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The chronological age estimation of living individuals is a crucial part of forensic practice and clinical practice, such as in orthodontic treatment. It is well-known that methods for age estimation in living children should be tested on different populations. Ethnic affiliations in Brazil are divided into several major groups depending on the region, with the south of Brazil being known for its German immigration. (1) Background: This study aimed to evaluate the correlation between chronological age and dental age using Demirjian's method and Cameriere's method in a group of children from Joinville, South Brazil to investigate if both methods can be used to estimate dental age in this population. (2) Methods: The sample consisted of 229 panoramic radiographs (119 were males and were 110 females) from Brazilian children (ages ranging from 6 to 12 years). The chronological age at the time of the panoramic radiographic exam was calculated for each child. The dental age was estimated according to Demirjian's method and Cameriere's method. All continuous data were tested for normality by using the Shapiro-Wilk test. The Pearson correlation coefficient test was applied. An alpha of 5% ( p < 0.05) was used for all analyses. (3) Results: The mean chronological age was 8.75 years. According to Demirjian's method, the mean dental age was 9.3 years, while according to Cameriere's method, the mean dental age was 8.66 years. A strong correlation between chronological age and dental age according to Demirjian (r = 0.776 and p < 0.0001) and Cameriere (r = 0.735 and p < 0.0001) was observed for both genders. (4) Conclusions: Both methods presented a good correlation with chronological age in the studied population and could be used to assess dental age in this population.

Genetic polymorphisms could explain the inter-individual differences in the oral health-related quality of life (OHRQoL) of children with anterior open bite (AOB)., Objective: To assess the impact of AOB on OHRQoL in children and to evaluate whether MTR (rs1805087), MTRR (rs1801394), TGFβ1 (rs1800469) and TNF-α (rs1799964, rs1799724 and rs1800629) genes are potential biomarkers for OHRQoL in children with AOB., Study Design: A cross-sectional study was performed with 173 children aged between 2-6 years. The Brazilian version of Early Childhood Oral Health Impact Scale (ECOHIS) was applied. Genetic polymorphisms were analyzed using real-time PCR. Mann-Whitney U-test and Chi-square were used., Results: The overall mean ECOHIS scores were 5.49 (SD= 5.72) and 3.45 (SD = 4.49) (p < 0.01) in the AOB and control groups, respectively. Children with the CC genotype of TNF-α (rs1799724) had a significantly higher psychological QoL level. The MTRR AA genotype group showed a lower QoL level in the child subscale (p = 0.006), function (p = 0.017), and psychological (p = 0.006) domains. There was no significant difference between OHRQoL and the genetic polymorphisms in MTR and TGFβ1., Conclusions: Genetic polymorphisms in TNF-α and MTRR are associated with the impact on the OHRQoL in children with AOB.

Objectives: To explore the association between genetic polymorphisms in vitamin D receptor (VDR), vitamin D serum levels, and variability in dental age., Material and Methods: This cross-sectional study was based on an oral examination, panoramic radiograph analysis, and genotype analysis from biological samples. Dental age was evaluated using two different methods: Demirjian et al. (Hum Biol 45:211-227, 1973) and Hofmann et al. (J Orofac Orthop.78:97-111, 2017). The genetic polymorphisms BglI (rs739837) and FokI (rs2228570) in VDR were genotyped through real-time PCR. The vitamin D level was also measured in the serum. Delta (dental age-chronological age) was compared among genotypes in VDR in the co-dominant model. Multiple linear regression analysis was also performed. An established alpha of 5% was used., Results: Genotype distributions of BglI and FokI were not associated with dental maturity (p > 0.05). In the logistic regression analyses, genotypes in BglI and FokI and vitamin D levels were not associated with variability in dental age (p > 0.05)., Conclusions: The genetic polymorphisms BglI and FokI in VDR and the vitamin D levels were not associated with variability in dental age., Clinical Relevance: To unravel the factors involved in dental maturity can improve dental treatment planning in pediatric and orthodontic practice., (© 2021. The Author(s).)

