Synthesis, biological evaluation and in silico studies of novel thiadiazole-hydrazone derivatives for carbonic anhydrase inhibitory and anticancer activities.

Thiadiazole and hydrazone derivatives (5a-5i) were synthesized and their chemical structures were verified and described by 1H NMR, 13C NMR, and HRMS spectra. Three cancer cell lines (MCF-7, MDA, and HT-29) and one healthy cell line (L929) were used to test the cytotoxicity activity of synthesized compounds as well as their inhibitory activity against carbonic anhydrase I, II and IX isoenzymes. Compound 5d (29.74 µM) had a high inhibitory effect on hCA I and compound 5b (23.18 µM) had a high inhibitory effect on hCA II. Furthermore, compound 5i was found to be the most potent against CA IX. Compounds 5a-5i, 5b and 5i showed the highest anticancer effect against MCF-7 cell line with an IC50 value of 9.19 and 23.50 µM, and compound 5d showed the highest anticancer effect against MDA cell line with an IC50 value of 10.43 µM. The presence of fluoro substituent in the o-position of the phenyl ring increases the effect on hCA II, while the methoxy group in the o-position of the phenyl ring increases the activity on hCA I as well as increase the anticancer activity. Cell death induction was evaluated by Annexin V assay and it was determined that these compounds cause cell death by apoptosis. Molecular docking was performed for compounds 5b and 5d to understand their biological interactions. The physical and ADME properties of compounds 5b and 5d were evaluated using SwissADME.

Shear bond strength of a self-adhering flowable composite when used for lingual retainer bonding.

OBJECTIVE: The goal of this work was to assess the shear bond strength (SBS) and fracture mode of a self-adhering flowable composite when used after thermocycling for lingual retainer bonding. MATERIALS AND METHODS: A total of 80 human mandibular incisor teeth were categorized into four equal groups: group 1: Vertise™ Flow (VF) without acid etching; group 2: VF with acid etching; group 3: VF with a self-etching bonding agent accompanied by an additional acid etching; group 4: Transbond LR control. Either VF or Transbond LR was applied to the lingual surface of the teeth by packing the material into cylindrical plastic matrices to simulate the lingual retainer bonding area. After all teeth were thermocycled (5000 cycles, 5 and 55 °C), fracture modes were examined under × 20 magnification. The SBS data were assessed via analysis of variance (ANOVA) and Tukey's tests. Fracture modes were analyzed by the χ(2) test at a significance level of 0.05. RESULTS: Statistically significant differences in SBS values between groups (p < 0.001) were observed. Group 4 exhibited the highest (14.63 ± 1.36 MPa) and group 1 the lowest SBS (2.67 ± 1.35 MPa) values. Statistically significant differences were noted in fracture modes between groups 1, 3, and 4 (p < 0.001). In all the self-adhering flowable composite groups, the adhesive type (tooth-composite interface) fracture occurred more frequently than cohesive and mixed-type fractures. CONCLUSION: When applied to bond lingual retainers to unetched enamel or with self-etching bonding agent accompanied by an additional acid etching, Vertise™ Flow resulted in a significant decrease in bond strength.

Graduate orthodontic education in Turkey: the residents' perspective.

The aim of the present study was to explore residents' perceptions of their educational and clinical treatment experiences including the number of clinical cases undertaken, patient completion rates, techniques utilised and the scientific component of Turkish graduate orthodontic programmes. Residents recorded in the list of Turkish Orthodontic Society were sent an e-mail to participate in a survey containing 46 multiple-choice questions and ten one-line answers. An e-mail with a personalised online link was sent to a total of 227 residents throughout the Turkey. Data were categorised, and basic statistics including chi-square comparative analyses were performed. A total of 136 (response rate of 59.91%) residents completed the survey. The majority of residents (58.08%) were either 'very satisfied' or 'satisfied' with their programme. Respondents said they have just the right amount of formal didactic teaching sessions or dedicated and protected academic time. Most residents (69.11%) indicated their programme offers training in numerous philosophies; whilst 97.79% said they have sufficient clinically based training and 42.64% said they have sufficient research-based training. Overall, residents in the Turkey are satisfied with their orthodontic programme. They receive comprehensive training with the opportunity to start and complete a significant number of their patients. The survey findings suggest that orthodontic programmes in Turkey are deficient in providing care to underserviced populations and disabled patients. Programmes could improve the opportunity for residents to treat patients requiring interdisciplinary treatment.

