Repeat length and RNA expression level are not primary determinants in CUG expansion toxicity in Drosophila models.

Evidence for an RNA gain-of-function toxicity has now been provided for an increasing number of human pathologies. Myotonic dystrophies (DM) belong to a class of RNA-dominant diseases that result from RNA repeat expansion toxicity. Specifically, DM of type 1 (DM1), is caused by an expansion of CUG repeats in the 3'UTR of the DMPK protein kinase mRNA, while DM of type 2 (DM2) is linked to an expansion of CCUG repeats in an intron of the ZNF9 transcript (ZNF9 encodes a zinc finger protein). In both pathologies the mutant RNA forms nuclear foci. The mechanisms that underlie the RNA pathogenicity seem to be rather complex and not yet completely understood. Here, we describe Drosophila models that might help unravelling the molecular mechanisms of DM1-associated CUG expansion toxicity. We generated transgenic flies that express inducible repeats of different type (CUG or CAG) and length (16, 240, 480 repeats) and then analyzed transgene localization, RNA expression and toxicity as assessed by induced lethality and eye neurodegeneration. The only line that expressed a toxic RNA has a (CTG)(240) insertion. Moreover our analysis shows that its level of expression cannot account for its toxicity. In this line, (CTG)(240.4), the expansion inserted in the first intron of CG9650, a zinc finger protein encoding gene. Interestingly, CG9650 and (CUG)(240.4) expansion RNAs were found in the same nuclear foci. In conclusion, we suggest that the insertion context is the primary determinant for expansion toxicity in Drosophila models. This finding should contribute to the still open debate on the role of the expansions per se in Drosophila and in human pathogenesis of RNA-dominant diseases.

Cultivation and expansion of canine Schwann cells using reexplantation

Despite the numerous available possibilities for the surgical treatment of peripheral nerve lesions found in the dog, the success of these treatments is often unsatisfactory. It has been proven that Schwann cells (SC) have a positive influence on the regeneration of nerve stumps. Implanting a guidance channel seeded with autologous SC at the lesion site could be a new therapeutic approach. The aim of this research was to investigate the in vitro cultivation and expansion of canine SC as the main requirement for the treatment referred to above. Biopsies were carried out on 17 nerve samples originating from dogs of different breed, age, gender and condition. The reexplantation method was employed, followed by dissociation using hyaluronidase, collagenase and trypsin and further expansion. The samples were divided into six groups which were treated with a varying combination of mitogens (forskolin, bovine PEX, choleratoxin, heregulin). To obtain the quantities of SC, the specimens were immunostained by a p75-antibody. By employing a growing number of agents it was possible to obtain an increase in both the quantity of cells and purity of cultures. A maximum of 16x10(5) cells per millilitre of suspension was achieved. The largest SC purity measured 27.1%. The maximum SC quantity achieved was 43.3x10(4) SC per millilitre.

Does the maxillary midline diastema close after frenectomy?

OBJECTIVE To analyze the closure, persistence or reopening of the maxillary midline diastema after frenectomy in patients with and without subsequent orthodontic treatment. METHOD AND MATERIALS All patients undergoing frenectomy with a CO2 laser were included in this retrospective study during the period of September 2002 to June 2011. Age and sex, the dimension of the diastema, eruption status of the maxillary canines, and the presence of an orthodontic treatment were recorded at the day of frenectomy and during follow-up. RESULTS Of the 59 patients fulfilling the inclusion criteria, 31 (52.5%) had an active orthodontic therapy, while 27 (45.8%) had a frenectomy without orthodontic treatment. For one patient, information concerning orthodontic treatment was not available. In the first follow-up (2 to 12 weeks), only four diastemas closed after frenectomy and orthodontic treatment, and none after frenectomy alone. In the second follow-up (4 to 19 months), statistically significantly (P = .002) more diastemas (n = 20) closed with frenectomy and orthodontic treatment than with frenectomy alone (n = 3). At the long-term (21 to 121 months) follow-up, only four patients had a persisting diastema, and in three patients orthodontic treatment was ongoing. CONCLUSION Closure of the maxillary midline diastema with a prominent frenum is more predictable with frenectomy and concomitant orthodontic treatment than with frenectomy alone. This study demonstrates the importance of an interdisciplinary approach to treat maxillary midline diastemas, ideally including general practitioners, oral surgeons, periodontists, and orthodontists.

