Type II c-Met inhibitors: molecular insight into crucial interactions for effective inhibition.

The c-Met tyrosine kinase plays an important role in human cancers. Preclinical studies demonstrated that c-Met is over-expressed, mutated and amplified in a variety of human tumor types and design of more potent c-Met inhibitors is a priority. In this study, 14 molecular dynamics simulations of potent type II c-Met inhibitors were run to resolve the critical interactions responsible for high affinity of ligands towards c-Met considering the essential flexibility of protein-ligand interactions. Residues Phe1223 and Tyr1159, involved in pi-pi interactions were recognized as the most effective residues in the ligand binding in terms of binding free energies. Hydrogen bond interaction with Met1160 was also found necessary for effective type II ligand binding to c-Met.

Impact of Parents' Sense of Coherence on Children's Oral Health-Related Behaviors and Dental Caries Experience among Newcomers.

PURPOSE: To examine the relationship between parents' sense of coherence (SOC) and children's oral health outcomes among newcomers (immigrants to Canada). METHODS: Immigrant parents with children aged 1-12 years who lived in Canada for 10 years or less were recruited. Outcome variables included children's caries experience (DMFT/dmft) and oral health-related behaviors (frequency of toothbrushing, sugar intake, and dental visits). Parents SOC was measured. RESULTS: Among 274 parents: mean (SD) age 34.92 (6.35) years; 57% post-secondary education; 38% monthly income below $2000; and 41% living in Canada for less than five years. Children: mean (SD) age 4.5 (2.9) years; 55% born in Canada; 42% dental coverage; 52% untreated caries. The mean (SD) of parents' SOC was 59.1 (12.03). Sense of coherence scores were not significantly associated with children's caries experience and oral health behaviors. CONCLUSIONS: Parent's SOC was relatively low among newcomers and not associated with children's oral health outcomes.

Modeling the Theory of Planned Behaviour to predict adherence to preventive dental visits in preschool children.

OBJECTIVES: Dental caries is the most common chronic childhood disease that occurs in a continuum and can be prevented by children and their parents' adherence to recommended oral health behaviors. Theory-driven tools help practitioners to identify the causes for poor adherence and develop effective interventions. This study examined the Expanded Theory of Planned Behaviour (TPB) Model by adding the concept of Sense of Coherence (SOC) to predict parental adherence to preschooler's preventive dental visits. METHODS: Data regarding socio-economic demographics were collected from parents of children aged 2-6 years. Constructs of TPB including parental attitudes, subjective norms (SN), Perceived Behavioural Control (PBC), and intention to attend preventive dental visits for their preschoolers were collected by questionnaire, alongside parents' sense of coherence (SOC). Dental attendance was measured by asking if the child had a regular dental visit during the last year. Structural Equation Modeling Analysis (SEMA) was carried out to identify significant direct and indirect (mediated) pathways in the extended TPB model. RESULTS: Three hundred and seventy-eight mothers (mean age = 34.41 years, range 22-48) participated in the study. The mean age of children was 3.92 years, range: 2-6), and 75.9% had dental insurance. Results of the final model showed that predisposing factors (child's birthplace and mother's birthplace) significantly predicted enabling resources (family monthly income and child's dental insurance status); both predicted the TPB components (PBC, SN, and attitude). TPB components, in turn, predicted behavioural intention. However, contrary to expectation, intention did not significantly predict dental attendance in the past 12 months. Parent's SOC significantly predicted TPB components and dental attendance. Overall, 56% of the variance in dental attendance was explained by the expanded TPB model. CONCLUSIONS: The expanded TPB model explained a great deal of variance in preschooler's dental attendance. These findings suggest that the expanded model could be used as the framework for designing interventions or strategies to enhance dental attendance among preschoolers; in particular, such strategies should focus specifically on enhancing parental SOC including empowerment.

Clustering and Sampling of the c-Met Conformational Space: A Computational Drug Discovery Study.

BACKGROUND: c-Met kinase plays a critical role in a myriad of human cancers, and a massive scientific work was devoted to design more potent inhibitors. OBJECTIVE: In this study, 16 molecular dynamics simulations of different complexes of potent c-Met inhibitors with U-shaped binding mode were carried out regarding the dynamic ensembles to design novel potent inhibitors. METHODS: A cluster analysis was performed, and the most representative frame of each complex was subjected to the structure-based pharmacophore screening. The GOLD docking program investigated the interaction energy and pattern of output hits from the virtual screening. The most promising hits with the highest scoring values that showed critical interactions with c-Met were presented for ADME/Tox analysis. RESULTS: The screening yielded 45,324 hits that all of them were subjected to the docking studies and 10 of them with the highest-scoring values having diverse structures were presented for ADME/Tox analyses. CONCLUSION: The results indicated that all the hits shared critical Pi-Pi stacked and hydrogen bond interactions with Tyr1230 and Met1160 respectively.

