[The Roles of Aß in Alzheimer's Disease: In Light of the Latest Findings].

The 'amyloid hypothesis', initially put forward in 1992, posits that amyloid ß protein (Aß) contributes to neurodegeneration through aberrant aggregation. In the process of this aberrant aggregation, Aß forms oligomers, protofibrils, and mature fibrils, ultimately developing plaques. These mature fibrils and plaques were believed to be the culprits behind the neurotoxicity and neurodegeneration seen in Alzheimer's disease (AD). However, growing evidence in recent years has led to the 'Aß oligomer hypothesis', which suggests that the intermediate forms of aggregates, such as oligomers and protofibrils, exhibit stronger neurotoxicity than the mature forms. Consequently, efforts have been made to develop anti-Aß antibody drugs that specifically target these intermediate aggregates. Such interventions hold promise as disease-modifying treatments for AD.

Advanced statistical analyses to reduce inconsistencies in bond strength data focused on donor factors: A six-factor analysis using linear mixed and nonlinear regression models.

PURPOSE: This study aimed to investigate the effects of the age and sex of tooth donors on dentin bond strength. METHODS: A total of 38 extracted teeth (12 male and 26 female donors; age range: 17-82 years) were used in this study. In addition to donor age and sex, four other microtensile bond strength (µTBS) test specimen factors were evaluated: dentin position, bonding area, presence of voids at the interface, and computed tomography (CT) values of dentin. The µTBS was measured immediately (24 h) and 6 months after storage in water. After the µTBS testing, linear mixed and nonlinear regression models were used to analyze the effects of these factors on the µTBS data. RESULTS: The results from the linear mixed model revealed that the bonding area (P = 0.02), presence of voids at the interface (P = 0.04), and storage time (P < 0.001) significantly affected bond strength. In contrast, no correlation was observed between the µ TBS and dentin position (P = 0.08) or sex (P = 0.07). The results of the nonlinear regression model with robust variance-covariance estimators revealed that age significantly affected bond strength (P < 0.001). In addition, a significant positive correlation was found between µTBS and age (P < 0.001), with nonlinearity (P = 0.002). However, no correlation was observed between the µTBS and CT values (P = 0.69) without nonlinearity (P = 0.39). CONCLUSIONS: These findings suggest that bond strength increases with age until 60 years but not afterward.

Effect of Silver Diamine Fluoride on Bonding Performance and Ultra-morphological Characteristics to Sound Dentin.

OBJECTIVES: This study aimed to evaluate microtensile bond strength (µTBS) and ultra-morphological characteristic changes in sound dentin resulting from silver diamine fluoride (SDF) when using adhesives. METHODS: Ninety-six extracted human third molars were divided into the SDF-contaminated dentin group and the sound dentin group. In the SDF-contaminated dentin group, 38% SDF was agitated for 1 min, left undisturbed for 2 min, and rinsed with distilled water for 30 s. Then, each group was further subdivided into six subgroups (n = 8 / group) according to application modes: self-etch mode (SE) and etch-and-rinse mode (ER) followed by three adhesives: (1) Scothbond Universal Plus Adhesive (SUP); (2) G2-Bond Universal Adhesive (G2B); and (3) Clearfil Mega Bond 2 (MB2). All specimens were restored with resin composite and were stored in distilled water for 24 h before µTBS testing. Data from the µTBS test were analyzed using Three-way ANOVA and Duncan test (p < 0.05). The morphology of fractured surface and adhesive-dentin interfaces were evaluated by SEM, TEM, and STEM. Further elemental analysis was done by EDX. RESULTS: All SDF-contaminated dentin groups demonstrated significantly lower µTBS than sound dentin groups. All ER groups had higher µTBS than SE groups, except for G2B in the sound dentin group. STEM/EDX revealed an SDF-dentin-reacted layer in the SDF-contaminated dentin group. SIGNIFICANCE: SDF had an adverse effect on adhesives. Additionally, ER mode is preferable when bonded to SDF-contaminated dentin. A calcium and fluoride-contained layer was observed in all SDF-contaminated dentin.

Lack of in vivo mutagenicity of carbendazim in the liver and glandular stomach of MutaMice.