The purpose of the study was to investigate the association between single nucleotide polymorphisms (SNPs) in genes encoding estrogen receptors (ESR1 and ESR2, respectively) and delayed tooth emergence (DTE). This cross-sectional study was composed of biological unrelated children of both sexes, age ranging from 11 to 13 years old. DTE was defined when the successor primary tooth was still present in the oral cavity after its exfoliation time or the absence of the permanent tooth emergence into the oral cavity. Children were diagnosed with DTE when they had at least one delayed permanent tooth, according to age of exfoliation of each tooth proposed by The American Dental Association. Genomic DNA from saliva was used to evaluate the SNPs in ESR1 (rs9340799 and rs2234693) and ESR2 (rs1256049 and rs4986938) using Real-Time PCR. Chi-square or Fisher exact tests and Logistic Regression adjusted by age and gender were performed. SNP-SNP interaction was accessed by multifactor dimensionality reduction (MDR) analysis also adjusted by gender and age. The established alpha of this study was 5%. Among 537 included children, 296 (55%) were in the "DTE" group and the 241 (45%) were in the "Control" group. Age and gender were not statistically different among the groups (p>0.05). Genotype distribution of the SNPs rs9340799, rs2234693, rs1256049 and rs4986938 were not associated with DTE (p> 0.05). The models elected by MDR were not statistically significant either. Conclusions: The studied SNPs in ESR1 and ESR2 were not associated with permanent DTE.

The CDK4/6 inhibitor, palbociclib (PAL), significantly improves progression-free survival in HR + /HER2 - breast cancer when combined with anti-hormonals. We sought to discover PAL resistance mechanisms in preclinical models and through analysis of clinical transcriptome specimens, which coalesced on induction of MYC oncogene and Cyclin E/CDK2 activity. We propose that targeting the G 1 kinases CDK2, CDK4, and CDK6 with a small-molecule overcomes resistance to CDK4/6 inhibition. We describe the pharmacodynamics and efficacy of PF-06873600 (PF3600), a pyridopyrimidine with potent inhibition of CDK2/4/6 activity and efficacy in multiple in vivo tumor models. Together with the clinical analysis, MYC activity predicts (PF3600) efficacy across multiple cell lineages. Finally, we find that CDK2/4/6 inhibition does not compromise tumor-specific immune checkpoint blockade responses in syngeneic models. We anticipate that (PF3600), currently in phase 1 clinical trials, offers a therapeutic option to cancer patients in whom CDK4/6 inhibition is insufficient to alter disease progression., Competing Interests: Declaration of interests All authors listed on this manuscript are/were paid employees and/or owned stock of Pfizer, Inc. during data collection, analysis, and interpretation of their contributions., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Control of the cell cycle through selective pharmacological inhibition of CDK4/6 has proven beneficial in the treatment of breast cancer. Extending this level of control to additional cell cycle CDK isoforms represents an opportunity to expand to additional tumor types and potentially provide benefits to patients that develop tumors resistant to selective CDK4/6 inhibitors. However, broad-spectrum CDK inhibitors have a long history of failure due to safety concerns. In this approach, we describe the use of structure-based drug design and Free-Wilson analysis to optimize a series of CDK2/4/6 inhibitors. Further, we detail the use of molecular dynamics simulations to provide insights into the basis for selectivity against CDK9. Based on overall potency, selectivity, and ADME profile, PF-06873600 ( 22 ) was identified as a candidate for the treatment of cancer and advanced to phase 1 clinical trials.

Objective: To investigate SNPs in bone- and cartilage-related genes and their interaction in the aetiology of sagittal and vertical skeletal malocclusions., Settings and Sample Population: This study included 143 patients and classified as follows: skeletal class I (n = 77), class II (n = 47) and class III (n = 19); maxillary retrusion (n = 39), protrusion (n = 52) and well-positioned maxilla (n = 52); mandibular retrognathism (n = 50), prognathism (n = 50) and well-positioned mandible (n = 43); normofacial (n = 72), dolichofacial (n = 55) and brachyfacial (n = 16)., Materials and Methods: Steiner's ANB, SNA, SNB angles and Ricketts' NBa-PtGn angle were measured to determine the skeletal malocclusion and the vertical pattern. Nine SNPs in BMP2, BMP4, SMAD6, RUNX2, WNT3A and WNT11 were genotyped. Chi-squared test was used to compare genotypes among the groups. Multifactor dimensionality reduction (MDR) and binary logistic regression analysis, both using gender and age as co-variables, were also used. We performed Bonferroni correction for multiple testing., Results: Significant associations at P < .05 were observed for SNPs rs1005464 (P = .042) and rs235768 (P = .021) in BMP2 with mandibular retrognathism and for rs59983488 (RUNX2) with maxillary protrusion (P = .04) as well as for rs708111 (WNT3A) with skeletal class III (P = .02; dominant model), rs1533767 (WNT11) with a brachyfacial skeletal pattern (P = .01, OR = 0.10; dominant model) and for rs3934908 (SMAD6) with prognathism (P = .02; recessive model). After the Bonferroni correction, none of the SNPs remained associated. The MDR predicted some interaction for skeletal class II, dolichofacial and brachyfacial phenotypes., Conclusion: Our results suggest that SNPs in BMP2, BMP4, SMAD6, RUNX2, WNT3A and WNT11 could be involved in the aetiology of sagittal and vertical malocclusions., (© 2020 The Authors. Orthodontics & Craniofacial Research published by John Wiley & Sons Ltd.)