Indication and timing of soft tissue augmentation at maxillary and mandibular incisors in orthodontic patients. A systematic review.

OBJECTIVE To assess the indication and timing of soft tissue augmentation for prevention or treatment of gingival recession when a change in the inclination of the incisors is planned during orthodontic treatment. MATERIALS AND METHODS Electronic database searches of literature were performed. The following electronic databases with no restrictions were searched: MEDLINE, EMBASE, Cochrane, and CENTRAL. Two authors performed data extraction independently using data collection forms. RESULTS No randomized controlled trial was identified. Two studies of low-to-moderate level of evidence were included: one of prospective and retrospective data collection and one retrospective study. Both implemented a periodontal intervention before orthodontics. Thus, best timing of soft tissue augmentation could not be assessed. The limited available data from these studies appear to suggest that soft tissue augmentation of bucco-lingual gingival dimensions before orthodontics may yield satisfactory results with respect to the development or progression of gingival recessions. However, the strength of the available evidence is not adequate in order to change or suggest a possible treatment approach in the daily practice based on solid scientific evidence. CONCLUSIONS Despite the clinical experience that soft tissue augmentation of bucco-lingual gingival dimensions before orthodontic treatment may be a clinically viable treatment option in patients considered at risk, this treatment approach is not based on solid scientific evidence. Moreover, the present data do not allow to draw conclusions on the best timing of soft tissue augmentation when a change in the inclination of the incisors is planned during orthodontic treatment and thus, there is a stringent need for randomized controlled trials to clarify these open issues.

Localization of impacted maxillary canines and root resorption of neighbouring teeth: a study assessing the diagnostic value of panoramic radiographs in two groups of observers.

OBJECTIVES To assess the diagnostic value of panoramic views (2D) of patients with impacted maxillary canines by a group of trained orthodontists and oral surgeons, and to quantify the subjective need and reasons for further three-dimensional (3D) imaging. MATERIALS AND METHODS The study comprises 60 patients with panoramic radiographs (2D) and cone beam computed tomography (CBCT) scans (3D), and a total of 72 impacted canines. Data from a standardized questionnaire were compared within (intragroup) and between (intergroup) a group of orthodontists and oral surgeons to assess possible correlations and differences. Furthermore, the questionnaire data were compared with the findings from the CBCT scans to estimate the correlation within and between the two specialties. Finally, the need and reasons for further 3D imaging was analysed for both groups. RESULTS When comparing questionnaire data with the analysis of the respective CBCT scans, orthodontists showed probability (Pr) values ranging from 0.443 to 0.943. Oral surgeons exhibited Pr values from 0.191 to 0.946. Statistically significant differences were found for the labiopalatal location of the impacted maxillary canine (P = 0.04), indicating a higher correlation in the orthodontist group. The most frequent reason mentioned for the further need of 3D analysis was the labiopalatal location of the impacted canines. Oral surgeons were more in favour of performing further 3D imaging (P = 0.04). CONCLUSIONS Orthodontists were more likely to diagnose the exact labiopalatal position of impacted maxillary canines when using panoramic views only. Generally, oral surgeons more often indicated the need for further 3D imaging.

The timing of significant arch dimensional changes with fixed orthodontic appliances: data from a multicenter randomised controlled trial.

