Cleft complications: Severely rotated maxillary permanent central incisors.

The maxillary permanent central incisor (MPCI) has been reported to be rotated in up to 96% of cleft patients. A severely rotated MPCI is highly visible when smiling, drawing attention to a repaired cleft lip, and is often the main presenting complaint of a patient with cleft lip and palate attending for orthodontic treatment. The benefit of interceptive orthodontic treatment to alleviate these concerns must be weighed up against the consequences of adding to the already substantial orthodontic burden likely to be faced by these patients.Despite the high prevalence of this dental abnormality among cleft patients, there is little published in the literature regarding this type of malocclusion. This paper explores the aetiology, presentation and management of this condition, using examples from cases treated within our department. In addition, the commonly found pre-existing anomaly of a short root length is discussed, in combination with the implications this may have upon orthodontic treatment planning for a rotated MPCI.

Global Proteotoxicity Caused by Human ß2 Microglobulin Variants Impairs the Unfolded Protein Response in C. elegans.

Aggregation of ß2 microglobulin (ß2m) into amyloid fibrils is associated with systemic amyloidosis, caused by the deposition of amyloid fibrils containing the wild-type protein and its truncated variant, ΔN6 ß2m, in haemo-dialysed patients. A second form of familial systemic amyloidosis caused by the ß2m variant, D76N, results in amyloid deposits in the viscera, without renal dysfunction. Although the folding and misfolding mechanisms of ß2 microglobulin have been widely studied in vitro and in vivo, we lack a comparable understanding of the molecular mechanisms underlying toxicity in a cellular and organismal environment. Here, we established transgenic C. elegans lines expressing wild-type (WT) human ß2m, or the two highly amyloidogenic naturally occurring variants, D76N ß2m and ΔN6 ß2m, in the C. elegans bodywall muscle. Nematodes expressing the D76N ß2m and ΔN6 ß2m variants exhibit increased age-dependent and cell nonautonomous proteotoxicity associated with reduced motility, delayed development and shortened lifespan. Both ß2m variants cause widespread endogenous protein aggregation contributing to the increased toxicity in aged animals. We show that expression of ß2m reduces the capacity of C. elegans to cope with heat and endoplasmic reticulum (ER) stress, correlating with a deficiency to upregulate BiP/hsp-4 transcripts in response to ER stress in young adult animals. Interestingly, protein secretion in all ß2m variants is reduced, despite the presence of the natural signal sequence, suggesting a possible link between organismal ß2m toxicity and a disrupted ER secretory metabolism.

Assessment of slot sizes in self-ligating brackets using electron microscopy.

OBJECTIVE: To measure the slot dimensions of 0.022 inch self-ligating upper central incisor brackets from six manufacturers using electron microscopy, to compare the measured dimensions with the manufacturers' published dimensions, and to determine if the walls of the slots were parallel. MATERIALS: Six self-ligating upper central incisor brackets from four manufacturers (SmartClip and Clarity SL, 3M Unitek, Monrovia, CA, USA; Speed, Strite Industries Ontario, Canada; Damon MX, Ormco, Orange, CA, USA; In-Ovation R and In-Ovation C, Dentsply GAC, Bohemia NY, USA) were imaged with a scanning electron microscope and the slots heights measured. Intra-operator repeatability and accuracy were determined. RESULTS: All brackets had slot sizes that were significantly larger (p < 0.05) than the stated 0.022 inch. Speed brackets were 5.1 per cent larger (0.02311 inch) and the closest to the published dimension. The SmartClip brackets were 14.8 per cent larger (0.02526 inch) than the quoted slot size of 0.022 inch. In most brackets the distances between the slot walls was generally greater further from the bracket bases. CONCLUSIONS: The actual measurements of upper central incisor self-ligating brackets from six manufacturers were larger than the manufacturers' stated dimension, and the walls of the slots diverged from the bracket bases.

Increased levels of Stress-inducible phosphoprotein-1 accelerates amyloid-ß deposition in a mouse model of Alzheimer's disease.

Molecular chaperones and co-chaperones, which are part of the protein quality control machinery, have been shown to regulate distinct aspects of Alzheimer's Disease (AD) pathology in multiple ways. Notably, the co-chaperone STI1, which presents increased levels in AD, can protect mammalian neurons from amyloid-ß toxicity in vitro and reduced STI1 levels worsen Aß toxicity in C. elegans. However, whether increased STI1 levels can protect neurons in vivo remains unknown. We determined that overexpression of STI1 and/or Hsp90 protected C. elegans expressing Aß(3-42) against Aß-mediated paralysis. Mammalian neurons were also protected by elevated levels of endogenous STI1 in vitro, and this effect was mainly due to extracellular STI1. Surprisingly, in the 5xFAD mouse model of AD, by overexpressing STI1, we find increased amyloid burden, which amplifies neurotoxicity and worsens spatial memory deficits in these mutants. Increased levels of STI1 disturbed the expression of Aß-regulating enzymes (BACE1 and MMP-2), suggesting potential mechanisms by which amyloid burden is increased in mice. Notably, we observed that STI1 accumulates in dense-core AD plaques in both 5xFAD mice and human brain tissue. Our findings suggest that elevated levels of STI1 contribute to Aß accumulation, and that STI1 is deposited in AD plaques in mice and humans. We conclude that despite the protective effects of STI1 in C. elegans and in mammalian cultured neurons, in vivo, the predominant effect of elevated STI1 is deleterious in AD.

