulus of elasticity (E-modulus), water sorption (WS), and solubility (SL). Data were subjected to ANOVA and Tukey's test (α = 5%). RESULTS: ICON® presented the lowest DC, KHN, TCS, E-modulus, and SR. Incorporation of bioactive fillers into CR caused significant increase in the KHN. Conversely, no significant effect was observed on DC, TCS, and E-modulus. The resin infiltrant containing Hap showed a significant increase in softening ratio, while, ICON® presented the highest WS and SL. The WS of ACP-doped resin infiltrant was significantly higher than that of the Hap-doped infiltrant. The SL of the ACP-doped infiltrant was higher than CR BAG-Zn or BAG 45S5. CONCLUSION: The incorporation of bioactive particles into experimental resin infiltrants can improve the chemomechanical properties and reduce water sorption and solubility. CLINICAL RELEVANCE: Resin infiltrants doped with bioactive particles may improve the long-term performance of the treatment of white-spot lesions.

An in vitro investigation of pre-treatment effects before fissure sealing.

BACKGROUND: Fissure sealants prevent occlusal caries in permanent molars. Enamel preparation methods are used before fissure sealing. AIMS: To investigate effects of bioglass air-abrasion pre-treatment with and without an adhesive, on fissure enamel of permanent teeth, with respect to etchability, microleakage and microtensile bond strength. DESIGN: Half of the occlusal surfaces of 50 extracted premolars underwent bioglass air-abrasion. Dye was applied to the entire occlusal surface. Photographs were taken to score etched surface by dye uptake. Adhesive was applied to 25 of the bioglass-treated areas and all teeth were fissure sealed, sectioned, and evaluated using confocal microscopy. Buccal and lingual surfaces of a further eight premolars were acid-etched and randomly received: air-abrasion, adhesive, both, or none before sealant application for microtensile bond strength measurement in half of the samples immediately and half following 6 months of water immersion. RESULTS: Linear mixed models and multinomial logistic regression were used (P = 0.05). Bioglass air-abrasion significantly improved enamel etchability and reduced microleakage. The addition of an adhesive made no difference to either microleakage or microtensile bond strength. The combination of bioglass abrasion and adhesive led to more cohesive, rather than adhesive, failure. CONCLUSIONS: Bioglass air-abrasion improved enamel etchability and reduced microleakage irrespective of the adhesive use but neither pre-treatment affected the microtensile bond strength.

Drug-Coated Balloons: A Safe and Effective Alternative to Drug-Eluting Stents in Small Vessel Coronary Artery Disease.

BACKGROUND: Drug-coated balloons (DCB) have been used to treat de novo small vessel coronary disease (SVD), with promising results and shorter dual antiplatelet therapy (DAPT) duration compared to drug-eluting stents (DES). We compared safety and effectiveness of the two treatments at 1 year. METHODS: We reviewed 3,613 angioplasty cases retrospectively from 2011 to 2013 and identified 335 patients with SVD treated with device diameter of ≤2.5 mm. DCB-only angioplasty was performed in 172 patients, whereas 163 patients were treated with second-generation DES. RESULTS: DCB patients had smaller reference vessel diameter (2.22 ± 0.30 vs. 2.44 ± 0.19 mm, P < 0.001) and received smaller devices (median diameter 2.25 vs. 2.50 mm, P < 0.001) compared to the DES group. DES-treated vessels had larger acute lumen gain (1.71 ± 0.48 mm) than DCB (1.00 ± 0.53 mm, P < 0.001). Half the patients had diabetes mellitus. While there were more patients presenting with acute coronary syndrome (ACS) in the DCB group (77.9% vs. 62.2%, P = 0.013), they received shorter DAPT (7.4 ± 4.7 vs. 11.8 ± 1.4 months, P < 0.001) than the DES group. The 1-year composite major adverse cardiac event rate was 11.6% in the DCB arm and 11.7% in the DES arm (P = 1.000), with target lesion revascularization rate of 5.2% and 3.7%, respectively, (P = 0.601). CONCLUSIONS: In this high-risk cohort of patients, DCB-only angioplasty delivered good clinical outcome at 1 year. The results were comparable with DES-treated patients, but had the added benefit of a shorter DAPT regime.