Objective: The purpose of this study was to evaluate the correlation between the growth maturity indicators in orthodontic patients. Design : This cross-sectional study was performed on 37 orthodontic patients (17 males and 20 females). An anamnesis, clinical and image examination, and blood sample collection were performed. The inclusion criteria were non-syndromic Class II patients of both gender, age ranging between 10 to 16 years. The lateral cephalometric radiographs were evaluated using 6-stage cervical vertebrae maturation (CVM) technique. The hand-wrist radiographs were staged using the 11-stage skeletal maturation indicator (SMI) technique. Blood was collected in the same week of the images to quantify IGF-1 levels in serum. Data were tested for normality by Shapiro-Wilk test. The Pearson test was used to determine the correlation strength between the variables (alpha of 5%). Results : A strong correlation was observed only between SMI stages and CVM stages in the total sample (r=0.864; p<0.0001) and according to the gender (r=0.793; p<0.0001 for females; and r=0.753; p<0.0001 for males). IGF-1 was only moderately correlated with SMI stages and CVM stages. Conclusion : Hand-wrist and cervical vertebral stages were strongly correlated among them, however, IGF-1 was only moderately correlated with both skeletal maturity indicators., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Ankylosed teeth may have a significant esthetic and functional impact especially at the anterior segment of the upper arch. Treatment of ankylosed teeth is challenging. The objective of this case report is to describe a clinical case in which an ankylosed tooth was treated with the use of osteogenic distraction associated with simplified orthodontic biomechanics. A 17-year-old female Caucasian patient presented with a Class II malocclusion, severe maxillary dental crowding, moderate mandibular dental crowding, anterior open bite, upper midline deviation to the right, and upper right central incisor in infraocclusion due to ankylosis. Treatment involved the use of the ankylosed tooth as anchorage for the distalization of the right upper segment to correct the Class II malocclusion and to create space prior to surgery. After one week of surgical osteotomy, traction of the tooth and bone segment was initiated with the use of intermaxillary elastics. The ankylosed tooth was moved to the desired position. Bone formation and mucogingival tissue adaptation were observed. Thus, esthetic and functional improvement was achieved. Osteogenic distraction associated with simplified orthodontic biomechanics is an alternative to the treatment of ankylosed teeth which can replace the use of distractor screws, making treatment simpler and more accessible., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article.

Objectives: The aim of this study was to assess the quality of and outline the differences among recommendations of published clinical practice guidelines (CPGs) for the management of bisphosphonate-associated osteonecrosis of the jaw., Methods: We conducted a systematic literature search in PubMed, Cochrane, Embase, Web of Science, and Google web site. We selected CPGs supported by a nongovernmental organization or national institutes, related to bisphosphonate-associated osteonecrosis of the jaw in adults, in English language, and dated from January 2008 onward. The validity of each included CPG was appraised according to 2 validated appraisal tools for CPG that were independently used by 2 reviewers., Results: We identified 724 articles, of which 13 were included based on our eligibility criteria. Most CPGs were of good quality based on the appraisal tools for CPGs used in this study., Conclusion: We did not find consensus on all the recommendations of the evaluated CPGs. Thus, each clinical case must be assessed individually, considering the risks and benefits on the proposed dental treatment., (Copyright © 2017 Elsevier Inc. All rights reserved.)