What we eat and how we eat it are critical to our health, well-being, and risk of developing a myriad of diseases. The importance of a healthy diet and disease control has long been recognized as an essential component of oral health care. Poor diet is not only a key contributor to oral health and disease, but it is now considered the leading cause of death in the United States, having overtaken the decades-long reign of tobacco as leader.1

The challenges facing dentistry in the United States in 2023 were diverse to say the least. As we enter that 25th year of the first century in a new millennium, the dental care profession and delivery of oral health care will undoubtedly face new challenges while managing those that followed us into the new quarter-century.

At the outset of the computer age, artificial intelligence (AI) quickly became a concept. John McCarthy, who coined the term at the Dartmouth Conference in 1956, defined AI as the science and engineering of making intelligent machines.1Homage to John McCarthy, the father of artificial intelligence (AI). Teneo.ai.https://www.teneo.ai/blog/homage-to-john-mccarthy-the-father-of-artificial-intelligence-aiDate accessed: August 25, 2023Google Scholar Fast-forward to the present and we are observing how AI is transforming the health care industry. In the past year, AI and its applications have received momentous news coverage in both the press and scientific literature. The proliferation of information and research on the topic is astounding. Searching PubMed on August 27, 2023, using the phrase “artificial intelligence 2023,” yielded a remarkable 23,457 articles. Adding “dentistry” to the search revealed 493 articles. In November 2022, the launch of ChatGPT (OpenAI), a generative large language AI model, created substantial interest in academia and the publishing world. A May 2023 JADA editorial on ChatGPT outlined the newest requirements and disclosures necessary when using generative AI for manuscript preparation.2Sardana D. Fagan T.R. Wright J.T. ChatGPT: a disruptive innovation or disrupting innovation in academia?.JADA. 2023; 154: 361-364Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar Although these forms of AI are capable of mining and evaluating massive data sets for information, the content created relies heavily on the input ChatGPT has available to it, which means users face the possibility of generating inaccurate text and responses. Still, certain commercially available tools, such as voice-recognition software, that enable electronic charting of dental examinations and the use of AI-generated patient notes on health status and therapeutic recommendations, have the potential to change the way we approach patient-centered care. The American Dental Association formed an expert panel that developed a white paper titled “Dentistry: Overview of Artificial Intelligence and Augmented Intelligence Uses in Dentistry” that was released in December 2022.3Dentistry: overview of artificial intelligence and augmented intelligence uses in dentistry. SCDI white paper no. 1106. American Dental Association.https://www.ada.org/-/media/project/ada-organization/ada/ada-org/files/resources/practice/dental-standards/ada_1106_2022.pdf?rev=6597958fb295462492935589971e27c3Date accessed: August 25, 2023Google Scholar The document included explanations of AI nomenclature and reviews of the types of data sets necessary to train and validate AI applications and algorithms. Although AI is not being used extensively in dentistry, the potential applications for oral health care are broad in scope, including marketing, filing claims, voice-activated dental charting, diagnostics, and treatment planning.Although artificial intelligence is not being used extensively in dentistry, the potential applications include marketing, filing claims, voice-activated dental charting, diagnostics, and treatment planning. Although artificial intelligence is not being used extensively in dentistry, the potential applications include marketing, filing claims, voice-activated dental charting, diagnostics, and treatment planning. Digital data are necessary for AI applications, and dental offices wanting to take advantage of potential AI uses in oral health care will benefit from having an electronic dental record (EDR) and digital imaging capabilities. Although more than 75% of dental practices use computer systems for patient appointments and billing and chairside internet access, and 65% of dental offices have digital radiography, only a little more than one-half of dental offices use EDRs.4Acharya A. Schroeder D. Schwei K. Chyou P.H. Update on electronic dental record and clinical computing adoption among dental practices in the United States.Clin Med Res. 2017; 15: 59-74Crossref PubMed Scopus (14) Google Scholar Patient data collected from the EDR, typically at the point of contact, can be evaluated using AI and used to provide clinical decision support (CDS) that helps providers make informed decisions.5Goodman K.E. Rodman A.M. Morgan D.J. Preparing physicians for the clinical algorithm era.N Engl J Med. 2023; 389: 483-487Crossref PubMed Scopus (1) Google Scholar Using AI in this manner has the potential to improve health care and