An Analysis of Spatial Clustering of Stroke Types, In-hospital Mortality, and Reported Risk Factors in Alberta, Canada, Using Geographic Information Systems.

BACKGROUND: Despite advances in the quality and delivery of stroke care, regional disparities in stroke incidence and outcome persist. Spatial analysis using geographic information systems (GIS) can assist in identifying high-risk populations and regional differences in efficacy of stroke care. The aim of this study was to identify and locate geographic clusters of high or low rates of stroke, risk factors, and in-hospital mortality across a provincial health care network in Alberta, Canada. METHODS: This study employed a spatial epidemiological approach using population-based hospital administrative data. Getis-Ord Gi* and Spatial Scan statistics were used to identify and locate statistically significant "hot" and "cold" spots of stroke occurrence by type, risk factors, and in-hospital mortality. RESULTS: Marked regional variations were found. East central Alberta was a significant hot spot for ischemic stroke (relative risk [RR] 1.43, p<0.001), transient ischemic attack (RR 2.25, p<0.05), and in-hospital mortality (RR 1.50, p<0.05). Hot spots of intracerebral hemorrhage (RR 1.80, p<0.05) and subarachnoid hemorrhage (RR 1.64, p<0.05) were identified in a major urban centre. Unexpectedly, stroke risk factor hot spots (RR 2.58, p<0.001) were not spatially associated (did not overlap) with hot spots of ischemic stroke, transient ischemic attack, or in-hospital mortality. CONCLUSIONS: Integration of health care administrative data sets with geographic information systems contributes valuable information by identifying the existence and location of regional disparities in the spatial distribution of stroke occurrence and outcomes. Findings from this study raise important questions regarding why regional differences exist and how disparities might be mitigated.

Penetration depth of monomer systems into acrylic resin denture teeth used as pontics.

STATEMENT OF PROBLEM: The ways of softening and dissolving the surface of acrylic resin denture teeth need to be specified to obtain more durable prosthetic treatments that include resin denture teeth. PURPOSE: The purpose of this study was to analyze the penetration depth of 4 monomer systems applied during different exposure times on the acrylic resin denture teeth used as pontics of directly fabricated fiber-reinforced composite fixed dental prostheses. The penetration depth contributes to the adhesion of the tooth to the adhesive resin. MATERIAL AND METHODS: Ninety-six specimens were divided into 3 groups according to the acrylic resin denture tooth used: Artic 8 (Heraeus Kultzer), experimental tooth (GC), and Vitapan (Vita). Each group was divided into 4 subgroups according to the monomer system used: methylmethacrylate (99%), composite primer, a flowable composite resin, and a photopolymerizing dimethacrylate resin. The 4 monomer systems were labeled with rhodamine B to determine their penetration depth into the acrylic resin denture teeth. After exposure times of 1, 5, 15, and 60 minutes, the monomers were photopolymerized for 5 minutes, with the exception of methylmethacrylate. The specimens were cut orthogonally from gingival to occlusal in 4 slices (n=8/subgroup). The penetration depths of monomers were measured by a confocal scanning type microscope. Differences in the penetration depths were evaluated with ANOVA. RESULTS: ANOVA (R(2)=.699) revealed significant differences in the penetration depths according to the exposure times (P<.001), monomers (P<.001), brands used (P=.047), and their mutual interaction (P<.001). CONCLUSIONS: The ability of monomers to penetrate the surface of acrylic resin denture teeth was influenced by the monomer systems, which might improve the bond between the pontics and the fiber-reinforced composite frameworks of fixed dental prostheses.

How to do it?: percutaneous treatment of a severely stenosed and calcified left main stem bifurcation.

CASE SUMMARY: A frail 87 year-old lady presented with rest angina associated with widespread ECG change and troponin release. She failed attempts at medical therapy and therefore was referred for coronary intervention on the basis that she was not a surgical candidate. INVESTIGATION: Coronary angiography demonstrated heavily calcified coronary arteries with critical disease at the distal left main stem bifurcation extending into the proximal segments of both LAD and circumflex. DIAGNOSIS: Acute coronary syndrome with extensive calcific coronary artery disease in the left main stem bifurcation. MANAGEMENT: Sequential rotational atherectomy of the left main stem bifurcation followed by 'Y'-stenting using three Xience Prime drug eluting stents.

