Development of Amorphous Solid Dispersion Sustained-Release Formulations with Polymer Composite Matrix-Regulated Stable Release Plateaus.

PURPOSE: This study was designed to develop ibuprofen (IBU) sustained-release amorphous solid dispersion (ASD) using polymer composites matrix with drug release plateaus for stable release and to further reveal intrinsic links between polymer' matrix ratios and drug release behaviors. METHODS: Hydrophilic polymers and hydrophobic polymers were combined to form different composite matrices in developing IBU ASD formulations by hot melt extrusion technique. The intrinsic links between the mixed polymer matrix ratio and drug dissolution behaviors was deeply clarified from the dissolution curves of hydrophilic polymers and swelling curves of composite matrices, and intermolecular forces among the components in ASDs. RESULTS: IBU + ammonio methacrylate copolymer type B (RSPO) + poly(1-vinylpyrrolidone-co-vinyl acetate) (PVP VA64) physical mixtures presented unstable release behaviors with large error bars due to inhomogeneities at the micrometer level. However, IBU-RSPO-PVP VA64 ASDs showed a "dissolution plateau phenomenon", i.e., release behaviors of IBU in ASDs were unaffected by polymer ratios when PVP VA64 content was 35% ~ 50%, which could reduce risks of variations in release behaviors due to fluctuations in prescriptions/processes. The release of IBU in ASDs was simultaneously regulated by the PVP VA64-mediated "dissolution" and RSPO-PVP VA64 assembly-mediated "swelling". Radial distribution function suggested that similar intermolecular forces between RSPO and PVP VA64 were key mechanisms for the "dissolution plateau phenomenon" in ASDs at 35% ~ 50% of PVP VA64. CONCLUSIONS: This study provided ideas for developing ASD sustained-release formulations with stable release plateau modulated by polymer combinations, taking full advantages of simple process/prescription, ease of scale-up and favorable release behavior of ASD formulations.

The combined effects of polystyrene of different sizes and cadmium in mouse kidney tissues.

Environmental accumulation of nano- and microplastics pose serious risks to human health. Polystyrene (PS) is a polymer commonly used in the production of plastics. However, PS can adsorb cadmium (Cd), thereby influencing bioavailability and toxicity in vivo. Moreover, PS and Cd can accumulate in the mammalian kidney. Therefore, the aim of the present study was to assess the effects of combined exposure to PS and Cd in the kidney. Kidney damage was evaluated in male mice gavaged with PS (diameter, 100 nm and/or 1 µm) and Cd for 25 days.The results showed that PS at 100 nm caused more severe oxidative damage and cell apoptosis than PS at 1 µm. Combined exposure to PS at both 100 nm and 1 µm caused more severe kidney damage than the single administration groups. The extent of kidney toxicity caused by Cd differed with the combination of PS particles at 100 nm vs. 1 µm. The degree of damage to kidney function, pathological changes, and cell apoptosis induced by Cd+100 nm PS+1µm PS was the most severe. An increase in the Bax/Bcl2 ratio and overexpression of p53 and caspase-3 revealed that renal cell apoptosis might be induced via the mitochondrial pathway. Collectively, these findings demonstrate that the size of PS particles dictates the combined effects of PS and Cd in kidney tissues. Kidney damage caused by the combination of different sizes of PS particle and Cd is more complicated under actual environmental conditions.

Impacts of microplastic type on the fate of antibiotic resistance genes and horizontal gene transfer mechanism during anaerobic digestion.

Microplastics (MPs) and antibiotic resistance genes (ARGs) are important pollutants in waste activated sludge (WAS), but their interactions during anaerobic digestion (AD) still need to be further explored. This study investigated variations in ARGs, mobile genetic elements (MGEs), and host bacteria during AD under the pressure of polyamide (PA), polyethylene (PE), and polypropylene (PP). The results showed that the MPs increased methane production by 11.7-35.5%, and decreased ARG abundance by 5.6-24.6%. Correlation analysis showed that the decrease of MGEs (plasmid, prophage, etc.) promoted the decrease of the abundance of multidrug, aminoglycoside and tetracycline resistance genes. Metagenomic annotation revealed that the reduction of key host bacteria (Arenimonas, Lautropia, etc.) reduced the abundance of major ARGs (rsmA, rpoB2, etc.). Moreover, PP MPs contributed to a reduction in the abundance of functional genes related to the production of reactive oxygen species, ATP synthesis, and cell membrane permeability, which was conducive to reducing the potential for horizontal gene transfer of ARGs. These findings provide insights into the treatment of organic waste containing MPs.