A short motif in the N-terminal region of α-synuclein is critical for both aggregation and function.

Aggregation of human α-synuclein (αSyn) is linked to Parkinson's disease (PD) pathology. The central region of the αSyn sequence contains the non-amyloid ß-component (NAC) crucial for aggregation. However, how NAC flanking regions modulate αSyn aggregation remains unclear. Using bioinformatics, mutation and NMR, we identify a 7-residue sequence, named P1 (residues 36-42), that controls αSyn aggregation. Deletion or substitution of this 'master controller' prevents aggregation at pH 7.5 in vitro. At lower pH, P1 synergises with a sequence containing the preNAC region (P2, residues 45-57) to prevent aggregation. Deleting P1 (ΔP1) or both P1 and P2 (ΔΔ) also prevents age-dependent αSyn aggregation and toxicity in C. elegans models and prevents αSyn-mediated vesicle fusion by altering the conformational properties of the protein when lipid bound. The results highlight the importance of a master-controller sequence motif that controls both αSyn aggregation and function-a region that could be targeted to prevent aggregation in disease.

The impact of idealised facial images on satisfaction with facial appearance: comparing 'ideal' and 'average' faces.

OBJECTIVES: Recent work has demonstrated that female orthognathic patients display more dissatisfaction with their facial appearance after viewing idealised images of facial photographs, than do controls. Patients may request orthognathic surgery because they hope to improve their appearance to conform with ideals portrayed in the mass media, and these hopes may not be realistic. Patients who demonstrate certain personality traits are more likely to hold such hopes. The current study sought to identify the role of dental status (orthognathic patient versus control), personality traits and media images in dissatisfaction with facial appearance. METHODS: Female patients and controls completed a bank of personality measures and then gave repeated measures of satisfaction with their facial appearance after viewing images of 'ideal' and 'average' women. RESULTS: Neither group showed any change in satisfaction with appearance after viewing either set of images. Patients showed lower satisfaction with facial appearance than controls, but did not differ on other personality measures. CONCLUSIONS: Viewing 'ideal' images of other women has no significant impact on satisfaction with appearance compared to viewing images of 'average' women. These results may help inform the development of a psycho-educational intervention to protect women against the negative effects of viewing idealised images in the media.

A PQM-1-Mediated Response Triggers Transcellular Chaperone Signaling and Regulates Organismal Proteostasis.

In metazoans, tissues experiencing proteotoxic stress induce "transcellular chaperone signaling" (TCS) that activates molecular chaperones, such as hsp-90, in distal tissues. How this form of inter-tissue communication is mediated to upregulate systemic chaperone expression and whether it can be utilized to protect against protein misfolding diseases remain open questions. Using C. elegans, we identified key components of a systemic stress signaling pathway that links the innate immune response with proteostasis maintenance. We show that mild perturbation of proteostasis in the neurons or the intestine activates TCS via the GATA zinc-finger transcription factor PQM-1. PQM-1 coordinates neuron-activated TCS via the innate immunity-associated transmembrane protein CLEC-41, whereas intestine-activated TCS depends on the aspartic protease ASP-12. Both TCS pathways can induce hsp-90 in muscle cells and facilitate amelioration of Aß3-42-associated toxicity. This may have powerful implications for the treatment of diseases related to proteostasis dysfunction.

A computerized photographic assessment of the relationship between skeletal discrepancy and mandibular outline asymmetry.

The aim of this study was to investigate the relationship between mandibular outline asymmetry and skeletal discrepancy in a sample of orthodontic patients (33 females, 33 males) aged from 8 to 19 years. Skeletal discrepancy was assessed in both the anteroposterior and vertical planes, using standard cephalometric analyses. All were photographed under standardized conditions and the photographs were then digitized for analysis using a computerized system to assess differences in four variables (area, perimeter, compactness and moment-ratio) between the right and left sides of the mandibular outline. The results showed good repeatability of the photographic, cephalometric and digitization methods. A statistically significant relationship was found between mandibular outline asymmetry and both anteroposterior and vertical skeletal discrepancy in this sample, when compared with patients with an average skeletal pattern. There appeared to be a statistically significant relationship between a reduced ANB angle (< 3 degrees) and mandibular outline asymmetry (P = 0.051), as well as between an increase in lower face height and mandibular asymmetry (P = 0.023).