the efficiency of care delivery, but carries with it certain risks (for example, confidentiality of patient information). Information from the EDR, including demographic characteristics, diet information, clinical examination and radiographic findings, and biological assessments, can be included in algorithms used to classify a patient’s level of disease, disease risk, and disease progression. Examples of these approaches include classifying children with early childhood caries. Using patient information derived from 1 study, the authors predicted which children would develop caries during a 3-month period; the highest area under the curve was 0.91 (95% CI, 0.87 to 0.94).6Qu X. Zhang C. Houser S.H. et al.Prediction model for early childhood caries risk based on behavioral determinants using a machine learning algorithm.Comput Methods Programs Biomed. 2022; 227107221https://doi.org/10.1016/j.cmpb.2022.107221Crossref PubMed Scopus (2) Google Scholar Some models diagnose gingivitis and classify periodontal disease using a variety of data inputs.7Patil S. Albogami S. Hosmani J. et al.Artificial intelligence in the diagnosis of oral diseases: applications and pitfalls.Diagnostics (Basel). 2022; 12: 1029https://doi.org/10.3390/diagnostics12051029Crossref PubMed Scopus (14) Google Scholar These types of predictive algorithms can help focus resources and therapeutic approaches to manage oral diseases. The evolution of CDS has been impressive and continuous. It is critical that clinicians understand how CDS systems work and their potential pitfalls.5Goodman K.E. Rodman A.M. Morgan D.J. Preparing physicians for the clinical algorithm era.N Engl J Med. 2023; 389: 483-487Crossref PubMed Scopus (1) Google Scholar Increasingly sophisticated CDS-developed algorithms have taken us beyond identifying a patient’s potential drug interactions and need for antibiotics or medical alerts to models that can identify data patterns for diagnostics and prognostication.6Qu X. Zhang C. Houser S.H. et al.Prediction model for early childhood caries risk based on behavioral determinants using a machine learning algorithm.Comput Methods Programs Biomed. 2022; 227107221https://doi.org/10.1016/j.cmpb.2022.107221Crossref PubMed Scopus (2) Google Scholar AI and CDS algorithms analyze data and generate prediction-based likelihoods and probabilities. In dentistry, these likelihoods might take the form of predicting the development or progression of a patient’s caries or periodontal disease. These algorithms can generate diagnostic probabilities, such as the likelihood of having a fractured tooth root, on the basis of radiographic findings. In endodontics, AI is being used to assist in diagnosing periapical lesions and locating apical foramen using a variety of imaging platforms, including cone-beam computed tomography. As the practice of dentistry continues to incorporate AI, clinicians will be called on increasingly to use these technologies and interpret the probabilistic information provided in their decision making.5Goodman K.E. Rodman A.M. Morgan D.J. Preparing physicians for the clinical algorithm era.N Engl J Med. 2023; 389: 483-487Crossref PubMed Scopus (1) Google Scholar How does the oral health care community prepare for what I believe is the inevitable incorporation of AI into mainstream practice? The US Food and Drug Administration is developing regulatory actions to help ensure that algorithms are safe and effective and has begun regulating some CDS algorithms as medical devices that require approval. Oral health care practitioners should understand the implications for obtaining probabilistic information from an algorithm and the uncertainties inherent in the approach. The probabilities are based on data sets that are hopefully large and highly accurate. However, each patient is unique. You never know all of the potential variables at play and predictions are not going to be 100% accurate. Preparing for the future with AI will require changes in our educational processes. Students and practitioners must be prepared to incorporate these innovative approaches into diagnosis, treatment planning, and outcome prediction, and they should understand it is ultimately the practitioner making the calls, even with the support of probabilistic data helping inform their decisions. It is hard to predict the future and how humans and machines will work together. As I wrap up this editorial, I cannot help but wonder whether using a generative AI program might have helped improve this piece. The possibilities associated with these AI technologies will change oral health care forever, but I am confident the human touch and the human mind will continue to be paramount to delivering the best patient care outcomes and experiences for the foreseeable future. Embracing these modern technologies will require work to understand the ramifications and operation of these diverse AI applications. Adopting these technologies will help ensure optimal patient care delivery and health outcomes. Dr. Wright is a professor, Division of Pediatric Dentistry and Public Health, Department of Pediatric Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, and the editor, The Journal of the American Dental Association.

