Miles to go (mtgo) encodes FNDC3 proteins that interact with the chaperonin subunit CCT3 and are required for NMJ branching and growth in Drosophila.

Analysis of mutants that affect formation and function of the Drosophila larval neuromuscular junction (NMJ) has provided valuable insight into genes required for neuronal branching and synaptic growth. We report that NMJ development in Drosophila requires both the Drosophila ortholog of FNDC3 genes; CG42389 (herein referred to as miles to go; mtgo), and CCT3, which encodes a chaperonin complex subunit. Loss of mtgo function causes late pupal lethality with most animals unable to escape the pupal case, while rare escapers exhibit an ataxic gait and reduced lifespan. NMJs in mtgo mutant larvae have dramatically reduced branching and growth and fewer synaptic boutons compared with control animals. Mutant larvae show normal locomotion but display an abnormal self-righting response and chemosensory deficits that suggest additional functions of mtgo within the nervous system. The pharate lethality in mtgo mutants can be rescued by both low-level pan- and neuronal-, but not muscle-specific expression of a mtgo transgene, supporting a neuronal-intrinsic requirement for mtgo in NMJ development. Mtgo encodes three similar proteins whose domain structure is most closely related to the vertebrate intracellular cytosolic membrane-anchored fibronectin type-III domain-containing protein 3 (FNDC3) protein family. Mtgo physically and genetically interacts with Drosophila CCT3, which encodes a subunit of the TRiC/CCT chaperonin complex required for maturation of actin, tubulin and other substrates. Drosophila larvae heterozygous for a mutation in CCT3 that reduces binding between CCT3 and MTGO also show abnormal NMJ development similar to that observed in mtgo null mutants. Hence, the intracellular FNDC3-ortholog MTGO and CCT3 can form a macromolecular complex, and are both required for NMJ development in Drosophila.

A potent and selective Sirtuin 1 inhibitor alleviates pathology in multiple animal and cell models of Huntington's disease.

Protein acetylation, which is central to transcriptional control as well as other cellular processes, is disrupted in Huntington's disease (HD). Treatments that restore global acetylation levels, such as inhibiting histone deacetylases (HDACs), are effective in suppressing HD pathology in model organisms. However, agents that selectively target the disease-relevant HDACs have not been available. SirT1 (Sir2 in Drosophila melanogaster) deacetylates histones and other proteins including transcription factors. Genetically reducing, but not eliminating, Sir2 has been shown to suppress HD pathology in model organisms. To date, small molecule inhibitors of sirtuins have exhibited low potency and unattractive pharmacological and biopharmaceutical properties. Here, we show that highly selective pharmacological inhibition of Drosophila Sir2 and mammalian SirT1 using the novel inhibitor selisistat (selisistat; 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide) can suppress HD pathology caused by mutant huntingtin exon 1 fragments in Drosophila, mammalian cells and mice. We have validated Sir2 as the in vivo target of selisistat by showing that genetic elimination of Sir2 eradicates the effect of this inhibitor in Drosophila. The specificity of selisistat is shown by its effect on recombinant sirtuins in mammalian cells. Reduction of HD pathology by selisistat in Drosophila, mammalian cells and mouse models of HD suggests that this inhibitor has potential as an effective therapeutic treatment for human disease and may also serve as a tool to better understand the downstream pathways of SirT1/Sir2 that may be critical for HD.

Management of root-fractured incisors in a 12-year-old followed with implant treatment 7 years after traumatic injury: a case report.

Trauma to the maxillary anterior teeth is a frequent occurrence in children and adolescents. Coronal fractures may now be successfully treated by reattachment of the fractured portions with the latest enamel and dentin bonding agents. Root fractures present with more challenging problems. Conservative and proper management of root fractures will greatly help the preservation of the alveolar bone to facilitate subsequent implant placement. This is a case report of such management spanning over many years, from adolescence to adulthood, when the implants were placed for the final esthetic ceramic crowns.

Use of onplants as stable anchorage for facemask treatment: a case report.

A hexagonal onplant of 7.7 mm diameter was placed on the palatal bone of the maxilla in an 1-year five-month-old female patient with a Class III malocclusion and midface deficiency. Elastic traction (400 g per side) was applied from a facemask to the onplant at 30 degrees to the occlusal plane 12 hours per day for 12 months. The maxilla was found to have displaced forward and downward by 2.9 mm. The mandible was rotated downward and backward. There was a 3 degrees increase in mandibular plane angle and an increase in the lower face height. Clinically, there was a significant improvement in midface esthetics, noted by an increase in fullness of the infraorbital region and correction of the skeletal discrepancy between the maxillary and mandibular jaw relationship. Contrary to the reports that use teeth rather than onplants as anchorage, there was no forward movement of the maxillary molars and minimal extrusion of the maxillary molars. These results suggest that onplants can be used as an extremely stable anchorage for maxillary orthopedic facemask treatment.

Factors contributing to the incompatibility between simplified-step adhesives and chemically-cured or dual-cured composites. Part I. Single-step self-etching adhesive.