Micro-computed tomography analysis of calcium hydroxide delivery efficacy in C-shaped canal system of mandibular second molars.

BACKGROUND: Calcium hydroxide [Ca(OH)2] is widely accepted as a biocompatible interappointment intracanal medicament. This study aimed to analyze the efficacy of Ca(OH)2 placement into the C-shaped canal system of mandibular second molars using the syringe method with and without lentulo spiral utilizing micro-computed tomography (micro-CT). METHODS: Twenty-four extracted mandibular second molars were instrumented and classified into C-shaped floors (n = 12) and non-C-shaped floors (n = 12). Both groups were placed with Ca(OH)2 using the syringe system, then all teeth were scanned and cleaned, and placed with Ca(OH)2 again but with the syringe system followed by lentulo spiral and rescanned. The specimens were scanned using micro-CT to analyze the volume, volume percentage, uncontacted surface area, and uncontacted surface area percentage of Ca(OH)2 with the two delivery methods in the entire canal and at the apical 4 mm of the canal. Mann-Whitney test and Wilcoxon signed-rank test were used to determine the statistical differences among the groups. RESULTS: Syringe administration used in conjunction with lentulo spiral presented lower uncontacted surface area, a lower percentage of uncontacted surface area, larger volume, and a higher percentage of volume than syringe without lentulo spiral (P < 0.05). There was no significant difference between the C-shaped floor group and the non-C-shaped floor group (P > 0.05) in the Ca(OH)2 uncontacted surface area, volume, and percentages at different regions of canals and among different delivery techniques groups. CONCLUSIONS: The lentulo spiral and syringe technique combination can increase the volume and contacted surface area of Ca(OH)2 in the C-shaped canal system of mandibular second molars.

Biomimetic liposomal nanozymes improve breast cancer chemotherapy with enhanced penetration and alleviated hypoxia.

BACKGROUND: Doxorubicin (Dox) has been recommended in clinical guidelines for the standard-of-care treatment of breast cancer. However, Dox therapy faces challenges such as hypoxia, acidosis, H2O2-rich conditions and condensed extracellular matrix in TME as well as low targeted ability. METHODS: We developed a nanosystem H-MnO2-Dox-Col NPs based on mesoporous manganese dioxide (H-MnO2) in which Dox was loaded in the core and collagenase (Col) was wrapped in the surface. Further the H-MnO2-Dox-Col NPs were covered by a fusion membrane (MP) of inflammation-targeted RAW264.7 cell membrane and pH-sensitive liposomes to form biomimetic MP@H-MnO2-Dox-Col for in vitro and in vivo study. RESULTS: Our results shows that MP@H-MnO2-Dox-Col can increase the Dox effect with low cardiotoxicity based on multi-functions of effective penetration in tumor tissue, alleviating hypoxia in TME, pH sensitive drug release as well as targeted delivery of Dox. CONCLUSIONS: This multifunctional biomimetic nanodelivery system exhibited antitumor efficacy in vivo and in vitro, thus having potential for the treatment of breast cancer.

An application framework of 3D assessment image registration accuracy and untouched surface area in canal instrumentation laboratory research with micro-computed tomography.

OBJECTIVES: The purpose of this study was to develop a customized framework for evaluating the registration accuracy of four registration techniques and measuring the untouched surface area of canal instrumentation by visually inspecting and calculating the overlapping area of the surfaces. METHODS: Twenty-one mandibular incisors were scanned by micro-computed tomography before and after instrumentation. Elastix registration, surface registration, manual registration, and DataViewer registration techniques were used to align the pre- and post-operative datasets. The customized MeVisLab framework was created to investigate the registration accuracy by visual inspection and calculating overlapping areas. The canal surfaces were imported into the same framework to measure the untouched surface area and the consistence test was validated. The correlation between registration accuracy and untouched surface area was analyzed. RESULTS: There is a statistically significant difference between manual registration and automatic registration (P < 0.05). There is no statistical difference between the two untouched surface measure methods (P > 0.05). The partial correlation coefficients for the untouched surface area and registration accuracy were 0.45 (P < 0.05). CONCLUSIONS: This application framework based on free customizable software, allows a new method to measure registration accuracy and untouched surface area in an efficient and sensitive way. The application of a precise registration method would improve the quality of micro-CT canal instrumentation studies. CLINICAL RELEVANCE: This study developed a customized framework based on free software for evaluating the registration accuracy of different registration techniques and measuring the untouched surface area of canal instrumentation could help researchers to improve the quality of micro-CT studies of canal instrumentation.