Dental enamel is a specialized tissue that has adapted over millions of years of evolution to enhance the survival of a variety of species. In humans, enamel evolved to form the exterior protective layer for the crown of the exposed tooth crown. Its unique composition, structure, physical properties and attachment to the underlying dentin tissue allow it to be a resilient, although not self-repairing, tissue. The process of enamel formation, known as amelogenesis, involves epithelial-derived cells called ameloblasts that secrete a unique extracellular matrix that influences the structure of the mineralizing enamel crystallites. There are over 115 known genetic conditions affecting amelogenesis that are associated with enamel phenotypes characterized by either a reduction of enamel amount and or mineralization. Amelogenesis involves many processes that are sensitive to perturbation and can be altered by numerous environmental stressors. Genetics, epigenetics, and environment factors can influence enamel formation and play a role in resistance/risk for developmental defects and the complex disease, dental caries. Understanding why and how enamel is affected and the enamel phenotypes seen clinically support diagnostics, prognosis prediction, and the selection of treatment approaches that are appropriate for the specific tissue defects (e.g., deficient amount, decreased mineral, reduced insulation and hypersensitivity). The current level of knowledge regarding the heritable enamel defects is sufficient to develop a new classification system and consensus nosology that effectively communicate the mode of inheritance, molecular defect/pathway, and the functional aberration and resulting enamel phenotype.

AimBiallelic loss-of-function FAM20A mutations cause amelogenesis imperfecta (AI) type IG, better known as enamel renal syndrome (ERS), characterized by severe enamel hypoplasia, delayed/failed tooth eruption, intrapulpal calcifications, gingival hyperplasia and nephrocalcinosis. FAM20A binds to FAM20C, the Golgi casein kinase (GCK) and potentiates its function to phosphorylate secreted proteins critical for biomineralization. While many FAM20A pathogenic mutations have been reported, the pathogeneses of orodental anomalies in ERS remain to be elucidated. This study aimed to identify disease-causing mutations for patients with ERS phenotypes and to discern the molecular mechanism underlying ERS intrapulpal calcifications. MethodologyPhenotypic characterization and whole exome analyses were conducted for 8 families and 2 sporadic cases with hypoplastic AI. A minigene assay was performed to investigate the molecular consequences of a FAM20A splice-site variant. RNA sequencing followed by transcription profiling and gene ontology (GO) analyses were carried out for dental pulp tissues of ERS and the control. ResultsBiallelic FAM20A mutations were demonstrated for each affected individual, including 7 novel pathogenic variants: c.590-5T>A, c.625T>A (p.Cys209Ser), c.771del (p.Gln258Argfs*28), c.832_835delinsTGTCCGACGGTGTCCGACGGTGTC CA (p.Val278Cysfs*29), c.1232G>A (p.Arg411Gln), c.1297A>G (p.Arg433Gly) and c.1351del (p.Gln451Serfs*4). The c.590-5T>A splice-site mutation caused Exon 3 skipping, which resulted in an in-frame deletion of a unique region of the FAM20A protein, p.(Asp197_Ile214delinsVal). Analyses of differentially expressed genes in ERS pulp tissues demonstrated that genes involved in biomineralization, particularly dentinogenesis, were significantly upregulated, such as DSPP, MMP9, MMP20 and WNT10A. Enrichment analyses indicated overrepresentation of gene sets associated with BMP and SMAD signalling pathways. In contrast, GO terms related to inflammation and axon development were underrepresented. Among BMP signalling genes, BMP agonists GDF7, GDF15, BMP3, BMP8A, BMP8B, BMP4 and BMP6 were upregulated, while BMP antagonists GREM1, BMPER and VWC2 showed decreased expression in ERS dental pulp tissues. ConclusionsUpregulation of BMP signalling underlies intrapulpal calcifications in ERS. FAM20A plays an essential role in pulp tissue homeostasis and prevention of ectopic mineralization in soft tissues. This critical function probably depends upon MGP (matrix Gla protein), a potent mineralization inhibitor that must be properly phosphorylated by FAM20A-FAM20C kinase complex.