BACKGROUND: Carbendazim (methyl 2-benzimidazolecarbamate, CASRN: 10605-21-7) exhibits spindle poisoning effects and is widely used as a fungicide. With respect to genotoxicity, carbendazim is deemed to be non-mutagenic in vitro, but it causes indicative DNA damage in vivo and chromosome aberrations in vitro and in vivo. In this study, we examined the mutagenicity of carbendazim in vivo. RESULTS: MutaMice were treated with carbendazim orally at doses of 0 (corn oil), 250, 500, and 1,000 mg/kg/day once a day for 28 days. A lacZ assay was used to determine the mutant frequency (MF) in the liver and glandular stomach of mice. MutaMice were administered up to the maximum dose recommended by the Organization for Economic Co-operation and Development Test Guidelines for Chemicals No. 488 (OECD TG488). The lacZ MFs in the liver and glandular stomach of carbendazim-treated animals were not significantly different from those in the negative control animals. In contrast, positive control animals exhibited a significant increase in MFs in both the liver and glandular stomach. CONCLUSIONS: Carbendazim is non-mutagenic in the liver and glandular stomach of MutaMice following oral treatment.

Effect of filler contents on the bond strength of CAD/CAM resin crowns: New resin primer versus conventional silane agents.

Purpose This study aims to evaluate the effects of resin primers containing methyl methacrylate (MMA) and silane agent on the bonding effectiveness of indirect resin composite blocks with three different filler contents.Methods A commercially available computer-aided design/computer-aided manufacturing (CAD/CAM) resin composite block and two experimental resin composite blocks with different filler contents were alumina-blasted and two surface treatments (primer and silane agent) were applied. The resin cement was built up, and the micro-tensile bond strength (µTBS) was measured after 24 hours, 1 month or 3 months of water storage (n = 24 per group). The fracture surfaces after µTBS measurements and resin block/cement interface were observed by scanning electron microscopy (SEM).Results The primer treatment group showed a significantly higher bond strength than the silane group only in F0 (filler content 0 wt%) group (P < 0.001). In the primer group, F0 and F41 (filler content 41 wt%) groups showed significantly higher bond strengths than F82 (filler content 82 wt%) group (P < 0.001). In contrast, in the silane group, F41 group showed significantly higher bond strength than F0 and F82 groups (P < 0.001), and F82 group showed significantly higher bond strength than F0 group (P < 0.001). SEM revealed that the matrix resin was partially destroyed on the fracture surface of the primer group, and an uneven interface surface was observed compared with that of the silane group.Conclusions MMA-containing primers showed higher bonding effectiveness to CAD/CAM resin composite blocks than the silane treatment.

In vivo mutagenicity assessment of orally treated tert-butyl hydroperoxide in the liver and glandular stomach of MutaMouse.

BACKGROUND: tert-Butyl hydroperoxide (TBHP; CAS 75-91-2), a hydroperoxide, is mainly used as a polymerization initiator to produce polyethylene, polyvinyl chloride, and unsaturated polyester. It is a high-production chemical, widely used in industrial countries, including Japan. TBHP is also used as an additive for the manufacturing of food utensils, containers, and packaging (UCP). Therefore, there could be consumer exposure through oral intake of TBHP eluted from UCPs. TBHP was investigated in various in vitro and in vivo genotoxicity assays. In Ames tests, some positive results were reported with and/or without metabolic activation. As for the mouse lymphoma assay, the positive result was reported, regardless of the presence or absence of metabolic activation enzymes. The results of some chromosomal aberrations test and comet assay in vitro also demonstrated the genotoxic positive results. On the other hand, in in vivo tests, there are negative results in the bone marrow micronucleus test of TBHP-administered mice by single intravenous injection and the bone marrow chromosomal aberration test using rats exposed to TBHP for 5 days by inhalation. Also, about dominant lethal tests, the genotoxic positive results appeared. In contrast, there is little information about in vivo mutagenicity and no information about carcinogenicity by oral exposure. RESULTS: We conducted in vivo gene mutation assay using MutaMice according to the OECD Guidelines for the Testing of Chemicals No. 488 to investigate in vivo mutagenicity of TBHP through oral exposure. After repeated dosing for 28 days, there were no significant differences in the mutant frequencies (MFs) of the liver and glandular stomach up to 300 mg/kg/day (close to the maximum tolerable dose (MTD)). The positive and negative controls produced the expected responses. CONCLUSIONS: These findings show that orally administrated TBHP is not mutagenic in the mouse liver and glandular stomach under these experimental conditions.

