The Complexity of Skeletal Transverse Dimension: From Diagnosis, Management, and Treatment Strategies to the Application of Collaborative Cross (CC) Mouse Model.

This study investigates the significance of skeletal transverse dimension (STD) in orthodontic therapy and its impact on occlusal relationships. The primary goal is to enhance understanding and promote the integration of transverse skeletal diagnostics into routine orthodontic assessments. To achieve this aim, the study employs a comprehensive approach, utilizing model analysis, clinical assessments, radiographic measurements, and occlusograms. The initial step involves a meticulous assessment of deficiencies in the maxilla, mainly focusing on transverse dimension issues. Various successful diagnostic methods are employed to ascertain the type and presence of these deficiencies. Furthermore, the study compares surgically assisted maxillary expansion (SARME) and orthopedic maxillary expansion (OME) in addressing skeletal transverse issues. Stability assessments and efficacy analyses are conducted to provide valuable insights into the superiority of SARME over OME. The findings reveal that proper evaluation of STD is crucial in orthodontic diagnosis, as overlooking transverse dimension issues can lead to complications such as increased masticatory muscle activity, occlusal interferences, and an elevated risk of gingival recession. Surgically assisted maxillary expansion emerges as a more stable solution than orthopedic methods. In conclusion, incorporating skeletal transverse diagnostics into routine orthodontic assessments is imperative for achieving optimal occlusal relationships and minimizing negative consequences on dentition, periodontium, and joints. The study emphasizes the significance of accurate three-dimensional assessments and recommends the consideration of SARME over OME for addressing skeletal transverse deficiencies. Finally, the Collaborative Cross (CC) mouse model is also a novel mouse model for studying complex traits. Exploring the Collaborative Cross mouse model opens avenues for future research, promising further insights into transverse skeletal issues in orthodontics.

Anterior Open Bite Malocclusion: From Clinical Treatment Strategies towards the Dissection of the Genetic Bases of the Disease Using Human and Collaborative Cross Mice Cohorts.

Anterior open bite malocclusion is a complex dental condition characterized by a lack of contact or overlap between the upper and lower front teeth. It can lead to difficulties with speech, chewing, and biting. Its etiology is multifactorial, involving a combination of genetic, environmental, and developmental factors. Genetic studies have identified specific genes and signaling pathways involved in jaw growth, tooth eruption, and dental occlusion that may contribute to open bite development. Understanding the genetic and epigenetic factors contributing to skeletal open bite is crucial for developing effective prevention and treatment strategies. A thorough manual search was undertaken along with searches on PubMed, Scopus, Science Direct, and Web of Science for relevant studies published before June 2022. RCTs (clinical trials) and subsequent observational studies comprised the included studies. Orthodontic treatment is the primary approach for managing open bites, often involving braces, clear aligners, or other orthodontic appliances. In addition to orthodontic interventions, adjuvant therapies such as speech therapy and/or physiotherapy may be necessary. In some cases, surgical interventions may be necessary to correct underlying skeletal issues. Advancements in technology, such as 3D printing and computer-assisted design and manufacturing, have improved treatment precision and efficiency. Genetic research using animal models, such as the Collaborative Cross mouse population, offers insights into the genetic components of open bite and potential therapeutic targets. Identifying the underlying genetic factors and understanding their mechanisms can lead to the development of more precise treatments and preventive strategies for open bite. Here, we propose to perform human research using mouse models to generate debatable results. We anticipate that a genome-wide association study (GWAS) search for significant genes and their modifiers, an epigenetics-wide association study (EWAS), RNA-seq analysis, the integration of GWAS and expression-quantitative trait loci (eQTL), and micro-, small-, and long noncoding RNA analysis in tissues associated with open bite in humans and mice will uncover novel genes and genetic factors influencing this phenotype.

Narrating the Genetic Landscape of Human Class I Occlusion: A Perspective-Infused Review.

This review examines a prevalent condition with multifaceted etiology encompassing genetic, environmental, and oral behavioral factors. It stands as a significant ailment impacting oral functionality, aesthetics, and quality of life. Longitudinal studies indicate that malocclusion in primary dentition may progress to permanent malocclusion. Recognizing and managing malocclusion in primary dentition is gaining prominence. The World Health Organization ranks malocclusions as the third most widespread oral health issue globally. Angle's classification system is widely used to categorize malocclusions, with Class I occlusion considered the norm. However, its prevalence varies across populations due to genetic and examination disparities. Genetic factors, including variants in genes like MSX1, PAX9, and AXIN2, have been associated with an increased risk of Class I occlusion. This review aims to provide a comprehensive overview of clinical strategies for managing Class I occlusion and consolidate genetic insights from both human and murine populations. Additionally, genomic relationships among craniofacial genes will be assessed in individuals with Class I occlusion, along with a murine model, shedding light on phenotype-genotype associations of clinical relevance. The prevalence of Class I occlusion, its impact, and treatment approaches will be discussed, emphasizing the importance of early intervention. Additionally, the role of RNA alterations in skeletal Class I occlusion will be explored, focusing on variations in expression or structure that influence craniofacial development. Mouse models will be highlighted as crucial tools for investigating mandible size and prognathism and conducting QTL analysis to gain deeper genetic insights. This review amalgamates cellular, molecular, and clinical trait data to unravel correlations between malocclusion and Class I phenotypes.

