Determinants of parental seasonal influenza vaccine hesitancy in the Eastern Mediterranean region: A cross-sectional study.

Background: Seasonal influenza vaccine can reduce the risk of influenza-associated hospitalizations and deaths among children. Given that parents are the primary decision makers, this study examined the parental attitude toward childhood influenza vaccine and identified determinants of vaccine hesitancy (VH) in the Eastern Mediterranean region (EMR). Methods: A cross-sectional study was conducted using an anonymous online survey in 14 EMR countries. Parents of children aged 6 months to 18 years were included. The Parent Attitude about Childhood Vaccines (PACV) was used to assess VH. Chi square test and independent t-test were used to test for association of qualitative and quantitative variables, respectively. A structural equations model (SEM) was used to identify direct and indirect determinants of parental VH. Results: Almost half of the parents were hesitant about vaccinating their children against influenza (50.8%). Parental VH was significantly higher among older mothers (37.06 ± 8.8 years, p = 0.006), rural residents (53.6%, p < 0.001), high-income countries residents (50.6%, p < 0.001), and mothers with higher educational levels (52.1%, p < 0.001). Parents of school-aged children (5-9 years) (55.6%, p < 0.001), children free from any comorbidities (52.5%, p < 0.001), children who did not receive routine vaccination at all (51.5%, p = 0.03), children who were not vaccinated against COVID-19 (54.3%, p < 0.001), in addition to parents who were not vaccinated against influenza (57.1%, p < 0.001) were significantly associated with increased likelihood of VH. Parents who were depending on healthcare provider as a source of information regarding vaccines were less likely to report VH (47.9%, p < 0.001), meanwhile those who used social media as their source of health information showed a significantly higher VH (57.2%, p < 0.001). The SEM suggested that mother's age, residence, country income level, child gender, total number of children and source of information regarding vaccines had a direct effect on VH. Meanwhile, parents vaccinated against influenza, children completely or partially vaccinated with routine vaccines and children vaccinated against Coronavirus disease 2019 (COVID-19) had an indirect effect on VH. Conclusion: A high proportion of included parents were hesitant to vaccinate their children against seasonal influenza. This attitude is due to many modifiable and non-modifiable factors that can be targeted to improve vaccination coverage.

Biological properties of lithium-containing surface pre-reacted glass fillers as direct pulp-capping cements.

OBJECTIVE: Surface pre-reacted glass fillers (S-PRG) can release different types of ions and in our previous study, we modified these fillers with lithium chloride (S-PRG/Li-100 mM) to induce reparative dentin formation by activating the Wnt/ß-catenin signaling pathway. Here, we assessed the biological performance of S-PRG/Li-100 mM and compared it with that of mineral trioxide aggregate (MTA) and S-PRG without additives. METHODS: In vivo studies were conducted on male Wistar rats using Masson's trichrome staining in pulp-capped molars. The test materials were implanted subcutaneously to evaluate their capacity for vascularization and biocompatibility. The ability of the test materials to form apatite was tested by immersing them in simulated body fluid. Rhodamine-B staining was conducted to assess their sealing ability in bovine teeth, while their antibacterial activity was evaluated against Streptococcus mutans and Lactobacillus casei in terms of colony-forming units and by live/dead staining. RESULTS: Masson's trichrome staining and tissue-implantation tests confirmed the biocompatibility of S-PRG/Li-100 mM and it was similar to that of MTA and S-PRG; inflammation regression was observed 14 days after operation in the subcutaneous tissues. S-PRG/Li-100 mM promoted the formation of apatite on its surface. Both the S-PRG groups showed higher sealing capability and bactericidal/bacteriostatic activity against oral bacterial biofilms than MTA. SIGNIFICANCE: Lithium-containing surface pre-reacted glass cements exhibit better antibacterial and sealing capabilities than MTA, suggesting their potential as high-performance direct pulp-capping materials.

Performance of a Biodegradable Composite with Hydroxyapatite as a Scaffold in Pulp Tissue Repair.