Effect of sodium hypochlorite on bonding performance of universal adhesives to pulp chamber dentin.

Abstract Background/purpose: The most widely utilized irrigation solution in endodontic therapy is sodium hypochlorite (NaOCl). The purpose of this study was to assess the effects of NaOCl on the bond strength of four universal adhesives and one two-step self-etch adhesive to pulp chamber dentin. Materials and methods: One hundred sixteen extracted sound human third molars were used in this study. All the teeth were divided into two groups: (1) with NaOCl treatment and (2) without NaOCl treatment. These two groups were subdivided into five bonding groups: G-Premio Bond (GP), Beautibond Xtreme (BBX), Scotchbond Universal (SBU), Clearfil Universal Bond Quick (UBQ), and Clearfil Megabond 2 (MB2). The microtensile bond strength (µTBS), the fracture mode analysis, resin-dentin interface and dentin surface were observed by SEM. Two-way ANOVA was performed to analyze the µTBS (α = 0.05). Results: The µTBS of the NaOCl group significantly decreased for GP and MB2 (P < 0.05). Significant effects of adhesive (F = 12.182, P < 0.001), and irrigation (F = 27.224, P < 0.001) on the µTBS were observed, whereas interaction between adhesive and irrigation was not significant (F = 1.761, P = 0.144). The adhesive layer with variable thickness was observed in all groups with different morphological structures. Conclusion: The effect of NaOCl treatment on the µTBS differs depending on the type of adhesives.

Derivation of subacute guidance values for chemical contaminants of drinking water quality standard in Japan.

The concentration of chemicals in drinking water may transiently and accidently exceed the Drinking Water Quality Standard (DWQS). If the level of a contaminant is not expected to cause adverse effects for a limited period of exposure, immediate suspension of the water supply may not be necessary. Assessments should be conducted using subacute guidance values (SGVs). In this study, we assessed 26 chemicals for the DWQS to establish the SGVs. Principally, a key study was selected from subacute studies to derive a Subacute Reference Dose (saRfD). The SGV was calculated from the saRfD for adults (drinking water intakes: 40 mL/kg/day) and children (drinking water intakes: 150 mL/kg/day). No allocation factor was applied to derive the SGV. We established the SGV for 20 chemicals, which were 2-38 times higher than the corresponding DWQS. However, SGVs for six chemicals were the same as the corresponding DWQS. Therefore, immediate action will be required for these six accidental contaminants. Our established SGVs are useful for assessing accidental contamination.

In vivo mutagenicity assessment of styrene in MutaMouse liver and lung.

BACKGROUND: Styrene (CAS 100-42-5) is widely used as polystyrene and acrylonitrile-butadiene-styrene resin such as plastic, rubber, and paint. One of the primary uses of styrene is food utensils and containers, but a small amount of styrene transferred into food can be ingested by eating. Styrene is metabolized into styrene 7,8-oxide (SO). SO is mutagenic in bacteria and mouse lymphoma assays. It is clastogenic in cultured mammalian cells. However, styrene and SO are not clastogenic/aneugenic in rodents, and no rodent in vivo gene mutation studies were identified. METHODS: To investigate the mutagenicity of orally administered styrene, we used the transgenic rodent gene mutation assay to perform an in vivo mutagenicity test (OECD TG488). The transgenic MutaMouse was given styrene orally at doses of 0 (corn oil; negative control), 75, 150, and 300 mg/kg/day for 28 days, and mutant frequencies (MFs) were determined using the lacZ assay in the liver and lung (five male mice/group). RESULTS: There were no significant differences in the MFs of the liver and lung up to 300 mg/kg/day (close to maximum tolerable dose (MTD)), when one animal with extremely high MFs that were attributed to an incidental clonal mutation was omitted. Positive and negative controls produced the expected results. CONCLUSIONS: These findings show that styrene is not mutagenic in the liver and lung of MutaMouse under this experimental condition.

Formation and evaluation of mechanism-based chemical categories for regulatory read-across assessment of repeated-dose toxicity: A case of hemolytic anemia.