Aripiprazole in children and adolescents with conduct disorder: a single-center, open-label study.

OBJECTIVE: The aim of this study was to determine the eff ectiveness and safety of aripiprazole in children and adolescents with both attention deficit/hyperactivity disorder (ADHD) and conduct disorder (CD). METHODS: 20 children and adolescents, ranging in age from 6­16 years, participated in a singlecenter, open-label study (19 to completion). We began treating patients with 2.5 mg of aripiprazole in an open-label fashion for 8 weeks. Outcome measures included the Turgay DSM-IVbased child and adolescent behavior disorders screening and rating scale (T-DSM-IV), the clinical global impressions-severity and improvement scales (CGI-S and CGI-I), the child behavior checklist (CBCL), the teachers report form (TRF) and the extrapyramidal symptom rating scale (ESRS), along with laboratory assessments. RESULTS: The mean daily dosage of aripiprazole at the end of 8 weeks was 8.55 mg (SD = 1.73), with a maximum dosage of 10 mg. Based on the global improvement subscale of the CGI, we classified 12 of 19 patients (63.1 %) as responders (very much or much improved). We observed significant improvements after aripiprazole treatment with regard to inattention, hyperactivity/impulsivity, ODD, and CD subscales of the T-DSMIV (parent, teacher and clinician forms). We also observed significant improvements on many of the CBCL and TRF subscales (e. g., attention problems as well as delinquent and aggressive behavior). The participants tolerated aripiprazole, and no patient was excluded from the study because of adverse drug events. CONCLUSION: Aripiprazole is an eff ective and well-tolerated treatment for ADHD and CD symptoms; however, additional studies (specifically, placebo-controlled and double-blind studies) are needed to better defi ne the clinical use of aripiprazole in children and adolescents with ADHD-CD.

Effect of resveratrol on bone formation in the expanded inter-premaxillary suture: early bone changes.

OBJECTIVE: The aim of this study was to evaluate the effects of local resveratrol (RSVL) administration on bone formation in response to expansion of the inter-premaxillary suture, in rats. MATERIAL AND METHODS: Twenty 50- to 60-day-old male Wistar rats were separated into two equal groups. Both groups were subjected to expansion, and 30 cN of force was applied to the maxillary incisors with helical-spring. Twenty-four hours after appliance placement, single-dose 10 µmol/kg RSVL in the dimethylsulfoxide (DMSO) was injected to the inter-premaxillary suture in the experimental group. In the control group, the same amount of DMSO was injected to the suture of rats. Bone formation in the suture was evaluated histomorphometrically. The area of new bone (µm(2)), the perimeter around the new bone (µm), Feret's diameter (µm), the percentage of new bone to non-ossified tissue (%), and the number of osteoblast were measured and compared. Mann-Whitney U-test was used for statistical evaluation at p < 0.05 level. RESULTS: Statistically significant differences were found between the groups for all histomorphometric parameters. New bone area (p < 0.001), bone perimeter (p < 0.001), Feret's diameter (p < 0.001), percentage of new bone (p < 0.001), and the number of osteoblast (p < 0.001) were significantly larger in the experimental group when compared with the control. Bone histomorphometric measurements revealed that bone architecture in the RSVL treated rats was improved. CONCLUSIONS: Local application of RSVL during the early stages to orthopedically expanded inter-premaxillary suture area may stimulate bone formation and shorten the retention period, in rats.

Effect of modified and conventional facemask therapy on condylar position in Class III patients.