Comprehensive Deciphering the Complexity of the Deep Bite: Insight from Animal Model to Human Subjects.

Deep bite is a malocclusion phenotype, defined as the misalignment in the vertical dimension of teeth and jaws and characterized by excessive overlap of the upper front teeth over the lower front teeth. Numerous factors, including genetics, environmental factors, and behavioral ones, might contribute to deep bite. In this study, we discuss the current clinical treatment strategies for deep bite, summarize the already published findings of genetic analysis associated with this complex phenotype, and their constraints. Finally, we propose a comprehensive roadmap to facilitate investigations for determining the genetic bases of this complex phenotype development. Initially, human deep bite phenotype, genetics of human deep bite, the prevalence of human deep bite, diagnosis, and treatment of human deep bite were the search terms for published publications. Here, we discuss these findings and their limitations and our view on future strategies for studying the genetic bases of this complex phenotype. New preventative and treatment methods for this widespread dental issue can be developed with the help of an understanding of the genetic and epigenetic variables that influence malocclusion. Additionally, malocclusion treatment may benefit from technological developments like 3D printing and computer-aided design and manufacture (CAD/CAM). These technologies enable the development of personalized surgical and orthodontic guidelines, enhancing the accuracy and effectiveness of treatment. Overall, the most significant results for the patient can only be achieved with a customized treatment plan created by an experienced orthodontic professional. To design a plan that meets the patient's specific requirements and expectations, open communication between the patient and the orthodontist is essential. Here, we propose to conduct a genome-wide association study (GWAS), RNAseq analysis, integrating GWAS and expression quantitative trait loci (eQTL), micro and small RNA, and long noncoding RNA analysis in tissues associated with deep bite malocclusion in human, and complement it by the same approaches in the collaborative cross (CC) mouse model which offer a novel platform for identifying genetic factors as a cause of deep bite in mice, and subsequently can then be translated to humans. An additional direct outcome of this study is discovering novel genetic elements to advance our knowledge of how this malocclusion phenotype develops and open the venue for early identification of patients carrying the susceptible genetic factors so that we can offer early prevention and treatment strategies, a step towards applying a personalized medicine approach.

Skeletal Class II Malocclusion: From Clinical Treatment Strategies to the Roadmap in Identifying the Genetic Bases of Development in Humans with the Support of the Collaborative Cross Mouse Population.

Depending on how severe it is, malocclusion, which may involve misaligned teeth, jaws, or a combination of the two, can hurt a person's overall facial aesthetics. The maxillary molar develops before the mandibular molar in class II malocclusion, which affects 15% of the population in the United States. With a retrusive mandible, patients typically have a convex profile. The goal of this study is to classify the skeletal and dental variability present in class II malocclusion, to reduce heterogeneity, present the current clinical treatment strategies, to summarize the previously published findings of genetic analysis, discuss these findings and their constraints, and finally, propose a comprehensive roadmap to facilitate investigations aimed at determining the genetic bases of malocclusion development using a variety of genomic approaches. To further comprehend the hereditary components involved in the onset and progression of class II malocclusion, a novel animal model for class II malocclusion should be developed while considering the variety of the human population. To overcome the constraints of the previous studies, here, we propose to conduct novel research on humans with the support of mouse models to produce contentious findings. We believe that carrying out a genome-wide association study (GWAS) on a large human cohort to search for significant genes and their modifiers; an epigenetics-wide association study (EWAS); RNA-seq analysis; integrating GWAS and the expression of quantitative trait loci (eQTL); and the testing of microRNAs, small RNAs, and long noncoding RNAs in tissues related to the skeletal class II malocclusion (SCIIMO) phenotype, such as mandibular bone, gum, and jaw in humans and the collaborative cross (CC) mouse model, will identify novel genes and genetic factors affecting this phenotype. We anticipate discovering novel genetic elements to advance our knowledge of how this malocclusion phenotype develops and open the venue for the early identification of patients carrying the susceptible genetic factors so that we can offer early prevention treatment strategies.

Towards Genetic Dissection of Skeletal Class III Malocclusion: A Review of Genetic Variations Underlying the Phenotype in Humans and Future Directions.