The aim of this study is to define chemical categories that can be applied to regulatory read-across assessments for repeated-dose toxicity, by classifying toxic substances based on their structures and mechanism of actions (MoAs). Hemolytic anemia, which often appears primarily, was examined as an example. An integrated database was constructed by collecting publicly available datasets on repeated-dose toxicity, in which 423 out of a total of 1518 chemicals were identified as capable of inducing hemolytic anemia. Subsequently, by grouping these chemicals based on their chemical structures and plausible MoAs on hemolytic substances, we identified the following categories: (i) anilines, (ii) nitrobenzenes, (iii) nitroanilines, (iv) dinitroanilines, (v) ethylene glycol alkyl ethers, (vi) hydroquinones, (vii) oximes, and (viii) hydrazines. In these categories, the toxicant and the measurable key events leading to hematotoxicity were identified, thereby allowing us to justify the categories and to discriminate the category substances. Moreover, toxicokinetics seems to critically affect the hemolytic levels of the category substances. Overall, the categories were validated through a comprehensive analysis of the collected information, while the utility was demonstrated by conducting a case study on the selected category. Further endeavors with this approach would attain categories for other organ toxicity endpoints.

Effect of tooth temperature on the dentin bonding durability of a self-curing adhesives: The discrepancy between the laboratory setting and inside the mouth.

A two-bottle self-curing universal adhesive (Tokuyama Universal Bond; Tokuyama Dental) that does not require a long waiting time or light curing after application of the bonding material has been developed. This study aimed to evaluate the influence of tooth and adhesive temperature during the bonding procedure on the effectiveness of dentin bonding. The results showed that the tooth temperature affected the effectiveness of the dentin bonding; therefore, to determine the precise bonding ability in the laboratory, the temperature of the tooth must be raised until it is the same as that of the oral cavity. In addition, the temperature of the material did not affect bonding effectiveness; this result confirms that it does not matter whether the refrigerated product is used soon after its removal from the refrigerator or after it reaches room temperature in the clinic.

Prevalence of common aneuploidy in twin pregnancies.

The incidence of chromosomal abnormalities in twin pregnancies is not well-studied. In this retrospective study, we investigated the frequency of chromosomal abnormalities in twin pregnancies and compared the incidence of chromosomal abnormalities in dichorionic diamniotic (DD) and monochorionic diamniotic (MD) twins. We used data from 57 clinical facilities across Japan. Twin pregnancies of more than 12 weeks of gestation managed between January 2016 and December 2018 were included in the study. A total of 2899 and 1908 cases of DD and MD twins, respectively, were reported, and the incidence of chromosomal abnormalities in one or both fetuses was 0.9% (25/2899) and 0.2% (4/1908) in each group (p = 0.004). In this study, the most common chromosomal abnormality was trisomy 21 (51.7% [15/29]), followed by trisomy 18 (13.8% [4/29]) and trisomy 13 (6.9% [2/29]). The incidence of trisomy 21 in MD twins was lower than that in DD twins (0.05% vs. 0.5%, p = 0.007). Trisomy 21 was less common in MD twins, even when compared with the expected incidence in singletons (0.05% vs. 0.3%, RR 0.15 [95% CI 0.04-0.68]). The risk of chromosomal abnormality decreases in twin pregnancies, especially in MD twins.

Development of dental inspection method: Nondestructive evaluation of an adhesive interface by ACTIVE acoustic emission.

PURPOSE: This study aims to confirm the usefulness of active acoustic emission (Active AE) for reproducible and non-invasive generation of physical external force which is required for conventional AE. METHODS: Experiment 1: A root dentin-resin adhesive interface was observed. The post space was filled with a dual-cure resin composite core material with and without adhesive. The vibration characteristics of the data obtained from the time-frequency analysis were evaluated. Experiment 2: A crown-abutment tooth adhesive interface was observed. Adhesive resin cement was used for luting the crown and adhesion states in the same specimen over time were analyzed with three measurements: at trial-fitting, immediately after luting, and 2 weeks after luting. Data were subjected to time-frequency analysis and relationships between amplitude (indicating loudness) and frequency (indicating the sound component) were analyzed. RESULTS: Experiment 1: Time-frequency analysis confirmed multiple peak frequencies for each specimen without adhesive and monomodal peak frequency in all specimens using adhesive. Experiment 2: Two weeks after luting, all specimens showed a single major peak except one which showed multiple weak peaks. The three-dimensional visualization of time-frequency analysis revealed one specimen with multiple weak peaks while all others displayed a single, low-amplitude band at 2 weeks after luting. CONCLUSION: The state of the adhesive interface can be evaluated using active AE. This basic technique may prove useful to evaluate changes in the adhesive interface of prostheses over time.