Application of the Theory of Planned Behavior to Predict Dental Attendance and Caries Experience among Children of Newcomers.

Background: This study aimed to explore the predictors of regular dental attendance behavior and caries experience among children of newcomers to Canada using the Theory of Planned Behavior (TPB). Methods: A total of 274 newcomer parents with a child aged 1 to 12 years old who had lived in Canada for 10 years or less participated in this cross-sectional study. Children underwent a dental examination to measure their deft/DEFT, and parents completed a self-administered questionnaire. Parental attitudes, subjective norms, perceived behavioral control (PBC), and intention were examined using Structural Equation Modeling (SEM) as predictors of dental attendance behavior and caries experience using the TPB model. Results: Out of all the components of the model, attitude and PBC significantly predicted the intention (p < 0.05) while the subjective norm had no statistical effects on the loading of the model (p > 0.05). Intention significantly predicted behavior, but behavior could not predict caries experience. Although 51.6% of the variance of intention was predicted by this model, only 0.2% of the variance for dental attendance behavior was explained. Conclusions: The theory of planned behavior was successful in predicting dental attendance intention and behavior for children among newcomers, but this behavior could not predict caries experience in children.

Cementum regeneration using stem cells in the dog model: A systematic review.

OBJECTIVE: Restoring lost tissues of the periodontium, such as cementum, is essential in reducing the risk of tooth loss due to periodontitis and/or severe root resorption. Stem cell therapy is a regenerative strategy in cementum regeneration. This systematic review aimed to analyze the effect of various stem cells and their transplantation method on cementum regeneration in the dog model. METHODS: Electronic databases were searched, in addition to performing hand searches and a gray literature search. Titles and abstracts were searched according to the inclusion criteria and full texts were selected to be included in this systematic review. Data was extracted from each article and risk of bias was assessed for individual studies. RESULTS: Most studies reported that the treatment using a variety of stem cells resulted in significantly greater cementum regeneration. CONCLUSIONS: Because of variations in additional factors included in each study and varied risk of bias among those studies, the effect of each type of stem cell on cementum regeneration in dogs is difficult to clarify. Additional information needs to be obtained from each study in order to further analyze the individual effect of stem cells on cementum regeneration in dogs.

Parent's Sense of Coherence and Children's Oral Health-Related Behaviors: Is There an Association?

PURPOSE: Parental capacity to face day-to-day stressors has a relevant role in recognizing and mobilizing resources to control children's oral health behaviors. This capacity has been explored by means of the sense of coherence. The purpose of this study was to explore the association between mothers' sense of coherence (SOC) and their preschool children's oral health-related behaviors. METHODS: Mothers and their pre-school children were recruited during immunization programs at community health centers in Edmonton, Canada. Participants answered eight questions on socio-demographics (covariates), parents' SOC (main independent variable), and children's oral health-related practices (outcome variables). Statistical analyses comprised a two-sample t test, chi-square test, and logistic regression. RESULTS: A total of 378 pairs of mothers/ children participated in this study. Children's mean age was 3.92±(1.33) years. Mothers' SOC was statistically associated with children's frequency of sugar consumption and frequency and pattern of dental visits. The children of mothers who had higher levels of SOC presented a lower frequency intake of food or drink containing sugar and were more likely to visit the dentist for preventive purposes. CONCLUSIONS: Mothers' sense of coherence had a significant association with children's oral health-related behaviors; a higher SOC of mothers was associated with more positive behaviors among their children.

Associations among dental insurance, dental visits, and unmet needs of US children.

BACKGROUND: In this study, the authors explored the associations between dental visits and unmet dental needs of children on the basis of their insurance type in the United States. METHODS: The authors used the National Health Interview Surveys from 1997 through 2014 to collect data on dental visits, unmet dental needs, and type of insurance for children aged 2 to 17 years in the United States. Unmet dental need was based on not receiving needed dental care during the past year because of financial constraints. Insurance types reported were private, Medicaid or public, other, and uninsured. The authors performed Pearson correlation coefficient analyses and used descriptive summary statistics. RESULTS: The number of uninsured children decreased by 58% from 1997 through 2014 with a substantial shift from private to public insurance coverage. Regardless of type, dental insurance status was associated positively with the use of dental services and negatively associated with levels of unmet dental needs. Unmet needs in the public insurance group decreased consistently since 2009. There was a significant negative correlation (P < .05) between dental visits and unmet dental needs with respect to public insurance, whereas there was no significant correlation for private insurance. CONCLUSIONS: Dental insurance played a significant role in children's use of dental services and their level of unmet dental needs. PRACTICAL IMPLICATIONS: The shift toward the use of public insurance along with a significant association between unmet needs and dental visits support the effectiveness of publicly funded programs in facilitating the use of dental services in the United States.