OBJECTIVES To identify the timing of significant arch dimensional increases during orthodontic alignment involving round and rectangular nickel-titanium (NiTi) wires and rectangular stainless steel (SS). A secondary aim was to compare the timing of changes occurring with conventional and self-ligating fixed appliance systems. METHODS In this non-primary publication, additional data from a multicenter randomised trial initially involving 96 patients, aged 16 years and above, were analysed. The main pre-specified outcome measures were the magnitude and timing of maxillary intercanine, interpremolar, and intermolar dimensions. Each participant underwent alignment with a standard Damon (Ormco, Orange, CA) wire sequence for a minimum of 34 weeks. Blinding of clinicians and patients was not possible; however, outcome assessors and data analysts were kept blind to the appliance type during data analysis. RESULTS Complete data were obtained from 71 subjects. Significant arch dimensional changes were observed relatively early in treatment. In particular, changes in maxillary inter-first and second premolar dimensions occurred after alignment with an 0.014in. NiTi wire (P<0.05). No statistical differences in transverse dimensions were found between rectangular NiTi and working SS wires for each transverse dimension (P>0.05). Bracket type had no significant effect on the timing of the transverse dimensional changes. CONCLUSIONS Arch dimensional changes were found to occur relatively early in treatment, irrespective of the appliance type. Nickel-titanium wires may have a more profound effect on transverse dimensions than previously believed. CLINICAL SIGNIFICANCE On the basis of this research orthodontic expansion may occur relatively early in treatment. Nickel-titanium wires may have a more profound effect on transverse dimensions than previously believed.

Maxillary sinus grafting with a synthetic, nanocrystalline hydroxyapatite-silica gel in humans: histologic and histomorphometric results.

The aim of this study was to evaluate in humans the amount of new bone after sinus floor elevation with a synthetic bone substitute material consisting of nanocrystalline hydroxyapatite embedded in a highly porous silica gel matrix. The lateral approach was applied in eight patients requiring sinus floor elevation to place dental implants. After elevation of the sinus membrane, the cavities were filled with 0.6-mm granules of nanocrystalline hydroxyapatite mixed with the patient's blood. A collagen membrane (group 1) or a platelet-rich fibrin (PRF) membrane (group 2) was placed over the bony window. After healing periods between 7 and 11 months (in one case after 24 months), 16 biopsy specimens were harvested with a trephine bur during implant bed preparation. The percentage of new bone, residual filler material, and soft tissue was determined histomorphometrically. Four specimens were excluded from the analysis because of incomplete biopsy removal. In all other specimens, new bone was observed in the augmented region. For group 1, the amount of new bone, residual graft material, and soft tissue was 28.7% ± 5.4%, 25.5% ± 7.6%, and 45.8% ± 3.2%, respectively. For group 2, the values were 28.6% ± 6.90%, 25.7% ± 8.8%, and 45.7% ± 9.3%, respectively. All differences between groups 1 and 2 were not statistically significant. The lowest and highest values of new bone were 21.2% and 34.1% for group 1 and 17.4% and 37.8% for group 2, respectively. The amount of new bone after the use of nanocrystalline hydroxyapatite for sinus floor elevation in humans is comparable to values found in the literature for other synthetic or xenogeneic bone substitute materials. There was no additional beneficial effect of the PRF membrane over the non-cross-linked collagen membrane.

Evaluation of a new experimental model to study bone healing after ridge expansion with simultaneous implant placement--a pilot study in minipigs.

OBJECTIVE To evaluate the suitability of a minipig model for the study of bone healing and osseointegration of dental implants following bone splitting and expansion of narrow ridges. MATERIAL AND METHODS In four minipigs, the mandibular premolars and first molars were extracted together with removal of the buccal bone plate. Three months later, ridge splitting and expansion was performed with simultaneous placement of three titanium implants per quadrant. On one side of the mandible, the expanded bone gap between the implants was filled with an alloplastic biphasic calcium phosphate (BCP) material, while the gap on the other side was left unfilled. A barrier membrane was placed in half of the quadrants. After a healing period of 6 weeks, the animals were sacrificed for histological evaluation. RESULTS In all groups, no bone fractures occurred, no implants were lost, all 24 implants were osseointegrated, and the gap created by bone splitting was filled with new bone, irrespective of whether BCP or a barrier membrane was used. Slight exposure of five implants was observed, but did not lead to implant loss. The level of the most coronal bone-to-implant contact varied without being dependent on the use of BCP or a barrier membrane. In all groups, the BCP particles were not present deep in the bone-filled gap. However, BCP particles were seen at the crestal bone margin, where they were partly integrated in the new bone. CONCLUSIONS This new minipig model holds great promise for studying experimental ridge splitting/expansion. However, efforts must be undertaken to reduce implant exposure and buccal bone resorption.