Vital pulp therapy is an important endodontic treatment. Strategies using growth factors and biological molecules are effective in developing pulp capping materials based on wound healing by the dentin-pulp complex. Our group developed biodegradable viscoelastic polymer materials for tissue-engineered medical devices. The polymer contents help overcome the poor fracture toughness of hydroxyapatite (HAp)-facilitated osteogenic differentiation of pulp cells. However, the composition of this novel polymer remained unclear. This study evaluated a novel polymer composite, P(CL-co-DLLA) and HAp, as a direct pulp capping carrier for biological molecules. The biocompatibility of the novel polymer composite was evaluated by determining the cytotoxicity and proliferation of human dental stem cells in vitro. The novel polymer composite with BMP-2, which reportedly induced tertiary dentin, was tested as a direct pulp capping material in a rat model. Cytotoxicity and proliferation assays revealed that the biocompatibility of the novel polymer composite was similar to that of the control. The novel polymer composite with BMP-2-induced tertiary dentin, similar to hydraulic calcium-silicate cement, in the direct pulp capping model. The BMP-2 composite upregulated wound healing-related gene expression compared to the novel polymer composite alone. Therefore, we suggest that novel polymer composites could be effective carriers for pulp capping.

Surface Pre-Reacted Glass Filler Contributes to Tertiary Dentin Formation through a Mechanism Different Than That of Hydraulic Calcium-Silicate Cement.

The induction of tissue mineralization and the mechanism by which surface pre-reacted glass-ionomer (S-PRG) cement influences pulpal healing remain unclear. We evaluated S-PRG cement-induced tertiary dentin formation in vivo, and its effect on the pulp cell healing process in vitro. Induced tertiary dentin formation was evaluated with micro-computed tomography (µCT) and scanning electron microscopy (SEM). The distribution of elements from the S-PRG cement in pulpal tissue was confirmed by micro-X-ray fluorescence (µXRF). The effects of S-PRG cement on cytotoxicity, proliferation, formation of mineralized nodules, and gene expression in human dental pulp stem cells (hDPSCs) were assessed in vitro. µCT and SEM revealed that S-PRG induced tertiary dentin formation with similar characteristics to that induced by hydraulic calcium-silicate cement (ProRoot mineral trioxide aggregate (MTA)). µXRF showed Sr and Si ion transfer into pulpal tissue from S-PRG cement. Notably, S-PRG cement and MTA showed similar biocompatibility. A co-culture of hDPSCs and S-PRG discs promoted mineralized nodule formation on surrounding cells. Additionally, S-PRG cement regulated the expression of genes related to osteo/dentinogenic differentiation. MTA and S-PRG regulated gene expression in hDPSCs, but the patterns of regulation differed. S-PRG cement upregulated CXCL-12 and TGF-ß1 gene expression. These findings showed that S-PRG and MTA exhibit similar effects on dental pulp through different mechanisms.

Protein S100-A7 Derived from Digested Dentin Is a Critical Molecule for Dentin Pulp Regeneration.

Dentin consists of inorganic hard tissue and organic dentin matrix components (DMCs). Various kinds of bioactive molecules are included in DMCs and some of them can be released after digestion by endogenous matrix metalloproteinases (MMPs) in the caries region. Digested DMCs induced by MMP20 have been reported to promote pulpal wound healing processes, but the released critical molecules responsible for this phenomenon are unclear. Here, we identified protein S100-A7 as a critical molecule for pulpal healing in digested DMCs by comprehensive proteomic approaches and following pulp capping experiments in rat molars. In addition, immunohistochemical results indicated the specific distribution of S100-A7 and receptor for advanced glycation end-products (RAGE) as receptor for S100-A7 in the early stage of the pulpal healing process, and following accumulation of CD146-positive stem cells in wounded pulp. Our findings indicate that protein S100-A7 released from dentin by MMP20 might play a key role in dentin pulp regeneration.