The Feasibility of Electromagnetic Navigation Technique to Achieve Preoperative Plan in Mandibular Angle Osteotomy.

BACKGROUND: In contrast to the most commonly used optical navigation system, electromagnetic navigation has huge potential in operations with a narrow field. The purpose of this experiment was to test and confirm whether the electromagnetic navigation method the authors developed for mandibular angle osteotomy (MAO) met clinical requirements. METHODS: Using a dental splint that could be repeatedly mounted on teeth, registration between surgical plan and actual field was performed automatically. RESULTS: Navigation of MAO was first performed on 10 mandibular models. The position precision measured using a coordinate measuring machine was 1.30±0.61 mm. Then, a navigation experiment was performed on 4 patients. Accuracy in actual operation measured by the NDI pointing sensor was 1.89±0.76 mm. Our noninvasive automatic registration process reduced the surgical exposure time and eliminated the bias of the manual selection of registration points. CONCLUSIONS: This preliminary study confirmed the feasibility of the electromagnetic navigation technique in terms of both applicability and accuracy in MAO surgery.

Antimicrobial effects of agitational irrigation on single- and multispecies biofilms in dentin canals.

This study aimed to compare the antibacterial effects of different agitation devices on single- and multispecies biofilms in dentin canals using confocal laser scanning microscopy (CLSM). Dentin blocks were prepared from human root dentin. Enterococcus faecalis and multiple species were introduced into the dentinal tubules via centrifugation and incubation. Two infected dentin samples were placed at 8 and 16 mm in a customized model. Samples were randomly divided into eight groups according to the agitation device used: syringe needle irrigation, EndoActivator, passive ultrasonic irrigation (PUI), and EDDY, at 2.5% or 6% NaOCl concentrations. The samples were stained and observed using CLSM. Statistical analysis was performed using an independent sample t test and analysis of variance. Linear models were used to assess the joint impact of the experimental groups on the proportion of biofilms killed. No significant differences were observed between the killing rates of the single- and multispecies biofilms. Both concentrations of NaOCl significantly increased the percentage of dead bacteria compared with the control. Biofilms in dentin tubules was more effectively killed when NaOCl was agitated; however, the difference between PUI and EDDY was not significant. Significantly more bacteria were killed in dentin blocks placed at 8 mm than at 16 mm (p < 0.05). In conclusion, EDDY was as effective as PUI when combined with NaOCl. However, the apical portion, which had a low antimicrobial efficiency, remains a concern. Mechanical instrumentation is incapable of completely eradicating bacteria, and additional research is required to improve the efficacy of root canal disinfection.

Creating and analyzing digital scans of a mandibulectomy cast with simulated trismus.

STATEMENT OF PROBLEM: Trismus associated with maxillofacial defects resulting from tumor resection or radiotherapy can make dental treatment uncomfortable for patients. Using an intraoral scanner instead of making a conventional impression could help to make prosthetic rehabilitation more comfortable. However, limited information is available regarding the feasibility and accuracy of intraoral scanners for scanning mandibular defects. PURPOSE: The purpose of this in vitro study was to evaluate the feasibility and accuracy of using an intraoral scanner to digitize a cast of a mandibular defect under various simulated trismus conditions. MATERIAL AND METHODS: An intraoral scanner was used to scan the mandibular cast under different simulated degrees of trismus (mouth opening 10, 20, and 30 mm) and nontrismus (mouth opening 40 mm). The surface areas captured were compared. The datasets were loaded into a 3-dimensional (3D) evaluation software program and then superimposed for precision analysis and on reference data for trueness analysis. One-way analysis of variance was used to compare surface area captured, precision, and trueness of the measurement under the different mouth opening conditions (α=.05). RESULTS: The surface area for which 3D data were obtained by the intraoral scanner ranged from 3199.1 to 6161.6 mm2. The area differed significantly under all mouth opening conditions (P=.001), with a smaller scanned surface area captured in severe trismus (10 mm). Precision ranged from 0.032 to 0.056 mm, and trueness from 0.037 to 0.076 mm. No significant differences were seen in precision (P=.312), but significant differences were seen in trueness (P=.016) under all trismus conditions. CONCLUSIONS: Using an intraoral scanner appears feasible for digitizing mandibular defect casts with simulated mild and moderate trismus. The accuracy of the obtained data was clinically acceptable.