Predictors of postretention stability of mandibular dental arch dimensions in patients treated with a lip bumper during mixed dentition followed by fixed appliances.

OBJECTIVE: To identify which dental and/or cephalometric variables were predictors of postretention mandibular dental arch stability in patients who underwent treatment with transpalatal arch and lip bumper during mixed dentition followed by full fixed appliances in the permanent dentition. MATERIALS AND METHODS: Thirty-one patients were divided into stable and relapse groups based on the postretention presence or absence of relapse. Intercuspid, interpremolar, and intermolar widths; arch length and perimeter; crowding; and lower incisor proclination were evaluated before treatment (T0), after lip bumper treatment (T1), after fixed appliance treatment (T2), and a minimum of 3 years after removal of the full fixed appliance (T3). Logistic regression analyses were performed to evaluate the effect of changes between T0 and T1, as predictive variables, on the occurrence of relapse at T3. RESULTS: The model explained 53.5 % of the variance in treatment stability and correctly classified 80.6 % of the sample. Of the seven prediction variables, intermolar and interpremolar changes between T0 and T1 (P = .024 and P = .034, respectively) were statistically significant. For every millimeter of increase in intermolar and interpremolar widths there was a 1.52 and 2.70 times increase, respectively, in the odds of having stability. There was also weak evidence for the effect of sex (P = .047). CONCLUSIONS: The best predictors of an average 4-year postretention mandibular dental arch stability after treatment with a lip bumper followed by full fixed appliances were intermolar and interpremolar width increases during lip bumper therapy. The amount of relapse in this crowding could be considered clinically irrelevant.

Short- and long-term evaluation of mandibular dental arch dimensional changes in patients treated with a lip bumper during mixed dentition followed by fixed appliances.

OBJECTIVE: To evaluate short- and long-term mandibular dental arch changes in patients treated with a lip bumper during the mixed dentition followed by fixed appliances, compared with a matched control sample. MATERIALS AND METHODS: Dental casts and lateral cephalograms obtained from 31 consecutively treated patients before (T0) and after (T1) lip bumper, after fixed appliances (T2), and a minimum of 3 years after fixed appliances (T3) were analyzed. The control group was matched as closely as possible. Arch width, arch perimeter, arch length, and incisor proclination were evaluated. Repeated measures ANOVA was used to analyze changes in measurements over all four time points between treatment and control groups. RESULTS: Arch widths and crowding were always significantly different except at T2-T1. At T1-T0, only crowding decreased 3.2 mm while intercanine, interpremolar, and intermolar widths increased by 3.8, 3.3, and 3.9 mm, respectively. Changes at T3-T2 showed a significant decrease of 2.1 mm for crowding and an increase of 3.5, 2.9, 2.7, and 0.8 mm for intercanine, interpremolar, and intermolar widths and arch perimeter, respectively. Finally, at T3-T0, the reduction in crowding of 5.03 mm was significant and clinically important in the treated group. The differences between intercanine, interpremolar, and intermolar widths were also significant (2.1, 3.8, and 3.6 mm, respectively). All those differences favored the treated group. CONCLUSIONS: Mandibular dental arch dimensions were significantly changed after lip bumper treatment. At follow-up, all arch widths were slightly decreased, generating an increase of 0.4 mm in crowding, considered clinically irrelevant. Overall changes remained stable after an average 6.3-year follow-up.

Factors associated with the development of dental caries in children and adolescents in studies employing the life course approach: a systematic review.

The purpose of this article was to conduct a systematic review of studies that used the life course approach to evaluate the association between factors experienced in early life and throughout the lifetime and the development of dental caries in children and adolescents. A systematic search of five electronic databases was carried out. Hand searches of the reference lists of the included articles and a gray literature search were also performed. Quantitative studies that adopted the life course approach to examine the factors associated with the development of dental caries in children and adolescents were selected. Abstracts were screened by two reviewers. Reports with relevant abstracts received full-text review and were examined for inclusion in the present systematic review. Qualitative evaluation of the included articles was carried out using the Newcastle-Ottawa Scale. As a result of the high degree of heterogeneity, meta-analysis was not feasible. Among the 48 articles submitted to full-text analysis, 11 were included in the present systematic review. Different life course factors were associated with the development of dental caries among children and adolescents, including sociodemographic, biological, psychological, and oral health behaviors, as well as the dental status of mothers, children, and adolescents.