PURPOSE: To determine if adverse chemical interaction and adhesive permeability are both responsible for the incompatibility between a single-step, self-etching adhesive and chemically-cured or dual-cured composites. MATERIALS AND METHODS: Bonding was performed with Xeno CF Bond (Dentsply-Sankin), on either hydrated (H) or dehydrated (DH) human dentin. For microtensile bond strength evaluation, a dual-cured hybrid composite (Bis-Core) was activated using: (1) the light-cured (L) mode (base syringe only), (2) delayed light activation (DL) (base syringe left on top of cured adhesive in the dark for 20 min before activation), and (3) the chemically-cured (C) mode (base and catalyst syringes in the dark). A chemical co-initiator (B; BondLink) was also applied to the cured adhesive before coupling with the composite in chemically-cured mode. This resulted in seven experimental groups: (1) L-H (control); (2) DL-H; (3) DL-DH; (4) C-H; (5) C-DH; (6) C-B-H; and (7) C-B-DH. For transmission electron microscopy, the dual-cured composite in the seven groups was replaced with a light-cured microfilled composite (Metafil CX) and an experimental chemically-cured microfilled composite of the same composition. Specimens were immersed in ammoniacal silver nitrate for 24 h. After reduction of the diamine silver ions to silver, undemineralized and unstained sections were examined for nanoleakage within the resin-dentin interfaces of the seven groups. RESULTS: For the light-cured modes, bond strengths fell substantially in DL-H but not in DL-DH. For the chemically-cured modes, bond strengths were lowest in C-H and only increased slightly in C-DH. The use of a chemical co-initiator with the adhesive further improved the bond strength in C-B-H. Only C-B-DH was not significantly different from the control light-cured mode L-H. Two abnormal modes of silver deposition were observed in resin-dentin interfaces. A continuous layer of silver was observed when the chemically-cured composite was applied to the cured adhesive in the absence of the chemical co-initiator (C-H; C-DH). Silver-impregnated water blisters were identified when the chemically-cured composite was coupled to bonded hydrated dentin (C-H; C-B-H). Similar water blisters were seen in DL-H in which adverse chemical interaction should not occur. CONCLUSION: Adverse chemical interaction between catalytic components of chemically-cured composite and the tested single-step, self-etching adhesive was the major cause of reductions in bond strength, while adhesive permeability was a minor cause of bond strength reduction. The combination of these two factors accounts for the substantial reduction in bond strength when chemically-cured or dual-cured composites were coupled to bonded hydrated dentin.

The influence of hygroscopic expansion of resin-based restorative materials on artificial gap reduction.

PURPOSE: This study compared the effect of water sorption on the extent of marginal gap reduction in two resin-modified glass-ionomer cements (RMGICs), two giomers, two compomers, and two resin composites over a twelve-week storage period. MATERIALS AND METHODS: Artificial gaps were created in 160 borosilicate glass cylinders. One-half of the internal surface of each cylinder was blocked out with wax and the other half was sandblasted. The bonding surface was further treated with 4% hydrofluoric acid, rinsed, and then coated with silane. After removal of the wax, one coat of dentin adhesive was applied to the silane-treated surface of the cylinder, briefly air dried and light cured. Eight light-cured restorative materials were placed incrementally: Vitremer (V), Fuji II LC (FJ), Beautifil (B), Reactmer Paste (R), Compoglass F (C), F2000 (F), Filtek Z250 (Z), and Tetric-Ceram (T). For each material, ten specimens were stored in deionized water (W), and ten (control) in nonaqueous silicone fluid (O) at 37 degrees C. The dimension of the same maximum gap created in each specimen was repeatedly measured at 0, 1, 2, 4, 6, 8, 10, and 12 weeks. RESULTS: R-W exhibited extensive hygroscopic expansion that resulted in cracking of 40% of glass cylinders after the 2nd week and 70% after the 4th week. One-way ANOVA of the other seven water groups showed significant differences (p < 0.001) among gap widths measured at different time intervals in V-W, FJ-W, C-W, F-W. Both RMGICs had the most significant gap reduction during the first week (p < 0.001). Both compomers exhibited delayed water-sorption characteristics, with more significant gap reduction observed in C-W. B-W was similar to the two resin composites Z-W and T-W and exhibited the least gap reduction. After the first week, there were no significant differences in the percentage reduction in marginal gaps for any of the groups (p > 0.05). CONCLUSION: Marginal gap reduction that results from water sorption is more extensive and rapid in RMG-ICs, followed by compomers, whereas composites are relatively stable. Reactmer Paste exhibits rapid and extensive expansion and should probably be avoided in tooth preparations that involve thin unsupported enamel.

Guidance of eruption for general practitioners.

The principle of early treatment through well-planned extraction of primary teeth followed by removal of permanent teeth has stood the test of time. The objective of this article is to develop some simple guidelines for general dental practitioners to perform 'guidance of eruption' in malocclusion with severe crowding.

Single-step, self-etch adhesives behave as permeable membranes after polymerization. Part III. Evidence from fluid conductance and artificial caries inhibition.