Microcomputed tomography analysis of the radicular residual dentin thickness in mandibular second molars after virtual fiber post placement: Identification of danger zones.

STATEMENT OF PROBLEM: Mandibular second molars have variable root, pulp chamber floor, and radicular groove morphologies, potentially affecting residual dentin thickness and post placement suitability. However, an identification of the danger zones is lacking. PURPOSE: The purpose of this in vitro study was to investigate the residual dentin thickness in the danger zone of mandibular second molars after virtual fiber post placement by using a simulation method based on microcomputed tomography (µCT). MATERIAL AND METHODS: A total of 84 extracted mandibular second molars were scanned using µCT and classified according to root morphology (separate or fused) and pulp chamber floor morphologies (C-shaped, non-C-shaped, or no pulp chamber floor). Fused-root mandibular second molars were further classified based on the radicular groove type (V-, U-, or Ω-shaped). All specimens were accessed, instrumented, and rescanned with µCT. Two types of commercial fiber posts were also scanned. Clinical fiber post placement was simulated in all prepared canals by using a multifunctional software program. The minimum residual dentin thickness of each root canal was measured and analyzed by using nonparametric tests to identify the danger zone. Perforation rates were calculated and recorded. RESULTS: Larger fiber posts decreased minimum residual dentin thickness (P<.05) and increased perforation rate. In regard to mandibular second molars with separate roots, the distal root canal exhibited a significantly higher minimum residual dentin thickness than the mesiobuccal and mesiolingual root canals (P<.05). However, no significant difference in minimum residual dentin thickness was found between the different canals in fused-root mandibular second molars with C-shaped pulp chamber floors (P<.05). Fused-root mandibular second molars with Ω-shaped radicular grooves had a lower minimum residual dentin thickness than those with V-shaped radicular grooves (P<.05) and demonstrated the highest perforation rate. CONCLUSIONS: The morphologies of the root, pulp chamber floor, and radicular groove were correlated with residual dentin thickness distribution in mandibular second molars after fiber post placement. A comprehensive understanding of mandibular second molar morphology is essential for determining the suitability of post-and-core crown restorations after endodontic treatment.

Liposome-Mediated In Situ Formation of Type-I Heterojunction for Amplified Photoelectrochemical Immunoassay.

Exploiting innovative sensing mechanisms and their rational implementation for selective and sensitive detection has recently become one of the mainstream research directions of photoelectrochemical (PEC) bioanalysis. In contrast to existing conventional strategies, this study presents a new liposome-mediated method via in situ combining ZnInS nanosheets (ZIS NSs) with SnS2 to form a ZIS NSs/SnS2 type-I heterojunction on fluorine-doped tin oxide (FTO) electrodes for highly sensitive PEC immunoassays. Specifically, alkaline phosphatase (ALP)-encapsulated liposomes were confined within 96-well plates by sandwich immunorecognition and subsequently subjected to lysis treatment. Enzymatically produced H2S by the released ALP was then directed to react with Sn(IV) to engender the ZIS NSs/SnS2 type-I heterojunction on the FTO/ZIS NSs-Sn(IV) electrode, resulting in a change in the photogenerated electron-hole transfer path of the photoelectrode and reduction in current signaling. Exemplified by heart-type fatty acid binding protein (h-FABP) as a target, the constructed PEC sensor showed good stability and selectivity in a biosensing system. Under optimal conditions, the as-prepared sensing platform displayed high sensitivity for h-FABP with a dynamic linear response range of 0.1-1000 pg/mL and a lower detection limit of 55 fg/mL. This research presents the liposome-mediated PEC immunoassay based on in situ type-I heterojunction establishment, providing a new protocol for analyzing various targets of interest.