Lithium-containing surface pre-reacted glass fillers enhance hDPSC functions and induce reparative dentin formation in a rat pulp capping model through activation of Wnt/ß-catenin signaling.

Surface pre-reacted glass (S-PRG) fillers are new bioactive molecules used in dental clinic work to fill tooth defects. These fillers release various types of ions (Al+3, BO-3, Na+, SiO3-2, Sr+2 and F-) and exhibit high biocompatibility, antibacterial capability, reduced plaque accumulation, and enhanced osteoblast differentiation. We previously showed that cement of S-PRG fillers could induce tertiary dentin formation in rat models. Previous work also showed that lithium ions can activate the Wnt/ß-catenin signaling pathway in vitro and induce dentin formation in pulpotomized teeth in vivo. In the current study, we sought to enhance the effect of S-PRG cement by incorporating LiCl. We show that treatment of human dental pulp stem cells with eluates from S-PRG/LiCl combination cements leads to an upregulation in cell migration, differentiation, and mineralization in vitro. In pulp-capping animal trials, we found that S-PRG/LiCl cements could induce tertiary dentin formation 28-days post-capping. At 7 days post-capping, we identified both ß-catenin and Axin2 expression using immunofluorescence, indicative of Wnt/ß-catenin signaling activity. In conclusion, S-PRG/LiCl cement is highly effective in promoting human dental pulp stem cells profiles and in enhancing reparative dentin formation in rat teeth through activation of the Wnt/ß-catenin canonical signaling pathway. STATEMENT OF SIGNIFICANCE: This is the first study to assess the behavior of S-PRG fillers containing lithium ions on human dental pulp stem cells. We show that this new combination cement promotes positive cell responses by activating the endogenous Wnt/ß-catenin signaling pathway in the pulp. The Wnt/ß-catenin canonical signaling pathway is involved in many developmental and wound healing processes. The released lithium ions from the S-PRG cement were systematically detected <0.01 mmol/L in our rat model. But it was efficient to induce tertiary dentin formation at the defect site. Since this novel bioactive cement is potentially a promising material for clinical pulp regenerative therapy, future human clinical trials will be needed.

Novel evaluation method of dentin repair by direct pulp capping using high-resolution micro-computed tomography.

OBJECTIVES: We evaluated a novel micro-computed tomography (micro-CT) assessment for quality and quantity of dentin repair, which is difficult to visualize by histological analysis, after direct pulp capping under standardized cavity preparation. MATERIALS AND METHODS: Standardized cavities were prepared on Wistar rats and direct pulp capping was performed using two commercial bioceramics, ProRoot MTA, and iRoot BP Plus. After 2 or 4 weeks, quality and quantity of tertiary dentin formation were evaluated using high-resolution micro-CT analyses including dentin mineral density, dentin mineral contents, compactness and integrity of tertiary dentin, and dentin volume with/without void space. Reproducibility of micro-CT analyses was confirmed by histological evaluation of the same specimen. RESULTS: The exposed pulp area sizes were similar between iRoot BP Plus and ProRoot MTA. Micro-CT analysis of 2-week samples showing compactness of tertiary dentin was significantly higher in iRoot BP Plus than ProRoot MTA (p < 0.05). Tertiary dentin volume without void space, dentin mineral contents, and density were not significantly different between the groups. In 4-week samples, a significant increase was observed in dentin mineral density, compactness, and dentin volume with/without void space induced by iRoot BP Plus (p < 0.05). Micro-CT analysis of tertiary dentin integrity demonstrated that some ProRoot MTA specimens had small defects and lacked continuity (6/512 images). No defects were observed with iRoot BP Plus. CONCLUSIONS: Micro-CT analysis was confirmed as an accurate, objective, and inclusive approach for evaluating quality and quantity of dentin repair. CLINICAL RELEVANCE: These multifaceted approaches to evaluate pulp capping materials may accelerate review processes, ultimately improving vital pulp therapy.