Incidence of anatomical variations and disease of the maxillary sinuses as identified by cone beam computed tomography: a systematic review.

PURPOSE To analyze available evidence on the incidence of anatomical variations or disease of the maxillary sinuses as identified by cone beam computed tomography (CBCT) in dentistry. MATERIALS AND METHODS A focused question was developed to search the electronic databases MEDLINE, EMBASE, the Cochrane Oral Health Group Trials Register, and CENTRAL and identify all relevant papers published between 1980 and January 19, 2013. Unpublished literature at ClinicalTrials.gov, in the National Research Register, and in the Pro-Quest Dissertation Abstracts and Thesis database was also included. Studies were included irrespective of language. These results were supplemented by hand and gray literature searches. RESULTS Twenty-two studies were identified. Twenty were retrospective cohort studies, one was a prospective cohort study, and one was a case control study. The main indication for CBCT was dental implant treatment planning, and the majority of studies used a small field of view for imaging. The most common anatomical variations included increased thickness of the sinus membrane, the presence of sinus septa, and pneumatization. Reported sinus disease frequency varied widely, ranging from 14.3% to 82%. There was a wide range in the reported prevalence of mucosal thickening related to apical pathology, the degree of lumenal opacification, features of sinusitis, and the presence of retention cysts and polyps. More pathologic findings in the maxillary sinus were reported in men than in women, and the medial wall and sinus floor were most frequently affected. CONCLUSION CBCT is used primarily to evaluate bony anatomy and to screen for overt pathology of the maxillary sinuses prior to dental implant treatment. Differences in the classification of mucosal findings are problematic in the consistent and valid assessment of health and disease of the maxillary sinus.

Proximity of premolar roots to maxillary sinus: a radiographic survey using cone-beam computed tomography.

INTRODUCTION The proximity of the roots of the posterior maxillary teeth to the maxillary sinus is a constant challenge to the dental practitioner. Because the majority of studies have assessed the relationship regarding molars, the present study focused on premolars. METHODS Cone-beam computed tomographic images of 192 patients were reconstructed in sagittal, coronal, and axial planes to quantify the distances between the root apices of the maxillary premolars and the adjacent maxillary sinus. Measurements were taken for each root, and data were correlated with age, sex, side, and presence of both or absence of 1 of the 2 premolars. RESULTS A total of 296 teeth (177 first and 119 second premolars) were evaluated. The mean distances from buccal roots of the first premolars to the border of the maxillary sinus in the sagittal, coronal, and axial planes ranged from 5.15 ± 2.99 to 8.28 ± 6.27 mm. From palatal roots, the mean distances ranged from 4.20 ± 3.69 to 7.17 ± 6.14 mm. The mean distances of second premolars were markedly shorter in buccal roots between 2.32 ± 2.19 and 3.28 ± 3.17 mm and in palatal roots between 2.68 ± 3.58 and 3.80 ± 3.71 mm, respectively. The frequency of a premolar root protrusion into the maxillary sinus was very low in first premolars (0%-7.2%) but higher in second premolars (2.5%-13.6%). Sex, age, side, and presence/absence of premolars failed to significantly influence the mean distances between premolar roots and the maxillary sinus. CONCLUSIONS Based on the calculated mean distances of the present study, only few premolars (and if so second premolars) would present a risk of violating the border of the maxillary sinus during conventional or surgical endodontic treatment or in case of tooth extraction.