Activity-Based Protein Profiling Probe for the Detection of Enzymes Catalyzing Polysorbate Degradation.

Polysorbates are nonionic surfactants that have been widely used in biotherapeutic formulations to prevent protein aggregation and denaturation. However, polysorbates are subject to degradation after prolonged storage if certain lipases are present in the biotherapeutic product. Because the degradation of polysorbates compromises the shelf life of biotherapeutics and leads to the formation of undesirable products such as protein aggregates and subvisible particles, it is important to identify the active enzymes that catalyze polysorbate hydrolysis. In this study, we developed a novel fluorophosphonate activity-based protein profiling (ABPP) probe (termed the REGN probe), which mimics the structure of polysorbate and targets lipases catalyzing polysorbate degradation. We demonstrated that the REGN probe could enrich certain lipases from Chinese hamster ovary (CHO) cell lysate by more than 100-fold compared with direct tryptic digestion. Furthermore, we found that the REGN probe had higher lipase enrichment efficiency than commercially available ABPP probes including fluorophosphonate-biotin (FP-biotin) and FP-desthiobiotin. Remarkably, the REGN probe can enrich several lipases that cannot be labeled by commercial probes, such as lysosomal acid lipase and cytosolic phospholipase A2. Additionally, we showed that lipases with abundances as low as 0.08 ppm in drug substances were detected by the REGN probe enrichment and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Collectively, we have developed a novel ABPP probe with higher enrichment efficiency and broader coverage for lipases compared with commercial probes, and this probe can be used to detect the trace level of lipases in biotherapeutic products and to facilitate their development and manufacturing.

Characterization of microplastics in indoor and ambient air in northern New Jersey.

Airborne microplastics (MPs) could have negative impacts on human health and pollute water, soil, and sediment. This study explored the distributions, compositions, and morphology of airborne microplastics in the indoor and ambient air in New Jersey, United States. Microplastic fibers, films, and fragments of Polystyrene (PS), Polyethylene terephthalate (PET), Polyethyelene (PE), Polyvinyl chloride (PVC) and Polypropylene (PP) were identified in office, hallway, classroom, and single-family house in this study. The deposition rates of synthetic fibers with length from 35 µm to 1000 µm were highest in the single-family house ((1.96 ± 1.09) × 104 fibers/m2/day) and lowest in the classroom ((6.20 ± 0.57) × 103 fibers/m2/day), suggesting that residential houses are a major source of microplastic fibers. However, for film-like plastics with surface areas ranging from 200 µm2 to 5000 µm2, a high deposition rate of (8.13 ± 2.17) × 103 films/m2/day was observed in the classroom, whereas the lowest deposition rate of (4.45 ± 0.27) × 103 films/m2/day was found in the hallway, probably because plastic films such as PE are intensively used in the classroom environments. The deposition rate of microplastics in the ambient air acquired on a building roof was only about 2-8% of the indoor deposition rates. The microplastics with similar textures but different sizes were identified in both total atmospheric deposition and particulate samples (PM2.5 and PM10), suggesting degradation from microplastics to nanoplastics. The main microplastics found in indoor air samples were PE fragments or fibers, different from those in the outdoor ambient air that were dominated by PVC fragments. These results unravel the properties of airborne microplastics in urban environments that are important to understanding their fate, transport, and potential health risks.

Long-term efficacy of GPi DBS for craniofacial dystonia: a retrospective report of 13 cases.

This study evaluated the long-term efficacy of globus pallidus internus (GPi) deep brain stimulation (DBS) in the treatment of craniofacial dystonia (Meige syndrome) and investigated the correlation between the volume of tissue activated (VTA) in the GPi and each subregion and movement score improvement. We retrospectively analyzed the clinical data of 13 patients with drug-refractory Meige syndrome who were treated with GPi DBS. The pre- and postoperative Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores were compared. The relationships between the preoperative baseline variables and improvement in the BFMDRS-Movement (BFMDRS-M) score were analyzed. LEAD-DBS software was used for the three-dimensional reconstruction of the GPi and implanted electrodes. The correlations between the GPi-VTA and score improvement were analyzed. The average follow-up period was 36.6 ± 11.0 months (18-55 months). At 3 months after the stimulation and the final follow-up visit, the improvements in the BFMDRS-M score were 58.2 and 54.6%, and the improvements in the BFMDRS-Disability (BFMDRS-D) score were 53.6 and 51.7%, respectively. At the final follow-up visit, the improvements in the BFMDRS-M scores of the eye, mouth, and speech/swallowing were significant (P < 0.001). Age was an independent predictor of improvement in the BFMDRS-M score after DBS (P = 0.005). A decrease in the BFMDRS-M score was significantly positively correlated with the GPi-VTA (r = 0.757, P = 0.003). GPi DBS is an effective method for treating drug-refractory Meige syndrome. LEAD-DBS software can be used as an effective aid for visualization programming after DBS.

