Pyk2 deficiency enhances bone mass during midpalatal suture expansion

OBJECTIVE: To determine if Pyk2 deficiency increases midpalatal suture bone mass and preserves sutural integrity after maxillary expansion. SETTING AND SAMPLE: Thirty-six male Pyk2 knockout (KO) and control (WT) mice at 6 weeks of age. MATERIALS AND METHODS: Mice received nickel-titanium spring expanders delivering 0 g (no intervention control), 10 or 20 g force for 14 days. High-resolution micro-CT was used to determine bone volume/tissue volume (BV/TV), sutural width and intermolar width. Effects on osteoclasts, chondrocytes and suture morphology were determined by histomorphometry. RESULTS: Pyk2-KO controls (0 g) had 7% higher BV/TV compared with WT controls. Expanded Pyk2-KO maxillae also exhibited 12% (10 g) and 18% (20 g) higher BV/TV than WT mice. Although bone loss following expansion occurred in both genotypes, BV/TV was decreased to a greater extent in WT maxillae (-10% at 10g; -22% at 20 g) compared with Pyk2-KO maxillae (-11% only at 20 g). Expanded WT maxillae also showed a greater increase in sutural width, intermolar width and fibrous connective tissue width compared with expanded Pyk2-KO maxillae. Moreover, osteoclast number was increased 77% (10 g) and 132% (20 g) in expanded WT maxillae, but remained unchanged in expanded Pyk2-KO, compared to their respective controls. Cartilage area and chondrocyte number were increased to the same extent in expanded WT and Pyk2-KO sutures. CONCLUSIONS: These findings suggest that midpalatal suture expansion increases osteoclast formation in WT but not Pyk2-KO mice, leading to higher BV/TV in expanded Pyk2-KO maxillae. These studies suggest Pyk2-targeted strategies may be beneficial to increase bone density and preserve sutural integrity during maxillary expansion

Precision of the virtual occlusal record

Objectives: To evaluate the precision of the virtual occlusal record using the Carestream CS3600 Intraoral Scanner (Carestream Dental, Atlanta, Ga). Materials and methods: A total of 20 participants were recruited for this prospective study using preestablished inclusion/exclusion criteria. A complete intraoral scan and two bite registrations were obtained. The participants were instructed to bite with normal pressure when bite registrations were acquired. Contact locations, size (circumference), and intensity were identified on the maxillary first molars and canines. Agreement between contact size and intensity was assessed with intraclass correlation coefficients. Kappa statistics evaluated agreement in contact locations. Statistical significance was set at P < .05. Results: All participant data were included for statistical analysis. Between the two bite registrations, nonstatistically significant differences were observed in the proportion of locations with contacts (P = .7681). A nonstatistically significant difference (-0.25 mm, P = .8416) in mean contact circumference size was observed. A statistically significant difference in mean contact intensity was observed (P = .0448). When evaluating agreement between the bite registrations, a weak correlation for size (intraclass correlation coefficient = 0.35) and intensity (intraclass correlation coefficient = 0.32) was observed as well as a moderate agreement for contact location (κ coefficient = 0.67). Conclusions: The findings suggest that the Carestream intraoral scanner software possesses adequate precision when acquiring the location and size of the contacts in bite registrations. The scanner failed to demonstrate adequate precision when acquiring contact intensities in bite registrations. Additional research is warranted to further investigate the precision of virtual occlusal records with currently available software systems

Tumor-Targeted Delivery of IL-2 by NKG2D Leads to Accumulation of Antigen-Specific CD8+ T Cells in the Tumor Loci and Enhanced Anti-Tumor Effects

Interleukin-2 (IL-2) has been shown to promote tumor-specific T-cell proliferation and differentiation but systemic administration of IL-2 results in significant toxicity. Therefore, a strategy that can specifically deliver IL-2 to the tumor location may alleviate concerns of toxicity. Because NKG2D ligands have been shown to be highly expressed in many cancer cells but not in healthy cells, we reason that a chimeric protein consisting of NKG2D linked to IL-2 will lead to the specific targeting of IL-2 to the tumor location. Therefore, we created chimeric proteins consisting of NKG2D linked to Gaussia luciferase (GLuc; a marker protein) or IL-2 to form NKG2D-Fc-GLuc and NKG2D-Fc-IL2, respectively. We demonstrated that NKG2D linked to GLuc was able to deliver GLuc to the tumor location in vivo. Furthermore, we showed that TC-1 tumor-bearing mice intramuscularly injected with DNA encoding NKG2D-Fc-IL2, followed by electroporation, exhibited an increased number of luciferase-expressing E7-specific CD8+ T cells at the tumor location. More importantly, treatment with the DNA construct encoding NKG2D-Fc-IL2 significantly enhanced the therapeutic anti-tumor effects generated by intradermal vaccination with therapeutic HPV DNA in tumor-bearing mice. Therefore, by linking NKG2D to IL2, we are able to specifically deliver IL-2 to the tumor location, enhancing antigen-specific T-cell immune response and controlling tumor growth. Our approach represents a platform technology to specifically deliver proteins of interest to tumor loci

Characterization of a Drosophila Alzheimer's Disease Model: Pharmacological Rescue of Cognitive Defects

Transgenic models of Alzheimer's disease (AD) have made significant contributions to our understanding of AD pathogenesis, and are useful tools in the development of potential therapeutics. The fruit fly, Drosophila melanogaster, provides a genetically tractable, powerful system to study the biochemical, genetic, environmental, and behavioral aspects of complex human diseases, including AD. In an effort to model AD, we over-expressed human APP and BACE genes in the Drosophila central nervous system. Biochemical, neuroanatomical, and behavioral analyses indicate that these flies exhibit aspects of clinical AD neuropathology and symptomology. These include the generation of Aβ40 and Aβ42, the presence of amyloid aggregates, dramatic neuroanatomical changes, defects in motor reflex behavior, and defects in memory. In addition, these flies exhibit external morphological abnormalities. Treatment with a γ-secretase inhibitor suppressed these phenotypes. Further, all of these phenotypes are present within the first few days of adult fly life. Taken together these data demonstrate that this transgenic AD model can serve as a powerful tool for the identification of AD therapeutic interventions

Orthodontic movement of a maxillary central incisor with a horizontal root fracture treated using an intra-radicular fibre splint

This paper reports the case of a 15-year-old boy with a horizontal root fracture in the left maxillary central incisor along with class II division 1 malocclusion for whom a fixed orthodontic treatment was planned. The fracture was present at the junction of apical and middle-third as a result of trauma 2 years back. No splinting was carried out at that time and the tooth was found to be vital, asymptomatic and showed a type-1 repair pattern. An intentional root canal treatment was carried out for placement of an intra-radicular fiber splint, nearly 3 mm beyond the fracture line. Orthodontic treatment was initiated after a month; to which the fractured and splinted tooth responded successfully. This report highlights the successful use of an intra-radicular splint for horizontally fractured tooth requiring orthodontic treatment