7 research outputs found
study protocol for a randomized controlled trial
Background For treating deep caries lesions, selective or stepwise (one- and
two-step) incomplete excavation seems advantageous compared with complete
caries removal. However, current evidence regarding the success, as defined by
not requiring any retreatments, or survival of teeth after different
excavations is insufficient for definitive recommendation, especially when
treating deciduous teeth. Moreover, restoration integrity has not been
comparatively analyzed longitudinally, and neither patients’, dentists’ or
parents’ preferences nor the clinical long-term costs emanating from both
initial and retreatments have been reported yet. Methods/Design The planned
study is a prospective multicenter, two-arm parallel group, randomized
controlled clinical trial comparing selective and stepwise excavation in
deciduous molars with deep, active caries lesions without pulpal symptoms. We
will recruit 300 children aged between three and nine-years-old with a minimum
of one such molar. Patients participating in another study, or those with
systemic diseases, disabilities or known allergies to used materials as well
patients with teeth expected to exfoliate within the next 18 months will be
excluded. After inclusion, sequence generation will be performed. Initial
treatment will follow dental routine. During excavation, leathery, moist and
reasonably soft dentin will be left in proximity to the pulp followed by
adhesive restoration of the cavity. Afterwards, patients’, dentists’ and
parents’ subjective assessment of the treatment will be recorded using visual
analogue or Likert scales. Re-examination will be performed after six months,
and only then teeth will be allocated to one of the two interventions.
Selectively excavated teeth will not be treated further, whilst for stepwise
caries removal, a second excavation will be performed until only hard dentin
remains. Clinical re-evaluations will be performed after 12, 24 and 36 months.
Restorations will be reassessed using modified Ryge criteria. Objectively or
subjectively required retreatments will determine success and survival.
Retreatments will be evaluated both subjectively and regarding generated
costs. Discussion Based on the results of the trial, decision-making for
treating deep caries lesions in deciduous molars based on multiple criteria
should be feasible
Salivary and pellicle proteome: A datamining analysis
We aimed to comprehensively compare two compartmented oral proteomes, the salivary and the dental pellicle proteome. Systematic review and datamining was used to obtain the physico-chemical, structural, functional and interactional properties of 1,515 salivary and 60 identified pellicle proteins. Salivary and pellicle proteins did not differ significantly in their aliphatic index, hydrophaty, instability index, or isoelectric point. Pellicle proteins were significantly more charged at low and high pH and were significantly smaller (10-20 kDa) than salivary proteins. Protein structure and solvent accessible molecular surface did not differ significantly. Proteins of the pellicle were more phosphorylated and glycosylated than salivary proteins. Ion binding and enzymatic activities also differed significantly. Protein-protein-ligand interaction networks relied on few key proteins. The identified differences between salivary and pellicle proteins could guide proteome compartmentalization and result in specialized functionality. Key proteins could be potential targets for diagnostic or therapeutic application
Treatment of deep caries lesions: a multi-center randomised controlled trial using a comprehensive set of outcome parameters
LASP1 is a novel BCR-ABL substrate and a phosphorylation-dependent binding partner of CRKL in chronic myeloid leukemia
Chronic myeloid leukemia (CML) is characterized by a genomic translocation generating a permanently active BCR-ABL oncogene with a complex pattern of atypically tyrosine-phosphorylated proteins that drive the malignant phenotype of CML. Recently, the LIM and SH3 domain protein 1 (LASP1) was identified as a component of a six gene signature that is strongly predictive for disease progression and relapse in CML patients. However, the underlying mechanisms why LASP1 expression correlates with dismal outcome remained unresolved.
Here, we identified LASP1 as a novel and overexpressed direct substrate of BCR-ABL in CML. We demonstrate that LASP1 is specifically phosphorylated by BCR-ABL at tyrosine-171 in CML patients, which is abolished by tyrosine kinase inhibitor therapy. Further studies revealed that LASP1 phosphorylation results in an association with CRKL - another specific BCR-ABL substrate and bona fide biomarker for BCR-ABL activity. pLASP1-Y171 binds to non-phosphorylated CRKL at its SH2 domain. Accordingly, the BCR-ABL-mediated pathophysiological hyper-phosphorylation of LASP1 in CML disrupts normal regulation of CRKL and LASP1, which likely has implications on downstream BCR-ABL signaling. Collectively, our results suggest that LASP1 phosphorylation might serve as an additional candidate biomarker for assessment of BCR-ABL activity and provide a first step toward a molecular understanding of LASP1 function in CML