Micro-computed tomography analysis of root canal morphology and thickness of crown and root of mandibular incisors in Chinese population.

OBJECTIVES: The aim of this study was to investigate the root canal morphology and the thickness of crown and root of mandibular incisors in a Chinese subpopulation by micro-computed tomography (micro-CT). METHODS: In total, 208 mandibular incisors were scanned using micro-CT. The anatomical features of the canals (canal configuration, apical constriction, foramen-to-apex distance, accessory canal vertical distribution, and canal geometrical parameters) and the thickness of the crown and root 2/3 were evaluated. RESULTS: Three canal categories, labeled as Single (77.88%), Merged (15.87%), and Separated (6.25%), were summarized. The most frequent constriction type in main foramina was single constriction (42.53%). Wide and narrow diameters in a single main foramen were 0.37 ± 0.14 mm and 0.26 ± 0.07 mm, respectively. The distance from the anatomical foramen to the physiological foramen and the anatomical apex was 0.49 ± 0.20 mm and 0.36 ± 0.28 mm, respectively. During the virtual root-end resection, 97.12% of roots underwent successful resection at the 2-mm level, with the foramina visible on the resection surface. During 2-D cross-sectional analyses, the shape parameters of the root and canal showed significant positive correlation (P < 0.05). The thickest and thinnest walls were the incisal and proximal walls (P < 0.05) of the crown, respectively. The buccal walls were significantly thicker than the lingual walls on the crown (P < 0.05), whereas the lingual walls were thicker on the root 2/3 (P < 0.05). CONCLUSIONS: This study provides detailed information about the root canal morphology and thickness of the crown and root of mandibular incisors in a Chinese population. An understanding of morphology can benefit endodontic treatment. CLINICAL RELEVANCE: Adequate knowledge of the crown, root, and canal morphology, as well as the thickness distribution of the crown and root, is essential for successful root canal therapy and prevention of complications.

Phosphorylated PAMAM dendrimers: an analog of dentin non-collagenous proteins, enhancing the osteo/odontogenic differentiation of dental pulp stem cells.

OBJECTIVES: Polyamidoamine (PAMAM) dendrimers have well-defined structures, with monodispersity and easily modified surface groups, and they have broad applications in biomedicine. In this study, phosphorylated PAMAM (P-PAMAM) dendrimers were synthesized based on the idea of mimicking the phosphorylated proteins of dentin non-collagenous proteins (DNCP). Then, proliferation and osteo/odontogenic differentiation effects of P-PAMAM on dental pulp stem cells (DPSCs) were investigated and were compared with DNCP. MATERIALS AND METHODS: P-PAMAM was synthesized via the Mannich-type reaction. DNCP were extracted directly from human dentin with ethylenediaminetetraacetic acid (EDTA) solution. Then, the conditioned medium of P-PAMAM and DNCP were prepared respectively and applied to DPSCs. Proliferation of P-PAMAM was investigated with CCK-8, flow cytometry, and EdU test. Osteo/odontogenic differentiation of P-PAMAM was analyzed using alkaline phosphatase activity and staining, RT-PCR, western blot, alizarin red staining, and immunofluorescence staining. RESULTS: Fourier transform infrared spectroscopy and 1H nuclear magnetic resonance revealed that PAMAM were successfully phosphorylated. Western blot verified that the extracted DNCP contained dentin-related proteins DSPP, OPN, and BMP2. In cell proliferation, there was no apparent difference between P-PAMAM, DNCP, and Control groups (P > 0.05). P-PAMAM and DNCP upregulated related genes and proteins expression (DSPP/DSPP, COL-1/COL-1, ALP/ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN) and matrix mineralization. Still, the potential was lower than that of DNCP (P < 0.05). CONCLUSIONS: P-PAMAM dendrimers, as a biomimetic analog of DNCP, promote osteo/odontogenic differentiation of DPSCs without influencing their proliferation at a low concentration. CLINICAL RELEVANCE: This preliminary study about P-PAMAM dendrimers is expected to provide a more convenient bioactive macromolecular material for the regeneration of the pulp-dentin complex.