Patient-reported outcomes of maxillary implant-supported overdentures compared with conventional dentures

OBJECTIVE The aim of the present prospective clinical study was to compare patient-reported outcomes for maxillary conventional dentures and maxillary implant-supported dentures. MATERIAL AND METHODS Twenty-one patients (6 women and 15 men) being edentulous in the maxilla and encountering problems with their existing dentures were included. Twelve patients (4 women and 8 men) received a new set of conventional dentures, due to insufficient dentures. In nine patients (2 women and 7 men), the existing dentures were adjusted by means of relining or rebasing. All patients received implant-supported dentures on two retentive anchors. In total, 42 implants were inserted in the anterior maxilla. The participants rated their satisfaction on their existing conventional dentures, 2 months after insertion of new conventional dentures and 2 months after insertion of implant-supported dentures. Thereby, patients responded to questionnaires capturing the oral health impact profile (OHIP) using visual analog scales. Seven domains (functional limitation, physical pain, psychological discomfort, physical, psychological and social disability and handicap) were assessed. Higher scores implied poorer patient satisfaction. In addition, the questionnaire involved the evaluation of cleaning ability, general satisfaction, speech, comfort, esthetics, stability, and chewing ability. Higher scores implied higher patient satisfaction. RESULTS Patient satisfaction significantly increased for implant-supported dentures compared with old dentures in all seven OHIP subgroups, as well as for cleaning ability, general satisfaction, ability to speak, comfort, esthetics, and stability (P < 0.05). The comparison of new conventional dentures and implant-supported dentures revealed a statistically significantly increased satisfaction for functional limitation (difference of 33.2 mm), psychological discomfort (difference of 36.7 mm), physical disability (difference of 36.3 mm), and social disability (difference of 23.5 mm), (P < 0.05). Additionally, general satisfaction, chewing ability, speech, and stability significantly improved in implant-supported dentures (P < 0.05). CONCLUSIONS Within the limits of this study, maxillary dentures retained by two implants provided some significant short-term improvements over conventional dentures in oral- and health-related quality of life.

Morphologic characteristics, location, and associated complications of maxillary and mandibular supernumerary teeth as evaluated using cone beam computed tomography.

OBJECTIVES To evaluate the location and morphologic characteristics of supernumerary teeth and to assess the frequency and extent of root resorption of adjacent teeth using cone beam computed tomography (CBCT). MATERIALS AND METHODS CBCT scans of 82 patients with supernumerary teeth in the maxilla and mandible were evaluated by two orthodontists independently. Data regarding the type, shape, and three-dimensional (3D) location of the supernumeraries including the frequency and extent of root resorption of adjacent teeth were recorded and evaluated for possible associations. RESULTS The study comprised a total of 101 supernumerary teeth. Most of the patients (80.5 per cent) exhibited one single supernumerary tooth, while 15.8 per cent had two and 3.7 per cent had three supernumeraries. Males were affected more than females with a ratio of 1.65:1. Mesiodentes were the most frequently diagnosed type of supernumerary teeth (48.52 per cent), followed by supernumerary premolars (23.76 per cent) and lateral incisors (18.81 per cent). Supernumeraries were most commonly conical in shape (42.6 per cent) with a normal or inclined vertical position (61.4 per cent). Root resorption of adjacent teeth was detected for 22.8 per cent of the supernumerary teeth, most frequently for supernumerary premolars. There was a significant association between root resorption of adjacent teeth and type and shape of tooth. Interrater agreement for the measurements performed showed kappa values ranging from 0.55 to 1 with a kappa value of 1 for type and shape of the supernumerary teeth. CONCLUSIONS CBCT provides 3D information about location and shape of supernumerary teeth as well as prevalence and degree of root resorption of neighbouring teeth with moderate to high interrater correlation.