From metagenomes to metabolism: Systematically assessing the metabolic flux feasibilities for "Candidatus Accumulibacter" species during anaerobic substrate uptake.

With the rapid growing availability of metagenome assembled genomes (MAGs) and associated metabolic models, the identification of metabolic potential in individual community members has become possible. However, the field still lacks an unbiassed systematic evaluation of the generated metagenomic information to uncover not only metabolic potential, but also feasibilities of these models under specific environmental conditions. In this study, we present a systematic analysis of the metabolic potential in species of "Candidatus Accumulibacter", a group of polyphosphate-accumulating organisms (PAOs). We constructed a metabolic model of the central carbon metabolism and compared the metabolic potential among available MAGs for "Ca. Accumulibacter" species. By combining Elementary Flux Modes Analysis (EFMA) with max-min driving force (MDF) optimization, we obtained all possible flux distributions of the metabolic network and calculated their individual thermodynamic feasibility. Our findings reveal significant variations in the metabolic potential among "Ca. Accumulibacter" MAGs, particularly in the presence of anaplerotic reactions. EFMA revealed 700 unique flux distributions in the complete metabolic model that enable the anaerobic uptake of acetate and its conversion into polyhydroxyalkanoates (PHAs), a well-known phenotype of "Ca. Accumulibacter". However, thermodynamic constraints narrowed down this solution space to 146 models that were stoichiometrically and thermodynamically feasible (MDF > 0 kJ/mol), of which only 8 were strongly feasible (MDF > 7 kJ/mol). Notably, several novel flux distributions for the metabolic model were identified, suggesting putative, yet unreported, functions within the PAO communities. Overall, this work provides valuable insights into the metabolic variability among "Ca. Accumulibacter" species and redefines the anaerobic metabolic potential in the context of phosphate removal. More generally, the integrated workflow presented in this paper can be applied to any metabolic model obtained from a MAG generated from microbial communities to objectively narrow the expected phenotypes from community members.

Sweet Secrets: Exploring Novel Glycans and Glycoconjugates in the Extracellular Polymeric Substances of "Candidatus Accumulibacter".

Biological wastewater treatment relies on microorganisms that grow as flocs, biofilms, or granules for efficient separation of biomass from cleaned water. This biofilm structure emerges from the interactions between microbes that produce, and are embedded in, extracellular polymeric substances (EPS). The true composition and structure of the EPS responsible for dense biofilm formation are still obscure. We conducted a bottom-up approach utilizing advanced glycomic techniques to explore the glycan diversity in the EPS from a highly enriched "Candidatus Accumulibacter" granular sludge. Rare novel sugar monomers such as N-Acetylquinovosamine (QuiNAc) and 2-O-Methylrhamnose (2-OMe-Rha) were identified to be present in the EPS of both enrichments. Further, a high diversity in the glycoprotein structures of said EPS was identified by means of lectin based microarrays. We explored the genetic potential of "Ca. Accumulibacter" high quality metagenome assembled genomes (MAGs) to showcase the shortcoming of top-down bioinformatics based approaches at predicting EPS composition and structure, especially when dealing with glycans and glycoconjugates. This work suggests that more bottom-up research is necessary to understand the composition and complex structure of EPS in biofilms since genome based inference cannot directly predict glycan structures and glycoconjugate diversity.

The ICV sign as a marker of increased cerebral blood transit time.

OBJECTIVE/BACKGROUND: We describe the internal cerebral vein (ICV) sign, which is a hypo-opacification of the ICV on computed tomogram angiography (CTA) as a new marker of increased cerebral blood transit-time in ipsilateral internal carotid artery occlusions (ICAO). METHODS: A retrospective analysis of 153 patients with acute unilateral M1 middle cerebral artery (MCA) occlusions ± ICAOs was performed. The degree of contrast opacification of the ICV on the ipsilesional side was compared to that of the unaffected side. RESULTS: Of 153 patients in our study, 135 had M1 MCA occlusions ± intra-cranial ICAO (M1±iICAO) and 18 had isolated extracranial ICAO (eICAO). In the patients with proximal M1±iICAO, 57/65 (87.1%) showed the ICV sign. Of the 8 patients without the ICV sign in this group, 6 had prominent lenticulostriate arteries arising from the non-occluded M1 segment, 1 had a recurrent artery of Huebner, and 1 had filling of distal ICA/M1 segment through prominent Circle of Willis collaterals. For the 70 patients with isolated distal M1±iICAO, 7/70 (10%) showed the ICV sign, with all 7 showing occluded lenticulostriate arteries. Of the patients with eICAO, 8/18 showed the ICV sign, all 8 with the ICV sign had poor Circle of Willis collaterals. CONCLUSIONS: The ICV sign correlates well with presence of proximal M1±iICAO in patients with either occluded lenticulostriate arteries or poor Circle of Willis collaterals. In patients with eICAO, the sign correlates with reduced Circle of Willis collaterals and may be a marker of increased ipsilateral cerebral blood transit time.