Dentin remineralization in acidic solution without initial calcium phosphate ions via poly(amido amine) and calcium phosphate nanocomposites after fluid challenges.

OBJECTIVES: A previous study showed that the combination of poly(amido amine) (PAMAM) and rechargeable composites with nanoparticles of amorphous calcium phosphate (NACP) induced dentin remineralization in an acidic solution with no initial calcium (Ca) and phosphate (P) ions, mimicking the oral condition of individuals with dry mouths. However, the frequent fluid challenge in the oral cavity may decrease the remineralization capacity. Therefore, the objective of the present study was to investigate the remineralization efficacy on dentin in an acid solution via PAMAM + NACP after fluid challenges for the first time. METHODS: The NACP nanocomposite was stored in a pH 4 solution for 77 days to exhaust its Ca and P ions and then recharged. Demineralized dentin samples were divided into four groups: (1) control dentin, (2) dentin coated with PAMAM, (3) dentin with recharged NACP composite, and (4) dentin with PAMAM + recharged NACP. PAMAM-coated dentin was shaken in phosphate-buffered saline for 77 days to desorb PAMAM from dentin. Samples were treated in pH 4 lactic acid with no initial Ca and P ions for 42 days. RESULTS: After 77 days of fluid challenge, PAMAM failed to prevent dentin demineralization in lactic acid. The recharged NACP nanocomposite raised the pH to above 6.5 and re-released more than 6.0 and 4.0 mmol/L Ca and P ions daily, respectively, which inhibited further demineralization. In contrast, the PAMAM + NACP combined method induced great dentin remineralization and restored the dentin microhardness to 0.54 ± 0.04 GPa, which approached that of sound dentin (P = 0.426, P > 0.05). CONCLUSIONS: The PAMAM + NACP combination achieved dentin remineralization in an acid solution with no initial Ca and P ions, even after severe fluid challenges. CLINICAL RELEVANCE: The novel PAMAM + NACP has a strong and sustained remineralization capability to inhibit secondary caries, even for individuals with dry mouths.

Assessment of Robot-Assisted Mandibular Contouring Surgery in Comparison With Traditional Surgery: A Prospective, Single-Center, Randomized Controlled Trial.

BACKGROUND: Few clinical studies on robot-assisted surgery (RAS) for mandibular contouring have been reported. OBJECTIVES: The aim of this study was to follow the long-term effectiveness and safety of RAS for craniofacial bone surgery. METHODS: This small-sample, early-phase, prospective, randomized controlled study included patients diagnosed with mandibular deformity requiring mandibular contouring surgery. Patients of both genders aged 18 to 30 years without complicated craniofacial repair defects were enrolled and randomly assigned in a 1:1 ratio by a permuted-block randomized assignments list generated by the study statistician. The primary outcomes were the positioning accuracy and accuracy of the osteotomy plane angle 1 week after surgery. Surgical auxiliary measurement index, patient satisfaction scale, surgical pain scale, perioperative period, and complications at 1 week, 1 month, and 6 months after surgery were also analyzed. RESULTS: One patient was lost to follow-up, resulting in a total of 14 patients in the traditional surgery group and 15 in the robot-assisted group (mean [standard deviation] age, 22.65 [3.60] years). Among the primary outcomes, there was a significant difference in the positioning accuracy (2.91 mm vs 1.65 mm; P < 0.01) and angle accuracy (13.26º vs 4.85º; P < 0.01) between the 2 groups. Secondary outcomes did not significantly differ. CONCLUSIONS: Compared to traditional surgery, robot-assisted mandibular contouring surgery showed improved precision in bone shaving, as well as higher safety.

Shaping outcome of ProTaper NEXT for root canal preparation in mandibular incisors: a micro-CT study.