Impact of Sense of Coherence on Oral Health Behaviors: A Systematic Review.

OBJECTIVES: The aim of this review was to critically analyze the empirical evidence on the association between Sense of Coherence (SOC) and oral health behaviors through a systematic approach. METHODS: A systematic search up to April 2015 was carried out using the following electronic bibliographic databases: PubMed, Ovid MEDLINE; ISI Web of Science; and Ovid PsychInfo. Studies were included if they evaluated the relationship between SOC and oral health behaviors including tooth cleaning, fluoride usage, dietary habits, dental attendance, and smoking. We excluded studies that only assessed the relationship between oral health status and SOC without evaluating oral health behaviors. The New Castle Ottawa (NOS) quality assessment checklist was employed to evaluate the methodological quality of included studies. RESULTS: Thirty-nine potential papers met the preliminary selection criteria and following a full-text review, 9 papers were finally selected for this systematic review. Results provided by the included studies indicated different levels of association between SOC and oral health behaviors. The most frequent behaviors investigated were tooth brushing and dental attendance pattern. The impact of SOC on performing positive oral health behaviors, to some extent, was related to demographic and socio-economic factors. In addition, mothers' SOC influenced children's oral health practices. CONCLUSIONS: A more favorable oral health behavior was observed among those with a stronger SOC suggesting that the SOC can be a determinant of oral health-related behaviors including tooth brushing frequency, daily smoking, and dental attendance.

Predictors of long-term stability of maxillary dental arch dimensions in patients treated with a transpalatal arch followed by fixed appliances.

BACKGROUND: The aim of this retrospective study was to identify which dental and/or cephalometric variables were predictors of long-term maxillary dental arch stability in patients treated with a transpalatal arch (TPA) during the mixed dentition phase followed by full fixed appliances in the permanent dentition. METHODS: Thirty-six patients, treated with TPA followed up by full fixed appliances, were divided into stable and relapse groups based on the long-term presence or not of relapse. Intercuspid, interpremolar and intermolar widths, arch length and perimeter, crowding, and upper incisor proclination were evaluated before treatment (T 0), post-TPA treatment (T 1), post-fixed appliance treatment (T 2), and a minimum of 3 years after full fixed appliances' removal (T 3). A binary logistic regression was performed thereafter to evaluate the impact of the dental arch and cephalometric measurements at T 1 and the changes between T 0 and T 1 as predictive variables for relapse at T 3. RESULTS: The proposed model explained 42.7 % of the variance in treatment stability and correctly classified 72.2 % of the sample. Of the seven predictive variables, only upper anterior crowding (p = 0.029) was statistically significant. For every millimeter of decreased crowding at T 1 (after TPA treatment/before starting the fixed orthodontic treatment), there was an increase of 3.57 times in the odds of having stability. CONCLUSIONS: The best predictor of relapse was maxillary crowding before treatment. The odds of relapse increase by 3.6 times for every millimeter of crowding at baseline.

A study on quantitative structure-activity relationship and molecular docking of metalloproteinase inhibitors based on L-tyrosine scaffold.

BACKGROUND: MMP-2 enzyme is a kind of matrix metalloproteinases that digests the denatured collagens and gelatins. It is highly involved in the process of tumor invasion and has been considered as a promising target for cancer therapy. The structural requirements of an MMP-2 inhibitor are: (1) a functional group that binds the zinc ion, and (2) a functional group which interacts with the enzyme backbone and the side chains which undergo effective interactions with the enzyme subsites. METHODS: In the present study, a QSAR model was generated to screen new inhibitors of MMP-2 based on L-hydroxy tyrosine scaffold. Descriptors generation were done by Hyperchem 8, DRAGON and Gaussian98W programs. SPSS and MATLAB programs have been used for multiple linear regression (MLR) and genetic algorithm partial least squares (GA-PLS) analyses and for theoretical validation. Applicability domain of the model was performed to screen new compounds. The binding site potential of all inhibitors was verified by structure-based docking according to their binding energy and then the best inhibitors were selected. RESULTS: The best QSAR models in MLR and GA-PLS were reported, with the square correlation coefficient for leave-one-out cross-validation (Q(2) LOO) larger than 0.921 and 0.900 respectively. The created MLR and GA-PLS models indicated the importance of molecular size, degree of branching, flexibility, shape, three-dimensional coordination of different atoms in a molecule in inhibitory activities against MMP-2. The docking study indicated that lipophilic and hydrogen bonding interactions among the inhibitors and the receptor are involved in a ligand-receptor interaction. The oxygen of carbonyl and sulfonyl groups is important for hydrogen bonds of ligand with Leu82 and Ala83. R2 and R3 substituents play a main role in hydrogen bonding interactions. R1 is sited in the hydrophobic pocket. Methylene group can help a ligand to be fitted in the lipophilic pocket, so two methylene groups are better than one. The Phenyl group can create a π-π interaction with Phe86. CONCLUSIONS: The QSAR and docking analyses demonstrated to be helpful tools in the prediction of anti-cancer activities and a guide to the synthesis of new metalloproteinase inhibitors based on L-tyrosine scaffold.