PURPOSE: To test the hypothesis that formation of inhibition zones by bonded restorations in artificially-induced carious dentin lesions is related to the permeability of the self-etch adhesives. METHODS: Fluid conductance of four single-step self-etch adhesives (Prompt L-Pop, Etch&Prime 3.0, One-Up Bond F and Reactmer Bond), and a control two-step self-etch adhesive (UniFil Bond) were measured after sound dentin surfaces were:(1) acid-etched; (2) polished to produce smear layers; (3) bonded with the adhesive; each at 20 cm hydrostatic pressure (hp). Osmotic fluid conductance was also determined for the bonded dentin after immersion in 4.8 M CaCl2 at 0 cm hp. For artificial caries inhibition, a non-fluoride releasing (NFR) two-step self-etch adhesive (UniFil Bond) and a fluoride-releasing (FR) single-step adhesive (Reactmer Bond) were used in combination with a NFR composite (Metafil CX) or a FR restorative material (Reactmer Paste). Artificial caries were induced in these restorations, from which 120 +/- 10 microm thick sections and the effect of caries inhibition were quantitatively assessed with polarizing light microscopy and image analysis. RESULTS: Fluid conductance after bonding with the single-step adhesives Prompt L-Pop and Etch&Prime 3.0 were not significantly different from those recorded from smear layer-covered dentin. Although better seals were achieved with One-Up Bond F and Reactmer Bond, fluid conductance at 20 cm hp was significantly higher than the two-step self-etch adhesive UniFil Bond. Osmotic conductance at 0 cm hp were not significantly different from normal fluid conductance at 20 cm hp. The sizes of artificial carious lesions in UniFil Bond were significantly higher irrespective of whether a FR or NFR composite was used. Significant reduction in lesion size occurred in Reactmer Bond with the use of a NFR composite, and even more so with the use of a FR composite.

Clinical evaluation of Dyract AP restorative in permanent molars: 2-year results.

PURPOSE: To evaluate the clinical behavior of a compomer restorative system, Dyract AP, placed in combination with Non-Rinse Conditioner and Prime&Bond NT in permanent posterior teeth. MATERIALS AND METHODS: Fifty Class II and 41 Class I restorations were placed in 39 patients in a dental teaching hospital. The restorations were evaluated directly at baseline and after 6, 12 and 24 months using the modified USPHS-Ryge criteria. Clinical photographs, polyvinylsiloxane impressions and bitewing radiographs of each restoration were taken for indirect assessment. RESULTS: After 2 years, all 76 restorations were evaluated in situ. Color matching ability and surface characteristics were excellent. A gradual deterioration in marginal discoloration and marginal integrity was noted. The percentages of Alfa scores for each criterion at the 24-month evaluation were: color match 96%, marginal discoloration 50%, marginal integrity 26%, anatomic form 97% and surface texture 95%. Five of the restorations (6%) had experienced partial fracture or recurrent caries. After 6, 12 and 24 months, the net mean occlusal wear values were 18.5 microm, 35.7 microm and 55.9 microm, respectively. There was no statistically significant difference between Class I and II restorations for each criterion (Fisher's exact test, P > 0.05).

Tensile strength and ultrastructure of a compomer and a composite in aqueous and non-aqueous storage media.

PURPOSE: To compare the ultimate tensile strength (UTS) of a compomer (Dyract AP) and a composite (Spectrum TPH) that were stored in an aqueous or a non-aqueous medium for up to 180 days. METHODS: 156 hourglass-shaped specimens of each material with cylindrical cross-sectional areas along the test regions were prepared. For each material, 12 beams were stressed to failure using a microtensile testing method to obtain the baseline UTS data. The rest were divided into two groups. One group was stored in de-ionized water (W), and the other (control) in silicone fluid (O) at 37 degrees C. 12 beams were removed from the respective storage medium after 1, 7, 14, 30, 90, 180 days for evaluation of the NTS. Materials retrieved from the intact central cylindrical portion of the fractured 180-day specimens were prepared for transmission electron microscopy (TEM). RESULTS: Baseline UTS for Dyract AP (D) and Spectrum TPH (S) were 76 +/- 16 MPa and 92 +/- 13 MPa, respectively. One-way ANOVA on ranks and Dunn's multiple comparison tests showed that UTS of Groups D-O, S-O and S-W remained stable during 180 days and were not significantly different from the baseline results. There was a significant drop in UTS in Group D-W after 90 and 180 days when compared with the 1-day result (P < 0.05). A highly significant nonlinear correlation was also observed in Group D-W between the mean UTS after the first day and the storage time (P < 0.01). No difference could be seen between the filler-matrix interface in S-O and S-W. A very thin glass-ionomer phase (ca. 200 nm thick siliceous hydrogel layer) could be observed in D-W, but not in D-O.

CT findings in small bowel angioedema: a cause of acute abdominal pain.

A patient who presented with acute abdominal pain secondary to small bowel angioedema is reported. Characteristic imaging features are highlighted with clarifying images. The importance of considering this diagnosis in patients presenting with acute abdominal pain correlated with the appropriate history is discussed.