The importance of oral health and a functional dentition would seem to be evident. However, it also appears to be ignored or unnoticed from many standpoints. Evolutionarily, the dentition was critical to a person’s survival, serving as a tool, weapon, and means to acquire and consume nourishment. The demise of the dentition typically signaled the end of the life span, as being edentulous was incompatible with survival. As humans have transitioned to different diets and lifestyles, one might predict the importance of our dentition and oral health has diminished. But has it? There is no question that humans have been able to adapt and survive tooth loss and even complete edentulism better than hominids could a million years ago.1Lordkipanidze D. Vekua A. Ferring R. et al.The earliest toothless hominin skull.Nature. 2005; 4347034: 717-718Crossref Scopus (156) Google Scholar Although edentulism in the United States has declined substantially over the last 5 decades, it remains relatively high in adults 50 years or older (10%), particularly among those with chronic health problems.2Parker M.L. Thornton-Evans G. Wei L. Griffin S.O. Prevalence of and changes in tooth loss among adults aged ≥50 years with selected chronic conditions: United States, 1999-2004 and 2011-2016.MMWR Morb Mortal Wkly Rep. 2020; 69: 641-646Crossref PubMed Google Scholar,3Al-Zahrani M.S. Alhassani A.A. Melis M. Zawawi K.H. Depression is related to edentulism and lack of functional dentition: an analysis of NHANES data, 2005-2016.J Public Health Dent. 2021; 81: 206-213Crossref PubMed Scopus (2) Google Scholar We know that oral health goes well beyond just a healthy dentition to include having well-developed and healthy oral and craniofacial tissues and structures. It is not surprising that many studies inform us of the important relationships of oral and systemic health. For example, the impact of being edentulous on overall health is well-documented and involves multiple dimensions, such as nutritional status, mental health, and lifespan longevity.2Parker M.L. Thornton-Evans G. Wei L. Griffin S.O. Prevalence of and changes in tooth loss among adults aged ≥50 years with selected chronic conditions: United States, 1999-2004 and 2011-2016.MMWR Morb Mortal Wkly Rep. 2020; 69: 641-646Crossref PubMed Google Scholar, 3Al-Zahrani M.S. Alhassani A.A. Melis M. Zawawi K.H. Depression is related to edentulism and lack of functional dentition: an analysis of NHANES data, 2005-2016.J Public Health Dent. 2021; 81: 206-213Crossref PubMed Scopus (2) Google Scholar, 4Friedman P.K. Lamster I.B. Tooth loss as a predictor of shortened longevity: exploring the hypothesis.Periodontol 2000. 2016; 72: 142-152Crossref PubMed Scopus (47) Google Scholar We also know that tooth retention, particularly retaining 21 or more teeth (a functional dentition), is strongly associated with quality of life and well-being, and this important oral health metric has been improving.5Dye B.A. Weatherspoon D.J. Lopez Mitnik G. Tooth loss among older adults according to poverty status in the United States from 1999 through 2004 and 2009 through 2014.JADA. 2019; 150: 9-23.e3Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar Having good oral health is complex and multifactorial, so it is not surprising that challenges persist in improving oral health for all. Common oral conditions remain endemic in the population despite our advancing knowledge as to their pathogenesis and treatment. So, how has oral health faired over the past several decades? In 2000 as we entered the 21st century, then surgeon general David Satcher, MD, PhD, produced the 2000 Surgeon General’s Report on Oral Health in America that had an overarching message that you do not have good health if you do not have good oral health.62000 surgeon general’s report on oral health in America.https://www.nidcr.nih.gov/research/data-statistics/surgeon-generalDate accessed: January 7, 2022Google Scholar The report helped emphasize that oral health goes well beyond a healthy dentition and that good oral health adds value to peoples’ lives. Marked disparities in oral health were noted between population groups in the United States based on sex, income, age, and race or ethnicity.62000 surgeon general’s report on oral health in America.https://www.nidcr.nih.gov/research/data-statistics/surgeon-generalDate accessed: January 7, 2022Google Scholar It was predicted in the report that the national dental care cost would exceed $60 billion in 2000.62000 surgeon general’s report on oral health in America.https://www.nidcr.nih.gov/research/data-statistics/surgeon-generalDate accessed: January 7, 2022Google Scholar Two decades later the cost of oral health care has more than doubled to over $140 billion, but it remains a small percentage of the overall health care cost in the United States.7Solana K. HPI: dental spending decreased in 2020—pandemic-related government relief program spending was $8.7 billion in 2020. ADA News. December 30, 2021. Accessed January 11, 2022. https://www.ada.org/publications/ada-news/2021/december/hpi-dental-spending-decreased-in-2020Google Scholar In 2017, Dr. Satcher published an update on the surgeon general’s oral health report noting that marked disparities in oral health status, although improved in some areas, continued to exist.8Satcher D. Nottingham J.H. Revisiting oral health in America: a report of the surgeon general.Am J Public Health. 2017; 107: S32-S33Crossref PubMed Scopus (33) Google Scholar One noted success was improvements addressing access to dental care facilitated by the Patient Protection and Affordable Care Act, which defined dental care for children as an essential health benefit.8Satcher D. Nottingham J.H. Revisiting oral health in America: a report of the surgeon general.Am J Public Health. 