OBJECTIVES: To assess the effects of varying force direction of maxillary orthopedic protraction on mandibular condylar position. MATERIAL AND METHODS: The conventional facemask group (Group 1) comprised 22 patients, 11 girls, and 11 boys (mean age: 9.3 ± 1.3 years); the modified facemask group (Group 2) comprised 22 patients, 12 girls, and 10 boys (mean age: 9.4 ± 1.5 years); and the control group (Group 3) comprised 21 subjects, 11 girls, and 10 boys (mean age: 9.8 ± 1.9 years). Changes in mandibular position indicator (MPI ®) measurements of the SAM ® 3 articulator were evaluated. Treatment and control changes within groups and between groups were analyzed statistically. Intra-group comparisons were tested with the non-parametric Wilcoxon's test and inter-group changes with Kruskal-Wallis. The statistical significance of inter-group differences was further assessed with the Mann-Whitney test for independent samples with Bonferroni's correction. RESULTS: Antero-posterior positional changes of the left condyle were found higher in the controls than in Group 1 (p<0.016). Superior-inferior positional changes of the left condyle were also found significantly higher in controls than in Group 2 (p<0.016). No other significant changes in condylar position were determined in either group. In the treatment groups, asymmetrical condylar position diminished and became symmetrical with treatment in the antero-posterior direction (Group 1: 13.64%, Group 2: 36.37%) plane. In controls, the antero-posterior change of asymmetry was smaller (antero-posterior change: 7.60%). CONCLUSION: These findings generally suggest that modified and conventional facemask therapy with expansion had no adverse effects on the temporomandibular and masticatory system.

Effects of different topical agents on enamel demineralization around orthodontic brackets: an in vivo and in vitro study.

BACKGROUND: The aim of this study was to evaluate the in vivo and in vitro effects of a casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and fluoride containing topical agents in reducing enamel demineralization around orthodontic brackets, and to compare this with a control group. METHODS: Twenty-one patients and 60 extracted premolars were divided into three groups: two experimental and one control. Tooth Mousse® (CPP-ACP gel; GC-Corp, Tokyo, Japan) and Fluoridin N5® (Fluoride gel; Voco-GmbH, Cuxhaven, Germany) were applied to tooth surfaces around orthodontic brackets in the experimental groups. Teeth were extracted after 60 days to evaluate the in vivo effects of the testing materials. For the in vitro experiment, samples were cycled for 14 days through a daily procedure of demineralization. All teeth were sectioned and evaluated by superficial microhardness analysis. An indentation was made from two positions (occlusal-cervical) and one depth (10 µm). RESULTS: Comparisons of occlusal and cervical microhardness scores for all specimens showed no statistically significant side differences. A multiple comparison test showed that the use of CPP-ACP and fluoride containing topical gels were more significantly efficient than the control group (p<0.001). No significant differences were detected between CPP-ACP and the fluoride groups against demineralization. CONCLUSIONS: In vivo and in vitro evaluations indicated that CPP-ACP and fluoride containing agents successfully inhibited caries around orthodontic brackets.

In vivo effects of amorphous calcium phosphate-containing orthodontic composite on enamel demineralization around orthodontic brackets.

BACKGROUND: The aim of this study was to evaluate the in vivo effects of an amorphous calcium phosphate-containing orthodontic composite in reducing enamel demineralization around orthodontic brackets, and to compare it with the control. METHODS: Fourteen orthodontic patients were divided into two equal groups. They received brackets fitted to all first premolars, bonded with either Aegis Ortho® (The Bosworth Co.), an ACP-containing orthodontic composite (experimental group), or Concise® (3M Dental Products), a resin-based orthodontic composite (control group). After 30 days, the teeth were extracted and longitudinally sectioned, and evaluated by superficial-microhardness analysis. The determinations were made at the bracket edge cementing limits and at occlusal and cervical points 100 and 200 µm away from the edge. In all of these positions, indentations were made at depths of 10, 20, 30, 50, 70, and 90 µm from the enamel surface. Analysis of variance (ANOVA) and Tukey post hoc test was used. The statistical significance level was set at p<0.05. RESULTS: The ANOVA showed statistically significant differences for position, material, depth, and their interactions (p<0.001). The multiple comparison test showed that the ACP-containing orthodontic composite was significantly more efficient than the control composite, reducing enamel demineralization in almost all evaluations (p<0.001). CONCLUSIONS: Present results indicated that ACP-containing orthodontic composite for bonding orthodontic brackets successfully inhibited demineralization in vivo. This effect was localized to the area around the brackets and was statistically significant after 30 days.

Effect of periosteal stimulation therapy on bone formation in orthopedically expanded suture in rats.