The effect of pH on solubility of nano-modified endodontic cements.

AIMS: To evaluate the effect of storage pH on solubility of white mineral trioxide aggregate (WMTA), bioaggregate (BA), and nano WMTA cements. MATERIALS AND METHODS: Forty-eight moulds randomly allocated into three groups of pH 4.4 (group A), 7.4 (group B), and 10.4 (group C); and one empty as control in each group. Each group was further divided into three subgroups according to the material studied; WMTA, BA, and nano WMTA. The specimens in subgroup A were soaked in butyric acid buffered with synthetic tissue fluid (STF) (pH 4.4), while the samples in subgroups B (pH 7.4) and C (pH 10.4) buffered in potassium hydroxide for 24 h and then the loss of cement was determined. A two-way analysis of variance (ANOVA) and Tukey post-hoc statistical tests were used to detect any statistically significant differences among the groups/subgroups. RESULTS: Statistical analysis has showed the highest solubility in acidic pH for all tested materials. Nano WMTA samples in pH = 10.4 had the lowest and BA samples in pH = 4.4 showed the highest cement loss. CONCLUSION: The solubility of all tested cements can be jeopardized in acidic environment which might affect on their sealing characteristic in clinical scenario. However, nano WMTA cement due to its small size particles and different additives was capable of producing lower porosity in set material, which resulted in showing more resistance in acidic environment.

Mechanical response of dental cements as determined by nanoindentation and scanning electron microscopy.

This study evaluated the effects of nanoindentation on the surface of white mineral trioxide aggregate (WMTA), Bioaggregate and Nano WMTA cements. Cements were mixed according to the manufacturer directions, condensed inside glass tubes, and randomly divided into three groups (n = 8). Specimens were soaked in synthetic tissue fluid (pH = 7.4) and incubated for 3 days. Cement pellets were subjected to nanoindentation tests and observed by scanning electron microscopy. Then, the images were processed and the number of cracks and total surface area of defects on the surface were calculated and analyzed using ImageJ. Data were submitted to one-way analysis of variance and a post hoc Tukey's test. The lowest number of cracks and total surface of defects were detected in Nano WMTA samples; however, it was not significantly different from WMTA samples (p = 0.588), while the highest values were noticed in Bioaggregate specimens that were significantly different from Nano WMTA and WMTA (p = 0.0001). The surface of WMTA and Nano WMTA showed more resistance after exposure to nano-compressive forces which indicated a better surface tolerance against these forces and crack formation. This suggests these substances are more tolerant cement materials which can predictably withstand loaded situations in a clinical scenario.

A segmented principal component analysis--regression approach to QSAR study of peptides.

We employed segmented principal component analysis and regression, as a new methodology in quantitative structure-activity relationship (QSAR), to define new amino acid indices. The descriptors are first classified into different groups (based on the similarity in the information contents they are possessing) and then each group is subjected to principal component analysis (PCA), separately. The extracted principal components (PC) from the descriptor data matrix of each group can be considered as new sources of amino acid indices. These indices were used as input variables for QSAR study of two dipeptide data sets (58 angiotensin-converting enzyme (ACE) inhibitor activity, and 48 bitter tasting threshold (BTT) activity). Modeling between the indices and biological activity was achieved utilizing segmented principal component regression (SPCR) and segmented partial least squares (SPLS) methods. Both methods resulted in reliable QSAR models. In comparison with conventional principal component regression (PCR) and partial least square (PLS), the segmented ones produced more predictive models. In addition, the developed models showed better performances with respect to the previously reported models for the same data sets. It can be concluded that by segmentation of variables and partitioning of the information into informative and redundant parts, it is possible to discard the redundant part of variables and to obtain more appropriate models.