2017; 107: S32-S33Crossref PubMed Scopus (33) Google Scholar In December 2021, the National Institutes of Health released a much-anticipated follow-up to the 2000 surgeon general’s report on oral health.9Oral health America: advances and challenges—executive summary. US Department of Health and Human Services, National Institutes of Health, National Institute of Dental and Craniofacial Research, 2021https://www.ncbi.nlm.nih.gov/books/NBK576536/Date accessed: January 7, 2022Google Scholar Originally commissioned by then US Surgeon General Jerome M. Adams, MD, MPH, this new report, titled “Oral Health in America: Advances and Challenges” is now available at the National Institute of Dental and Craniofacial Research’s website. This report, which is a culmination of years of work by hundreds of project participants, provides a comprehensive review of oral health since 2000. The 6 sections of the report detail what we have learned, advances that have been made, areas that remain a challenge, and the work still needing to be done. Although advances in the prevention and management of caries have resulted in some caries prevalence decrease for a few groups, not all have benefited. Millions of people in the United States remain affected by periodontal disease, with older adults being more likely to be affected.9Oral health America: advances and challenges—executive summary. US Department of Health and Human Services, National Institutes of Health, National Institute of Dental and Craniofacial Research, 2021https://www.ncbi.nlm.nih.gov/books/NBK576536/Date accessed: January 7, 2022Google Scholar Yet, older adults are twice as likely as adults younger than 65 years to have a dental implant, and the prevalence has increased a staggering 500% since the first report on oral health was released in 2000, raising concerns for increasing perimplantitis in ageing people in the United States.9Oral health America: advances and challenges—executive summary. US Department of Health and Human Services, National Institutes of Health, National Institute of Dental and Craniofacial Research, 2021https://www.ncbi.nlm.nih.gov/books/NBK576536/Date accessed: January 7, 2022Google Scholar Our understanding of the etiopathology of both caries and periodontal disease has advanced, and this new knowledge provides the foundation for future improvements in effective disease management. The report details how new knowledge related to human papillomavirus and cancer are advancing health care with the development of protective vaccines. The report further presents new health care concerns such as electronic cigarettes that have changed the oral health care landscape since 2000. The 2021 report reflects on 20 years of research strengthening our understanding on how social determinants of health have a profound impact on oral health outcomes and how we continue to be challenged with oral health disparities resulting from racial or ethnic and economic factors. The financing of dental care remains markedly different from medical care, with a substantial portion of dental care being financed out of pocket by the patient.9Oral health America: advances and challenges—executive summary. US Department of Health and Human Services, National Institutes of Health, National Institute of Dental and Craniofacial Research, 2021https://www.ncbi.nlm.nih.gov/books/NBK576536/Date accessed: January 7, 2022Google Scholar The 2 surgeon generals’ reports on oral health, spanning 2 decades, have helped increase the visibility of oral health issues and have created awareness for the public, policy makers, health care providers, and health care payers about the importance and value of oral health. With this information as a backdrop, what actions should society take to help improve the oral health of all people in the United States? What resources are we willing to commit to ensure that future reviews show continued and hopefully more substantial improvements in oral health? Unfortunately, oral health care is still not considered an essential health benefit for all segments of the population in the United States. Debates as to how best to provide oral health care to adults continues to be controversial. Many adults are deferring oral health care owing to cost.10Williams S. Wei L. Griffin S.O. Thornton-Evans G. Untreated caries among US working-aged adults and association with reporting need for oral health care.JADA. 2021; 152: 55-64Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar Proposals to include a dental benefit Medicare were met with mixed support and ultimately not included in the Biden administration’s Build Back Better infrastructure bill.11Garvin J. Medicare dental benefit not included in House of Representatives-passed legislation. ADA News. November 19, 2021. Accessed January 18, 2022. https://www.ada.org/publications/ada-news/2021/november/medicare-dental-benefit-not-included-in-house-passed-legislationGoogle Scholar Many remain opposed to government-supported health care or entitlements that bring us closer to universal dental coverage. The significant improvements in the oral health of children, as noted in the 2021 report, indicates that expanding access to dental care and bringing a population to near universal coverage does make a difference.9Oral health America: advances and challenges—executive summary. US Department of Health and Human Services, National Institutes of Health, National Institute of Dental and Craniofacial Research, 2021https://www.ncbi.nlm.nih.gov/books/NBK576536/Date accessed: January 7, 2022Google Scholar What are the best approaches for improving the oral health of our people and our communities is a hard and challenging question. As the 2021 report states, the United States is ageing, and older adults are retaining more teeth; yet disparities in tooth retention are increasing, creating conditions for much larger challenges to overcome if they are not addressed.9Oral health America: advances and challenges—executive summary. US Department of Health and Human Services, National Institutes of Health, National Institute of Dental and Craniofacial Research, 2021https://www.ncbi.nlm.nih.gov/books/NBK576536/Date accessed: January 7, 2022Google Scholar There will no doubt be multiple proposals and complex solutions. Making a difference over the next decade will require funding for oral health research and resources for care, especially for those at high risk for disease, the vulnerable and underserved.What are the best approaches for improving the oral health of our people and our communities is a hard and challenging questionMaking a difference over the next decade will require funding for oral health research and resources for care, especially for those at high risk for disease, the vulnerable and underserved. What are the best approaches for improving the oral health of our people and our communities is a hard and challenging question Making a difference over the next decade will require funding for oral health research and resources for care, especially for those at high risk for disease, the vulnerable and underserved. As the 2021 report expressed, we have made progress but there is clearly much more that needs to be done. Let us begin by investing additional resources into preventing and managing oral diseases, finding ways to make dental care an essential health benefit for all, and promoting oral health for a healthier nation.

