Poly(4‐vinyl imidazole): A pH‐Responsive Trigger for Hierarchical Self‐Assembly of Multicompartment Micelles Based upon Triblock Terpolymers

Poly(vinyl pyridine) has widely been used as a pH‐responsive polymer to trigger changes in self‐assembly of block copolymer micelles. However, the polymer is known to display toxic features, which limits its ultimate applicability for biological applications. Here, poly(4‐vinyl imidazole) (P4VIm), a much more biocompatible polymer, is used as a pH‐responsive block to modulate the self‐assembly of ABC triblock terpolymers. In this article, the synthesis of the poly(1‐acryloyl fructopyranose)‐block‐ poly(n‐butyl acrylate)‐block‐ poly(4‐vinyl imidazole) (PFruA₅₂‐b‐PBuA₃₀₀‐b‐P4VIm₂₅₀) triblock terpolymers is first discussed by sequential reversible addition fragmentation chain transfer (RAFT) polymerization. Subsequently, the structure formation of the triblock terpolymer is elucidated by step‐wise solvent exchange. The polymer readily dissolves in methanol, but self‐assembles into micelles with PBuA cores and mixed shell in methanol–water mixtures. Solvent exchange against buffer solutions of pH 6–6.5 leads to collapse of P4VIm due to deprotonation and induces self‐assembly into caterpillar‐like non‐spherical nanoparticles, most likely via the formation of intermediate Janus particles. The rearrangement into larger hierarchical structure, as seen by small angle X‐ray scattering (SAXS), is found to process within several hours. The article is concluded by demonstrating lower cytotoxicity values for the present polymer in comparison to a structurally analogous triblock terpolymer based on poly(vinyl pyridine).     

Molecular profiling refines minimal residual disease‐based prognostic assessment in adults with Philadelphia chromosome‐negative B‐cell precursor acute lymphoblastic leukemia

Minimal residual disease (MRD) assessment is an essential tool in contemporary acute lymphoblastic leukemia (ALL) protocols, being used for therapeutic decisions such as hematopoietic stem cell transplantation in high‐risk patients. However, a significant proportion of adult ALL patients with negative MRD still relapse suggesting that other factors (ie, molecular alterations) must be considered in order to identify those patients with high risk of disease progression. We have identified partial IKZF1 gene deletions and CDKN2A/B deletions as markers of disease recurrence and poor survival in a series of uniformly treated adolescent and adult Philadelphia chromosome‐negative B‐cell progenitor ALL patients treated according to the Programa Español de Tratamientos en Hematología protocols. Importantly, CDKN2A/B deletions showed independent significance of MRD at the end of induction, which points out the need for treatment intensification in these patients despite being MRD‐negative after induction therapy.     

Effect of iron on bovine enamel and on the composition of the dental biofilm formed "in situ"

OBJECTIVES: This study investigated in situ the effect of iron (Fe) on the reduction of demineralization of bovine enamel, as well as on the composition of dental biofilm. DESIGN AND METHODS: Twelve volunteers were included in this blind crossover study, which was conducted in two stages of 14 days each. For each stage, the volunteers received palatal appliances containing four blocks of bovine enamel (4 mm x4 mm x 2.5 mm). Six volunteers dripped a solution of 15 mmol L(-1) ferrous sulphate onto the fragments and the remaining six dripped deionized water (eight times per day). After five minutes, a fresh 20% (w/v) sucrose solution was dripped onto all enamel blocks. During the experimental period the volunteers brushed their teeth with non-fluoridated dentifrice. After each stage, the percentage of surface microhardness change (%SMHC) and area of mineral loss (DeltaZ) were determined on enamel and the dental biofilm formed on the blocks was collected and analysed for F, P, Ca, Fe and alkali-soluble carbohydrates. The concentrations of F, Ca and Fe in enamel were also analysed after acid biopsies. RESULTS: There was a statistically significant increase in the P and Fe concentrations in the biofilms treated with ferrous sulphate (p<0.05), which was not observed for F, Ca and alkali-soluble carbohydrates. The group treated with ferrous sulphate had significantly lower %SMHC and DeltaZ when compared to control (p<0.05). CONCLUSIONS: These results showed that ferrous sulphate reduced the demineralization of enamel blocks and altered the ionic composition of the dental biofilm formed in situ.     

Microcomputed and histologic evaluation of calvarial bone grafts: a pilot study in humans

Two evaluation techniques (histology and microcomputed tomography [micro-CT]) were synergistically applied to calvarial bone graft to verify whether additional bone information can be obtained for the assessment of bone grafts. Ten extensive bone defects in the anterior and posterior maxilla or mandible involving crestal bone were treated by grafted blocks and chips of autogenous calvarial bone. The grafts were fixed with lag screws and left to heal for 4 months. No complications were observed. At surgical reentry for implant placement, a cylindric bone biopsy of both graft and native bone was retrieved and analyzed with both micro-CT and standard histology. Two- and three-dimensional (2D, 3D) micro-CT analyses allowed bone connectivity indices to be evaluated. This is useful for estimating bone strength and observing bone structure. The integration of the grafted calvarial bone with the residual bone of the recipient site was considered satisfactory. Histologic analysis allowed observations to be made at a higher resolution. Calvarial bone grafts seem to have positive effects when used as grafting materials. The application of both histologic and micro-CT techniques allows a better evaluation of grafted bone by concurrently allowing 2D and 3D visual and morphometric analysis of bone vitality, structure, turnover, and strength.     