OBJECTIVE: The aim of this experimental study was to evaluate the effects of periosteal stimulation therapy (PST), on bone regeneration in response to expansion of the interpremaxillary suture, in rats. MATERIAL AND METHODS: Sixteen male, 50-60 days old Wistar rats were divided into two equal groups (control and experimental). Both groups were subjected to expansion for 5 days, and 30 cN of force was applied to the maxillary incisors with helical spring. On the 2nd day of the expansion procedure in the experimental group, the periosteum over the interpremaxillary suture was stimulated locally by intraperiosteal penetrations with a hypodermic needle. Bone regeneration in the interpremaxillary suture was evaluated by bone histomorphometry and the new bone area, bone perimeter, feret's diameter and new bone/old bone percentage parameters were evaluated. Mann-Whitney U-test was used for statistical evaluation at p < 0.05 level. RESULTS: Significant differences were found between groups for all investigated histomorphometric parameters. New bone area (p < 0.01), bone perimeter (p < 0.05), feret's diameter (p < 0.01) and new bone/old bone percentage (p < 0.01) measurements were significantly higher in the experimental group than that in the control. Bone histomorphometric measurements revealed that bone architecture in the PST group was improved. CONCLUSIONS: Local stimulation of the periosteum of the sutural area during expansion stimulates bone formation and improves healing.

Microleakage between composite/wire and composite/enamel interfaces of flexible spiral wire retainers: direct versus indirect application methods.

OBJECTIVE: The aim of this in vitro study was to compare the microleakage of flexible spiral wire retainers (FSWR) at composite/wire and composite/enamel interfaces produced by an indirect application method to that of a conventional direct application method. MATERIALS AND METHODS: Forty freshly extracted human mandibular incisor teeth were randomly divided into two equal groups. Group 1 was bonded directly according to the manufacturer's recommendations. Group 2 consisted of 20 teeth bonded indirectly with Transbond LR as the adhesive and Sondhi Rapid Set A/B Primer (3M Unitek, Monrovia, CA, USA), a filled resin primer. After bonding, specimens were further sealed with nail varnish, stained with 0.5% basic fuchsine for 24 h, sectioned and examined under a stereomicroscope that measured microleakage at the composite/wire and composite/enamel interfaces from both mesial and distal margins. Statistical analyses were performed using Wilcoxon and Mann-Whitney U-tests with Bonferroni correction. RESULTS: Statistical comparisons indicated that no statistically significant differences were observed between composite/wire and composite/enamel interfaces for direct vs. indirect application procedures (Direct method p = 0.630 and Indirect method p = 0.930). Comparisons of the microleakage scores between direct and indirect FSWR application groups at composite/wire and composite/enamel interfaces indicated no statistically significant microleakage differences at mesial or distal margins (Composite/enamel interface p = 0.361 and Composite/wire interface p = 0.270). CONCLUSION: The type of FSWR application procedures (direct vs. indirect) did not significantly affect the amount of microleakage at the enamel/composite/wire complex.

Centaurea revisited: A molecular survey of the Jacea group.

BACKGROUND AND AIMS: The genus Centaurea has traditionally been considered to be a complicated taxon. No attempt at phylogenetic reconstruction has been made since recent revisions in circumscription, and previous reconstructions did not include a good representation of species. A new molecular survey is thus needed. METHODS: Phylogenetic analyses were conducted using sequences of the internal transcribed spacers (ITS) 1 and 2 and the 5.8S gene. Parsimony and Bayesian approaches were used. KEY RESULTS: A close correlation between geography and the phylogenetic tree based on ITS sequences was found in all the analyses, with three main groups being resolved: (1) comprising the most widely distributed circum-Mediterranean/Eurosiberian sections; (2) the western Mediterranean sections; and (3) the eastern Mediterranean and Irano-Turanian sections. The results show that the sectional classification in current use needs major revision, with many old sections being merged into larger ones. A large polytomy in the eastern Mediterranean clade suggests a rapid and recent speciation in this group. Some inconsistencies between morphology and molecular phylogeny may indicate that hybridization has played a major role in the evolution of the genus. CONCLUSIONS: Phylogenetic analysis of ITS has been useful in identifying the major lineages in the group, and unraveling many inconsistencies in the sectional classification. However, most recent groups in the eastern Mediterranean clade are not resolved and reticulation in the western Mediterranean group of sections makes phylogenetic relationships within these two groups somewhat obscure.

Extraperitoneal retention sutures.

A new technic for the application of retention sutures is described. Intestinal obstruction caused by the entrapped intestine between the retention suture and the abdominal wall is practically eradicated with this technic.