Does the bonding effectiveness of a fiber post/resin composite benefit from mechanical or chemical treatment? Seven methods for saliva-contaminated surfaces.

PURPOSE: This study examined four cleaning methods and three chemical treatments for artificial saliva-contaminated fiber posts in terms of bonding durability to resin composite core materials. METHODS: Non-contaminated fiber posts (Tokuyama FR Post, Tokuyama Dental) and those contaminated (GC Fiber Post, GC) with artificial saliva (Saliveht Aerosol, Teijin Pharma) were used. Washing and drying (WD), alcohol cleaning (AlC), H3PO4 etching (P/WD), alumina blasting (B/D) for decontamination and silanization (Clearfil Ceramic Primer Plus, Kuraray Noritake Dental, Si), resin priming (HC Primer, Shofu, MMA), and bonding resin application (Clearfil Universal Bond Quick, Kuraray Noritake Dental, BR) for chemical treatment were performed. The treated fiber post was planted inside a cylindrical tube and filled with resin composite (DC Core Automix ONE, Kuraray Noritake Dental). The specimen was sectioned, and a push-out test was performed after 24 h, 1 month, and 3 months. The fracture surface was observed using a scanning electron microscope (SEM). RESULTS: Adhesion between the non-contaminated fiber post and resin composite did not improve by silanization and decreased by alumina blasting. SEM observations revealed a fractured glass fiber by alumina blasting. Saliva contamination decreased the bond strength between the fiber post and resin composite; however, recovery was achieved by WD, Alc, P/WD, and B/D. Compared to Si, BR (P = 0.009) was effective in restraining the long-term durability of bonding, whereas MMA (P = 0.99) was not. CONCLUSION: The application of bonding resin after alcohol cleaning is the most convenient and effective clinical procedure for fiber post surface treatment.

Four-year clinical evaluation of CAD/CAM indirect resin composite premolar crowns using 3D digital data: Discovering the causes of debonding.

PURPOSE: To analyze the causes of debonding of computer-aided design/computer-aided manufacturing (CAD/CAM) indirect resin composite premolar crowns with a focus on the morphological factors of the crown and abutment teeth. METHODS: The clinical courses of 109 CAD/CAM indirect resin composite crowns were observed, and the patients' background characteristics, crown locations, luting methods, types of abutments, distal-most/non-distal-most molars, and types of resin blocks were confirmed. To investigate the influence of the morphology of the crown and abutment teeth, the 1) vertical dimension of the abutment teeth, 2) taper, and 3) thickness of the crown occlusal surface during events were measured from the three-dimensional digital data. The Kaplan-Meier method and multivariable Cox proportional hazard model were used for the statistical analyses. The nonlinearity of the effect of each comparison factor was included in the model. RESULTS: Complications included 21 debonding cases, two crown fractures, five root fractures, and two core debondings. The cumulative no-debonding and no-crown-fracture rate over 1423 days (3 years and 11 months) was 77.4%. The multivariable Cox regression analysis revealed that the abutment teeth type of tooth (first or second premolar) (P = 0.02) and luting materials (P < 0.01) significantly influenced the debonding frequency. All morphological factors (1-3) significantly influenced the debonding. The hazard ratios and nonlinear graph indicated that the crown thickness was less effective than the vertical dimension and taper. CONCLUSION: The combination analysis of clinical outcomes and 3D digital data revealed that preparation of the abutment is important for avoiding crown debonding.

Combination of a silane coupling agent and resin primer reinforces bonding effectiveness to a CAD/CAM indirect resin composite block.

The effects of silanization and resin primer application on CAD/CAM indirect resin composite block bonding were investigated. KATANA AVENCIA P blocks (Kuraray Noritake Dental) were treated with a silane coupling agent and/or a resin primer. The contact angles (CAs) of resin primer were observed before and after silanization. Panavia V5 (Kuraray Noritake Dental) was built after each treatment. Bond strengths were measured, and the interface was analyzed by energy dispersive X-ray spectroscopy (EDS). The CA showed that silane treatment improved the wettability of the resin primer to the resin block. The combination treatment of the silane and resin primer showed significantly higher bond strength than no treatment, only in the silanization or resin primer group (p<0.001 each). EDS analysis showed that the resin primer penetrated both cement and block sides. The combination of the silane and resin primer improved bonding effectiveness between the resin block and resin cement.