Tissue Window in Stroke Thrombolysis study (TWIST): a safety study.

BACKGROUND: Stroke thrombolysis is limited by the "last-seen well" principle, which defines stroke onset time. A significant minority of stroke patients (~15%) awake with their symptoms and are by definition ineligible for thrombolysis because they were "last-seen well" at the time they went to bed implying an interval that is most often greater than three hours. METHODS: A single-centre prospective, safety study was designed to thrombolyse 20 subjects with stroke-on-awakening. Patients were eligible for inclusion if they were last seen well less than 12 hours previously, specifically including those who awoke from sleep with their stroke deficits. They had a baseline computed tomogram (CT) scan with an ASPECTS score greater than 5, no evidence of well-evolved infarction and a CT angiogram / Trans-cranial Doppler ultrasound study demonstrating an intracranial arterial occlusion. Patients fulfilled all other standard criteria for stroke thrombolysis. The primary outcome was safety defined by symptomatic ICH or death. RESULTS: Among 89 screened patients, 20 were treated with thrombolysis. Two patients (10%) died due to massive carotid territory stroke and two patients (10%) died of stroke complications. Two patients (10%) showed asymptomatic intracerebral hemorrhage (ICH) (petechial hemorrhage) and none symptomatic ICH. Reasons for exclusion were: (a) ASPECTS ≤ 5 (29); (b) well-evolved infarcts on CT (19); (c) historical mRS > 2 (17); (d) no demonstrable arterial occlusion or were too mild to warrant treatment (10). CONCLUSIONS: Patients who awake with their deficits can be safely treated with thrombolysis based upon a tissue window defined by NCCT and CTA/TCD.

Predicting the impact of temperature on metabolic fluxes using resource allocation modelling: Application to polyphosphate accumulating organisms.

The understanding of microbial communities and the biological regulation of its members is crucial for implementation of novel technologies using microbial ecology. One poorly understood metabolic principle of microbial communities is resource allocation and biosynthesis. Resource allocation theory in polyphosphate accumulating organisms (PAOs) is limited as a result of their slow imposed growth rate (typical sludge retention times of at least 4 days) and limitations to quantify changes in biomass components over a 6 hours cycle (less than 10% of their growth). As a result, there is no direct evidence supporting that biosynthesis is an exclusive aerobic process in PAOs that alternate continuously between anaerobic and aerobic phases. Here, we apply resource allocation metabolic flux analysis to study the optimal phenotype of PAOs over a temperature range of 4 °C to 20 °C. The model applied in this research allowed to identify optimal metabolic strategies in a core metabolic model with limited constraints based on biological principles. The addition of a constraint limiting biomass synthesis to be an exclusive aerobic process changed the metabolic behaviour and improved the predictability of the model over the studied temperature range by closing the gap between prediction and experimental findings. The results validate the assumption of limited anaerobic biosynthesis in PAOs, specifically "Candidatus Accumulibacter" related species. Interestingly, the predicted growth yield was lower, suggesting that there are mechanistic barriers for anaerobic growth not yet understood nor reflected in the current models of PAOs. Moreover, we identified strategies of resource allocation applied by PAOs at different temperatures as a result of the decreased catalytic efficiencies of their biochemical reactions. Understanding resource allocation is paramount in the study of PAOs and their currently unknown complex metabolic regulation, and metabolic modelling based on biological first principles provides a useful tool to develop a mechanistic understanding.

Bioactive effects of a calcium/sodium phosphosilicate on the resin-dentine interface: a microtensile bond strength, scanning electron microscopy, and confocal microscopy study.