INTRODUCTION: Skeletal abnormalities and malocclusions have varied features that impact populations globally, impairing aesthetics and lowering life quality. The prevalence of the Skeletal Class III disease is the lowest among all angle malocclusions, with varied prevalence across nations. Environmental, genetic, and societal factors play a role in its numerous etiologies. In this study, we conducted a thorough search across the published data relating to quantitative trait loci (QTL) and the genes associated with Class III progression in humans, discussed these findings and their limitations, and proposed future directions and strategies for studying this phenotype. METHODS: An inclusive search of published papers in the PubMed and Google Scholar search engines using the following terms: 1. Human skeletal Class III; 2. Genetics of Human skeletal Class III; 3. QTL mapping and gene associated with human skeletal Class III; 4. enriched skeletal Class-III-malocclusion-associated pathways. RESULTS: Our search has found 53 genes linked with skeletal Class III malocclusion reported in humans, genes associated with epigenetics and phenomena, and the top 20 enriched pathways associated with skeletal Class III malocclusion. CONCLUSIONS: The human investigations yielded some contentious conclusions. We conducted a genome-wide association study (GWAS), an epigenetics-wide association study (EWAS), RNA-seq analysis, integrating GWAS and expression quantitative trait loci (eQTL), micro- and small-RNA, and long non-coding RNA analysis in tissues connected to skeletal Class III malocclusion phenotype in tissues connected with the skeletal phenotype. Finally, we invite regional, national, and international orthodontists and surgeons to join this effort by contributing human samples with skeletal Class III malocclusion following the accepted Helsinki ethical protocol to challenge these phenomena jointly.

Intestinal cancer development in response to oral infection with high-fat diet-induced Type 2 diabetes (T2D) in collaborative cross mice under different host genetic background effects.

Type 2 diabetes (T2D) is a metabolic disease with an imbalance in blood glucose concentration. There are significant studies currently showing association between T2D and intestinal cancer developments. High-fat diet (HFD) plays part in the disease development of T2D, intestinal cancer and infectious diseases through many biological mechanisms, including but not limited to inflammation. Understanding the system genetics of the multimorbidity of these diseases will provide an important knowledge and platform for dissecting the complexity of these diseases. Furthermore, in this study we used some machine learning (ML) models to explore more aspects of diabetes mellitus. The ultimate aim of this project is to study the genetic factors, which underline T2D development, associated with intestinal cancer in response to a HFD consumption and oral coinfection, jointly or separately, on the same host genetic background. A cohort of 307 mice of eight different CC mouse lines in the four experimental groups was assessed. The mice were maintained on either HFD or chow diet (CHD) for 12-week period, while half of each dietary group was either coinfected with oral bacteria or uninfected. Host response to a glucose load and clearance was assessed using intraperitoneal glucose tolerance test (IPGTT) at two time points (weeks 6 and 12) during the experiment period and, subsequently, was translated to area under curve (AUC) values. At week 5 of the experiment, mice of group two and four were coinfected with Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn) strains, three times a week, while keeping the other uninfected mice as a control group. At week 12, mice were killed, small intestines and colon were extracted, and subsequently, the polyp counts were assessed; as well, the intestine lengths and size were measured. Our results have shown that there is a significant variation in polyp's number in different CC lines, with a spectrum between 2.5 and 12.8 total polyps on average. There was a significant correlation between area under curve (AUC) and intestine measurements, including polyp counts, length and size. In addition, our results have shown a significant sex effect on polyp development and glucose tolerance ability with males more susceptible to HFD than females by showing higher AUC in the glucose tolerance test. The ML results showed that classification with random forest could reach the highest accuracy when all the attributes were used. These results provide an excellent platform for proceeding toward understanding the nature of the genes involved in resistance and rate of development of intestinal cancer and T2D induced by HFD and oral coinfection. Once obtained, such data can be used to predict individual risk for developing these diseases and to establish the genetically based strategy for their prevention and treatment.

Intention of Mothers in Israel to Vaccinate their Sons against the Human Papilloma Virus.

PURPOSE: This study investigated the intention of mothers in Israel to vaccinate their sons against HPV, using the Health Belief Model (HBM) as a framework, while comparing between Arab and Jewish mothers. DESIGN AND METHODS: The study has a quantitative cross-sectional design. A convenience sample of 200 Jewish and Arab mothers of boys aged 5-18 completed a questionnaire based on the HBM. RESULTS: The research findings indicate that only 14% of the mothers, constituting mostly Arab mothers, vaccinated their sons against HPV. Moreover, mothers showed a moderate level of intention to vaccinate their sons. This level was similar among Arab and Jewish mothers. However, the health beliefs of Jewish and Arab mothers differed. The HBM was found to explain 68% of mothers' intention to vaccinate their sons against HPV, and the perceived benefits of the vaccine were the factor most affecting this intention. CONCLUSIONS: Although mothers' health beliefs concerning vaccinating their sons against HPV may vary between sectors, the HBM can be used to explain what motivates mothers to vaccinate their sons. PRACTICE IMPLICATIONS: The research findings can assist in designing a national project among mothers of boys aimed at raising HPV vaccination rates, in both the Jewish and the Arab sector.