STATEMENT OF PROBLEM:Advertisements of glass-ionomer-containing restorative materials recommend suitability as load-bearing permanent or semi-permanent restorations. Historically, unacceptably high wear rates limit clinical indications of glass-ionomer-containing restorations in this regard.OBJECTIVE:To compare the in vitro wear of contemporary glass-ionomer-containing dental materials commercially advertised for use in permanent dentition as load-bearing restorations in a chewing simulator. Resin composite was tested as a control.METHODS AND MATERIALS:A resin-modified glass ionomer (Ionolux, VOCO gmbH), a high viscosity glass-ionomer hybrid system (Equia Forte HT with Equia Coat, GC America), and a bioactive ionic resin with reactive glass filler (Activa Bioactive Restorative, Pulpdent) were evaluated. Filtek Supreme Ultra (3M ESPE) is a visible light-activated resin composite that served as a control. Standardized flat disk-shaped specimens (n=12/group) were submitted to 500,000 cycles with continuous thermal cycling against steatite antagonists. Volumetric wear was measured at 1000, 10,000, 200,000, and 500,000 cycles.RESULTS:There was a statistically significant difference in mean volumetric wear for Activa Bioactive Restorative (p=0.0081, 95% CI: 0.3973, 0.4982) and Equia Forte HT (p<0.001, 95% CI: 1.2495, 1.8493), but no statistically significant difference in mean volumetric wear for Ionolux (p=0.6653) compared to control. Activa Bioactive Restorative wore approximately 60% less than, and Equia Forte HT twice more than Filtek Supreme Ultra on average, respectively.CONCLUSIONS:Compared to a resin composite, contemporary glass-ionomer-containing restorative materials advertised for use as load-bearing restorations display measurably variable in vitro wear rates.

To keep pace with the rapid advancements in molecular genetics and rare diseases research, we have updated the list of ectodermal dysplasias based on the latest classification approach that was adopted in 2017 by an international panel of experts. For this purpose, we searched the databases PubMed and OMIM for the term "ectodermal dysplasia", referring mainly to changes in the last 5 years. We also tried to obtain information about those diseases on which the last scientific report appeared more than 15 years ago by contacting the authors of the most recent publication. A group of experts, composed of researchers who attended the 8th International Conference on Ectodermal Dysplasias and additional members of the previous classification panel, reviewed the proposed amendments and agreed on a final table listing all 49 currently known ectodermal dysplasias for which the molecular genetic basis has been clarified, including 15 new entities. A newly reported ectodermal dysplasia, linked to the gene LRP6, is described here in more detail. These ectodermal dysplasias, in the strict sense, should be distinguished from syndromes with features of ectodermal dysplasia that are related to genes extraneous to the currently known pathways involved in ectodermal development. The latter group consists of 34 syndromes which had been placed on the previous list of ectodermal dysplasias, but most if not all of them could actually be classified elsewhere. This update should streamline the classification of ectodermal dysplasias, provide guidance to the correct diagnosis of rare disease entities, and facilitate the identification of individuals who could benefit from novel treatment options.