Status of decontamination methods after using dentin adhesion inhibitors on indirect restorations: An integrative review of 19 publications.

The purpose of this review was to assess the literature regarding the decontamination of resin cement before the luting procedure in order to provide clinicians with a comparative overview of decontamination effects. A total of 19 articles were selected for inclusion in this review. The results indicated that bonding effectiveness is reduced due to residual adhesion inhibitors such as saliva, blood, hemostatic agents, and temporary/provisional cement. Self-etching and self-adhesive systems tend to be more negatively affected by adhesion inhibitors than do etch and rinse systems. Cleaning with an ultrasonic scaler or rotating brush have demonstrated conflicting effects in several studies. Some studies have reported that phosphoric acid has negative effects and recommend mild acid for decontamination. The application of phosphoric acid followed by sodium hypochlorite has been shown to help avoid negative effects. Alumina blasting has been investigated as a mechanical cleaning method in a relatively large number of experiments, most of which have confirmed its effectiveness. An intraoral cleaner containing functional monomers that has become commercially available in recent years is a promising method in clinical practice because it can easily and effectively remove temporary adhesive material. In addition, adhesion inhibitors can be easily removed from resin-coated dentin surfaces.

Do resin core build-ups obtain the benefits of higher bonding ability from direct or indirect technique?

Purpose This study evaluated the effects of different materials (composite resin system including a photo-cure adhesive (DC) vs. resin cement system including a self-etching primer (PV)) and techniques (direct vs. indirect) for resin core build-up on the bonding performance to root canal dentin.Methods The human teeth were decoronated and root canal preparation was performed. All specimens were randomly divided into four groups according to the combinations of the methods (Direct or Indirect) and the materials (DC: Clearfil DC Core, Kuraray Noritake Dental or PV: Panavia V5, Kuraray Noritake Dental). Micro-tensile bond strength (µTBS) and push-out tests were performed. Scanning electron microscope observations of the interface were also performed, and microcomputed tomography and optical coherence tomography were applied to evaluate the sealing ability.Results The Indirect group had significantly higher µTBSs than the Direct group in the DC group (P = 0.0076). The PV group had significantly higher bond strengths than the DC group in both the Direct and Indirect groups (P < 0.001). The Direct/PV group demonstrated significantly higher push-out bond strength than the Direct/DC group (P < 0.001). In the Direct/PV group, the formation of resin tags was observed even on the apical side of the canal. Microleakage was more clearly observed in the DC group than in the PV group.Conclusions PV has a higher bonding ability to root canal dentin than DC. When using DC, the indirect technique exhibited a higher bonding ability than the direct technique.

Development of dental inspection method: nondestructive evaluation of a dentin-adhesive interface by acoustic emission.

Purpose The state of adhesion between root dentin and a resin composite core material was inspected using acoustic emission (AE).Methods A total of 14 human incisors and premolars were used to prepare "no-adhesive group" and "adhesive group" specimens. For "adhesive group" specimens, a bonding agent was applied to root canal dentin. The entire post space was subsequently filled with a resin composite for both specimen groups. The prepared specimens were fixed onto a jig on which an AE sensor was installed. A zirconia ball was used for the impact test, and a vibration wave generated by the collision was measured by the system using an AE sensor. The obtained data were subjected to time-frequency analysis using analysis software (LabVIEW), and the relationship between the amplitude indicating the loudness and the frequency indicating the sound component was analyzed.Results Zirconia-ball collision tests using AE revealed differences between the groups with respect to the waveform of vibration waves transmitted to the root dentin through the root dentin-resin interface. The time-frequency analysis of the obtained data confirmed that multiple peaks were observed for each specimen in the no-adhesive group, whereas a single characteristic vibration peak was observed for all specimens in the adhesive group.Conclusions The state of the adhesive interface was successfully evaluated by AE. This demonstration is expected to lead to the development of a device that can detect problems at the bonding interface between the prostheses and tooth substances.