This study evaluated, through microtensile bond strength (µTBS) testing, the bioactive effects of a calcium/sodium phosphosilicate (BAG) at the resin-dentine interface after 6 months of storage in phosphate buffer solution (PBS). Confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) were also performed. Three bonding protocols were evaluated: (i) RES-Ctr (no use of BAG), (ii) BAG containing adhesive (BAG-AD), and (iii) BAG/H (3) PO (4) before adhesive (BAG-PR). The dentin-bonded specimens were prepared for µTBS testing, which was carried out after 24 h or 6 months of storage in PBS. Scanning electron microscopy ultramorphology analysis was performed after debonding. Confocal laser scanning microscopy was used to evaluate the morphological and nanoleakage changes induced by PBS storage. High µTBS values were achieved in all groups after 24 h of storage in PBS. Subsequent to 6 months of storage in PBS the specimens created using the BAG-AD bonding approach still showed no significant reduction in µTBS. Moreover, specimens created using the BAG-AD or the BAG-PR approach showed an evident reduction of nanoleakage after prolonged storage in PBS. The use of BAG-containing adhesive may enhance the durability of the resin-dentine bonds through therapeutic/protective effects associated with mineral deposition within the bonding interface and a possible interference with collagenolytic enzyme activity (matrix metalloproteinases) responsible for the degradation of the hybrid layer.

Influence of air-abrasion executed with polyacrylic acid-Bioglass 45S5 on the bonding performance of a resin-modified glass ionomer cement.

The aim of this study was to test the microtensile bond strength (µTBS), after 6 months of storage in PBS, of a resin-modified glass ionomer cement (RMGIC) bonded to dentine pretreated with Bioglass 45S5 (BAG) using various etching and air-abrasion techniques. The RMGIC (GC Fuji II LC) was applied onto differently treated dentine surfaces followed by light curing for 30 s. The specimens were cut into matchsticks with cross-sectional areas of 0.9 mm(2). The µTBS of the specimens was measured after 24 h or 6 months of storage in PBS and the results were statistically analysed using two-way anova and the Student-Newman-Keuls test (α = 0.05). Further RMCGIC-bonded dentine specimens were used for interfacial characterization, micropermeability, and nanoleakage analyses by confocal microscopy. The RMGIC-dentine interface layer showed no water absorption after 6 months of storage in PBS except for the interdiffusion layer of the silicon carbide (SiC)-abraded/polyacrylic acid (PAA)-etched bonded dentine. The RMGIC applied onto dentine air-abraded with BAG/H(2)O only or with BAG/PAA-fluid followed by etching procedures (10% PAA gel) showed no statistically significant reduction in µTBS after 6 months of storage in PBS. The abrasion procedures performed using BAG in combination with PAA might be a suitable strategy to enhance the bonding durability and the healing ability of RMGIC bonded to dentine.

Therapeutic effects of novel resin bonding systems containing bioactive glasses on mineral-depleted areas within the bonded-dentine interface.

This study aimed in evaluating the effects of two experimental resin bonding systems containing conventional Bioglass 45S5 (BAG) or Zinc-polycarboxylated bioactive glass (BAG-Zn) micro-fillers on the resin-bonded dentine interface after storage in a simulated body fluid solution (SBFS). Three resin bonding systems were formulated: Resin-A: (BAG containing); Resin-B; (BAG-Zn containing); Resin-C (no filler). The ability of the experimental resins to evoke apatite formation was evaluated using confocal Raman spectroscopy. Acid-etched dentine specimens were bonded, and prepared for AFM/nano-indentation analysis in a fully-hydrated status to evaluate the modulus of elasticity (Ei) and hardness (Hi) across the interface at different SBFS storage periods. Further resin-dentine specimens were tested for microtensile bond strength after 24 h or 3 months of SBFS storage. SEM examination was performed after de-bonding and confocal laser microscopy was used to evaluate the ultramorphology of the interfaces and micropermeability. The resin A and B showed a consistent presence of apatite (967 cm(-1)), reduced micropermeability within the resin-dentine interface and a significant increase of the Ei and Hi along the bonded-dentine interface after prolonged SBFS storage. Bond strength values were affected by the resin system (P < 0.0001) and by storage time (P < 0.0001) both after 24 h and 3 months of SBFS storage. In conclusion, resin bonding systems containing bioactive fillers may a have therapeutic effect on the nano-mechanical properties and sealing ability of mineral-depleted resin-dentine interface.