One of the most exciting advances in science and health care that I have witnessed is the progress in understanding the genetics of ourselves and the organisms around us. My passion for genetics had its foundations in my innate curiosity, growing up with a scientist father, and then being challenged with patients with complex hereditary conditions that affect their teeth and craniofacial structures. I will always remember my first interactions with a family with multiple children having amelogenesis imperfecta and the many questions that immediately began to surface. What exactly is this? What caused it? How should I go about best treating it? As these patient-care challenges arose for me in the early 1980s, it became clear that we had limited knowledge at the time to answer these questions. The ensuing 40 years have dramatically changed our understanding of human genetics, its role in health and disease, and its potential for new therapeutics, and I believe, the best is yet to come. The first draft of the human genome was published in 2001, and there are nearly 12,000 publications now listed on PubMed when searching “human genome project.”1International Human Genome Sequencing ConsortiumInitial sequencing and analysis of the human genome.Nature. 2001; 409: 860-921Crossref PubMed Scopus (16946) Google Scholar Developing the initial draft of the genome cost an estimated $300 million.2National Human Genome Research Institute, National Institutes of HealthThe cost of sequencing a human genome. Updated November 1, 2021.https://www.genome.gov/about-genomics/fact-sheets/Sequencing-Human-Genome-costDate accessed: December 9, 2021Google Scholar The $2.7 billion spent on the Human Genome Project resulted in knowledge related to gene sequence, function, and new technologies that fueled dramatic advances in understanding both health and disease.2National Human Genome Research Institute, National Institutes of HealthThe cost of sequencing a human genome. Updated November 1, 2021.https://www.genome.gov/about-genomics/fact-sheets/Sequencing-Human-Genome-costDate accessed: December 9, 2021Google Scholar Today, the cost for whole-genome sequencing is around $1,000.1International Human Genome Sequencing ConsortiumInitial sequencing and analysis of the human genome.Nature. 2001; 409: 860-921Crossref PubMed Scopus (16946) Google Scholar Parallel advances in computer technology have enabled the storage and analysis of massive amounts of genetic information. Each genome has over 3 billion nucleotides, as well as many other variables associated with epigenetic changes. This information is now being integrated to enhance our understanding of the mechanisms underlying the move from genotype to phenotype. The human genome database continues to grow. There are multiple large-scale whole genome sequencing projects sampling different populations across the globe. The United Kingdom just released whole genome data on 200,000 Europeans that will be provided free to researchers.3Kaiser J. 200,000 whole genomes made available for biomedical studies.Science. 2021; 374: 1036Crossref PubMed Scopus (1) Google Scholar The “All of Us” project is working on sequencing the DNA of 1 million people in the United States that will reflect the diversity of our population and its origins.4US Department of Health and Human Services, National Institutes of Health. All of Us research program. Accessed January 4, 2022. https://allofus.nih.gov/Google Scholar Fascinating research is helping unravel the complex interactions between our genome and the environment and the contribution of these interactions in the development of complex traits ranging from autism and asthma to neurologic conditions. Evidence indicates that gene˗environment interactions are important in a variety of birth defects including facial clefts. Our ability to evaluate the genomes and clinical characteristics of large numbers of people with specific clinical traits provides the opportunity to understand the etiology of and develop interventions for these conditions. The importance of host˗environment interaction is readily evident when looking at the complex relationship between humans and the microorganisms that live on and in us. Our immune systems function with input and support from our microbial communities and without these critical interactions we would be unlikely to survive. Our ability to evaluate the genomes and clinical characteristics of large numbers of people with specific clinical traits provides the opportunity to understand the etiology of and develop interventions for these conditions. Our ability to evaluate the genomes and clinical characteristics of large numbers of people with specific clinical traits provides the opportunity to understand the etiology of and develop interventions for these conditions. So how is this investment in research and the acquisition of new knowledge translating to therapies and improved health? Given the typical lag time from discovery to adoption of new therapies, there have been some remarkable achievements. Not the least of these developments has been the use of mRNA vaccines to protect against COVID-19, which was possible because of the ability to sequence the genome of the severe acute respiratory syndrome coronavirus 2, the virus responsible for the pandemic. Identifying changes to the sequence of the viral genome to produce new mutant strains provides the opportunity to adapt new vaccines and better predict the changes that may occur in viral structure and traits, such as transmissibility and virulence. Identifying the molecular basis of conditions such as hypophosphatasia and hypophosphatemic rickets resulted in the development of therapies that are now commercially available. These conditions are associated with early tooth loss and other dental defects, for which there were no effective treatments until recently. These conditions are now treated by replacing the missing enzymes. While the full benefits of these treatments for improving oral health are not yet fully known, early indications from both laboratory and clinical studies are promising. The outcomes for decreased bone and systemic manifestations using these therapies have been dramatic. A variety of new therapeutic approaches are being developed and tested. For example, it is now possible to correct genetic mutations in a person’s stem cells and reintroduce the genetically corrected stem cells into the patient. This therapeutic approach has allowed physicians to replace the epidermis in people with epidermolysis bullosa who experience chronic blistering of the skin.5Hirsch T. Rothoeft T. Teig N. et al.Regeneration of the entire human epidermis using transgenic stem cells.Nature. 