BACKGROUND: Relatively high incidence of single canals with oval or round shape were observed in human mandibular incisors. In order to investigate the influence of the root canal morphology on root canal preparation, the shaping outcome of ProTaper NEXT in oval and round canals of mandibular incisors were evaluated by using micro-computed tomography (micro-CT) analysis. METHODS: This experiment was approved by the School Medical Ethics Committee. The sample size calculation was conducted using G*Power software. Intact mandibular incisors with a single canal were selected. Oval canals (2 < aspect ratio (AR) ≤ 4) and round canals (AR ≤ 2) were pair-matched according to canal length, and assigned to two experimental groups (13 per group). ProTaper NEXT was used for root canal preparation for both groups. Untouched canal wall (UCW), root canal morphological parameters and three-dimensional (3D) dentin thickness were evaluated in the entire root canal and each canal third after micro-CT scanning. STATISTICAL ANALYSIS: Data were collected and analyzed with Mann-Whitney test and Friedman test using SPSS statistics software 25 (P < 0.05). Additionally, correlations of UCW area with canal morphological parameters were also investigated. RESULTS: After root canal preparation, no significant difference was observed in all analyzed parameters in the apical third between oval and round canal groups (P > 0.05). In the coronal two thirds of the canal, the post-operative structure model index (SMI), form factor and roundness were significantly increased, while the AR was significantly decreased in both groups (P < 0.05). In addition, in the coronal two thirds, significantly more UCW and higher UCWΔ% was observed in oval canal group (P < 0.05). Furthermore, UCW correlated very strongly to canal major diameter (0.924) and initial volume (0.938), and strongly to canal form factor (- 0.724), minor diameter (0.799) and canal area (0.882). Proximal dentin wall was associated with significantly thinner pre-operative dentin thickness and higher amount of dentin removal after root canal preparation in both oval and round canal groups. CONCLUSIONS: (1) Both types of canals were more conical after root canal preparation, but oval root canals tend to leave more UCW area than round canals in the coronal two thirds of mandibular incisors, which contributes to the challenge for endodontic infection control. (2) Root canal preparation usually results in excessive dentin removal in the proximal dentin wall comparing with buccal and lingual walls in both types of canals of mandibular incisors.

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OBJECTIVES: To investigate the influencing factors for the quality of bowel preparation before colonoscopy in children and the association of the interval from the last administration of laxative to the start of colonoscopy (shortly referred to as waiting time) with the quality of bowel preparation. METHODS: A retrospective analysis was performed for the children who were admitted to the Department of Gastroenterology, Children's Hospital of Nanjing Medical University, from January to November 2020, and received bowel preparation with polyethylene glycol electrolyte powder combined with diet control before colonoscopy. According to the score of Boston bowel preparation scale, they were divided into two groups: adequate bowel preparation group (n=337) and inadequate bowel preparation group (n=30). Related data were collected from the children in both groups, including general information, possible influencing factors for the quality of bowel preparation, adverse reactions associated with bowel preparation, duration of colonoscopy, and postoperative diagnosis. Univariate and multivariate analyses were used to explore the influencing factors for the quality of bowel preparation. RESULTS: The univariate analysis showed that age, body weight, and waiting time were associated with inadequate bowel preparation (P<0.05). The multivariate analysis showed that older age (OR=2.155, 95%CI: 1.087-4.273, P=0.028) and longer waiting time (OR=1.559, 95% CI: 1.191-2.041, P=0.001) were independent risk factors for inadequate bowel preparation. The receiver operating characteristic (ROC) curve analysis showed that the cut-off value of waiting time was 5.5 hours in determining whether bowel preparation was adequate or not, with a sensitivity of 90.0%, a specificity of 50.7%, and an area under the ROC curve of 0.708. After grouping based on waiting time, it was found that the incidence rate of inadequate bowel preparation in the ≥5.5 hours group was significantly higher than that in the <5.5 hours group [14.0% (27/193) vs 1.7% (3/174), P<0.001]. CONCLUSIONS: For children who use polyethylene glycol electrolyte powder combined with diet control for bowel preparation, older age is an independent risk factor for inadequate bowel preparation before colonoscopy, which may be associated with an insufficient dose of polyethylene glycol in older children. Longer waiting time is also an independent risk factor for inadequate bowel preparation, and it is recommended that the waiting time should not exceed 5.5 hours.