Glass-ionomer and calcium silicate-based cements interactions with human dentine in health and disease: Two-photon fluorescence microscopy and Raman spectroscopy analysis.

OBJECTIVES: To investigate the potential mineralising effects of calcium silicate-based dentine replacement material (Biodentine™) in comparison with glass-ionomer cement (GIC) (Fuji IX™) on different human dentine substrates using a multimodal non-invasive optical assessment. METHODS: Cements were applied on artificially demineralised or naturally carious dentine and stored for 4 weeks in phosphate-rich media +/- tetracycline used for mineralisation labelling. Interfacial dentine was examined from the same sample and location before and after aging using two-photon fluorescence microscopy, fluorescence lifetime imaging (FLIM) and second harmonic generation (SHG) imaging. Additionally, Raman spectroscopy was used to detect changes in the mineral content of dentine. RESULTS: Significant changes in the fluorescence intensity and lifetime were detected in partially demineralised dentine and caries-affected dentine underneath both tested cements, after storage (p < 0.001). This was associated with a significant increase in the mineral content as indicated by the increased intensity of the phosphate Raman peak located at 959 cm-1 (p < 0.0001). Caries-infected dentine showed significant fluorescence changes under Biodentine™ after storage (p < 0.001), but not under GIC (p = 0.44). Tetracycline binding induced a reduction in the fluorescence lifetime with comparable increase in the fluorescence intensity in both cements' groups within the affected dentine (p < 0.001). Significance Two-photon fluorescence microscopy can be used efficiently for non-destructive in-vitro dentine caries characterisation providing a technique for studying the same dentine-cement interface over time and detect changes. Biodentine™ demonstrated comparable remineralising potential to GIC, in addition to inducing remineralisation of caries-infected dentine. This may suggest using Biodentine™ as part of minimally invasive operative dentistry (MID) in caries management.

Methacrylic monomer derived from cardanol incorporated in dental adhesive as a polymerizable collagen crosslinker.

OBJECTIVES: The aim of this study was to evaluate the influence on MMP inhibition, dentin adhesion and physicochemical properties of an adhesive system incorporated with polymerizable collagen crosslinker monomer derived from cardanol. METHODS: The intermediary cardanol epoxy (CNE) was synthesized through cardanol epoxidation, followed by synthesis of cardanol methacrylate through methacrylic acid solvent-free esterification. Zymographic analysis was performed to evaluate the substances' ability to inhibit gelatinolytic enzymes. Collagen crosslinkers were added into adhesives systems according to the following groups: Ybond Universal® (Control), Ybond® + 2 % proanthocyanidin (PAC), Ybond® + 2 % unsaturated cardanol (Cardanol) and Ybond® + 2 % cardanol methacrylate (CNMA). Degree of conversion (DC) of the adhesives was assessed by FT-IR. Disk-shaped specimens were prepared for water sorption (WS) and solubility (SL) tests. Human third molars were sectioned to expose medium dentin and restored according to the different adhesives used (n = 5). Then, the specimens were cut into 1 mm2 sticks to evaluate, after 24 h and 6-month aging, microtensile bond strength (µTBS) and nanoleakage by scanning electron microscopy. Data were analysed with ANOVA and Tukey's post-test (α = 0.05). RESULTS: CNMA and PAC completely inhibited all forms of gelatinolytic enzymes. Cardanol achieved a significantly lowest DC, while the other groups did not differ from each other (p > 0.05). PAC achieved significantly higher water sorption, while CNMA solubility was significantly lower when compared to the other adhesives (p < 0.05). PAC provided a statistically higher 24 h and 6-month aging bond strength. Intermediary similar µTBS were presented by control and CNMA (p = 0.108). All adhesives applied attained significantly reduced bond strength after aging (p < 0.05). Interfaces created using CNMA were almost devoid of silver deposits initially, however all groups showed large amounts of silver deposits on resin-dentin interface subjected to water aging. SIGNIFICANCE: Although CNMA was effective in inhibiting gelatinolytic enzymes, when incorporated into a universal adhesive it could not promote less degradation of the adhesive interface after water aging. Since it is a hydrophobic monomer, CNMA did not interact well with dentin collagen, however it reduced the solubility of the adhesive system besides not interfering in its polymerization.