Temporomandibular joint and masticatory muscle involvement in myotonic dystrophy: a study by magnetic resonance imaging

OBJECTIVE: The purpose of this study was to evaluate the masticatory muscles and the temporomandibular joint (TMJ) by magnetic resonance imaging (MRI) in myotonic dystrophy (MD) patients. STUDY DESIGN: MRI of the masticatory muscles and TMJ was performed in 15 MD patients, 11 male and 4 female, aged 16 to 53 years (mean, 31 years). Many of them had dental malocclusion, especially Angle class III and anterior open bite, and 3 complained of recurrent TMJ dislocation. TMJ and masticatory muscle pain was not observed, and joint sounds were noted in only 1 patient. RESULTS: The analysis of MRI scans showed masticatory muscle involvement in 13 patients (86.6%). In 11, the involvement was moderate to intense. The main abnormalities observed were increased intramuscular tissue signal on T1 (fatty infiltration) and volumetric reduction of muscles. Regarding the TMJ, articular disk displacement was seen in only 1 patient, but abnormalities of disk shape were common. Mild bone abnormalities were frequently observed, including changes of shape and contour of bone surface, and sclerosis of bone marrow. In 4 patients the condyle moved anterior to the eminence with the mouth opened fully (condylar hyperexcursion). CONCLUSIONS: This study shows that masticatory muscles are frequently and intensively affected in MD patients. Bone changes are the most consistent abnormalities observed in the TMJ. It is possible that remodeling is caused by biomechanical changes in the jaw as a result of masticatory muscle involvement.     

Polymerization shrinkage and depth of cure of packable composites.

OBJECTIVE: This investigation evaluated polymerization shrinkage and depth of cure of five packable composites. METHOD AND MATERIALS: Five materials were used for the investigation: Alert, Surefil, Solitaire, P60, and Prodigy Condensable. Groups of 10 specimens of each material were made measuring either 2 or 5 mm in thickness, mounted in a testing jig, and polymerized using a dental curing light. Linear shrinkage was recorded and converted to a volumetric value. To evaluate depth of cure, ten specimens of each material were fabricated in both 2- and 5-mm thicknesses, and a Knoop hardness number was recorded on the top and bottom surfaces 5 minutes after light curing. A one-way analysis of variance statistical test was used to determine if there was a significant difference among materials. A Tukey multiple comparison test was then used to determine where significant differences existed. RESULTS: The volumetric shrinkage for the 2-mm-thick specimens from highest shrinkage to lowest were: Solitaire (3.3%), Prodigy Condensable (1.8%), Surefil (1.4%), P60 (1.2%), and Alert (0.2%). The 5-mm-thick specimens were ranked as follows: Solitaire (2.1%), Prodigy Condensable (1.0%), P60 (0.9%), Surefil (0.8%), and Alert (0.3%). Hardness for the bottom surface of the 2-mm-thick specimens showed that P60 (48.5) and Alert (42.6) had the highest values. Solitaire (11.2) had a significantly lower value. Hardness for the bottom surface at 5-mm thickness showed Alert (16.5) and P60 (16.3) with higher values than Surefil (8.9). CONCLUSION: Solitaire had the most shrinkage and Alert the least at both 2- and 5-mm depths. Depth of cure was severely compromised for all materials at 5 mm.     

Mandibular distraction osteogenesis in hemifacial microsomia: Long-term follow-up

AIM: Prospective, longitudinal, clinical long-term follow-up study of a homogeneous sample of children affected by hemifacial microsomia and treated by mandibular distraction osteogenesis. MATERIAL: Eight patients affected by types I and II hemifacial microsomia were operated on at an average age of 5.6 years with an average follow-up of 5.8 years. METHODS: Vertical changes were measured on postero-anterior cephalometric and panoramic radiographs taken sequentially. RESULTS: Angular changes of the infraorbital and nasal floor planes were not significant, showing that distraction osteogenesis starting after 5 years of age did not influence the maxillary skeletal base. Occlusal (plane) cant was reduced by 7 degrees on average following distraction osteogenesis, showing good dentoalveolar plasticity. Mandibular vertical changes showed a gradual return of the asymmetry, with growth in all patients (the ratio between affected and non-affected rami returned by 77% of the correction obtained by means of distraction 5 years postoperatively). CONCLUSION: Although aesthetic and psychological advantages of distraction osteogenesis are well accepted it should only be applied after careful patient selection and honest explanation of the long-term recurrence by genetically determined craniofacial growth patterns.