2017; 551: 327-332Crossref PubMed Scopus (344) Google Scholar Gene therapy can be used to treat many different conditions. There are hundreds of clinical trials registered at https://www.clinicaltrials.gov that are evaluating a variety of gene therapy and gene transfer protocols to for numerous and diverse conditions. I have no doubt that astounding miracles of medicine will emanate from our increasing knowledge of not only the human genome, but of the genomes of microorganisms and other living species, in addition to careful assessment of phenotypes, protein interactions, and understanding the connectedness of this information as it relates to the complexity and miracle of life. The goals for better prediction of disease and treatment outcomes and precision medicine are becoming a reality, and we have already realized tremendous advances in diagnostics of hereditary conditions and cancer. Novel therapies are now a reality and not just concepts. Considering that the structure of DNA was first resolved in 1953 and the first draft of the human genome was published in 2001, we have made remarkable progress.6Watson J.D. Crick F.H. Molecular structure of nucleic acids; a structure for deoxyribosenucleic acid.Nature. 1953; 171: 737-748Crossref PubMed Scopus (7813) Google Scholar It is rewarding to be able to provide definitive diagnostic information for patients and have the opportunity to discuss therapies that were not available just a few short years ago. We are but at the doorway of being able to fully apply this knowledge that will advance health care and improve people’s lives.

It is estimated that human knowledge doubles at a mind-boggling rate of every 12 hours.1Sorkin S. Thriving in a world of “knowledge half-life.” April 5, 2019. CIO.com.https://www.cio.com/article/219940/thriving-in-a-world-of-knowledge-half-life.htmlDate accessed: August 13, 2022Google Scholar Before development of the internet, information was accessed through books, journals, and peer exchange. Increasingly, with the advent of the internet, machine learning, and sheer computational power, much of that knowledge is now being generated by machines and not humans, which means we can expect the rate of knowledge creation to increase. The computational generation of health care knowledge is transformative and promises to inform our decisions and alter the ways in which we access information.The computational generation of health care knowledge is transformative and promises to inform our decisions and alter the ways in which we access information. The computational generation of health care knowledge is transformative and promises to inform our decisions and alter the ways in which we access information. Oral health care providers typically make multitudes of decisions that directly influence the quality and outcome of the care they provide to every single patient. They make selections, assessments, and determinations of health histories and diagnostic tools, and they interpret and synthesize data in the context of what is known. This knowledge is used to make an informed diagnosis and develop a care- and patient-management approach. The fundamentals of this process are learned during professional school where critical thinking must be an integral part of the learning process. Accessing and interpreting information is no small undertaking, given the speed of change and the sheer volume of data now available. And here is the clinician’s dilemma: It is not humanly possible to keep up with all the changes and information that exist related to oral health, much less all the other important knowledge needed to have a patient-centered health care approach. How can the busy clinician stay abreast of the latest information needed to provide the best care for their patients and communities? Understanding evidence-based health care guidelines is 1 way to keep up with the best knowledge to support decision making and to improve quality of care and, ultimately, patients’ health outcomes. Guidelines directed at helping practitioners improve patient care and safety are not new, but they have evolved. In the 1970s, conferences were held specifically to develop oral health care guidelines.2Removal of third molars: sponsored by the National Institute of Dental Research.Natl Inst Health Consens Dev Conf Summ. 1979; 2: 65-68PubMed Google Scholar I remember attending a national consensus conference at which guidance for health care was discussed and best practices were outlined on the basis of the available science and expert opinion. Although experience and expert opinion are both important, the role of science and the level of evidence supporting decision making and recommendations or guidelines have changed how we can be informed. In many clinical areas, but certainly not all, there is an abundance of knowledge informing evidence-based decision making. However, some practitioners may feel that their patients are not the same as the patients included in a certain guideline’s development. That is a legitimate concern if one were to apply guidelines as the letter of the law without considering other factors. The application of evidence-based practice must consider not only the science informing the practitioner’s decision making but also the patient’s wants and desires and the practitioner’s personal experience in addition to factors such as cultural and economic considerations. Collectively, the practitioner contextualizes this information to move from evidence to decision. Examples of adaption and personalization of a care guideline could include pain management, in which multimodal regimens can be indicated, or the types of materials used for dental restoration, in which cost is a strong determinant. Evidence-based health care emerged in the early 1990s. The American Dental Association (ADA) has played an active role in advancing evidence-based practice since launching its Center for Evidence-Based Dentistry in 2006. Efforts by the ADA and others have established clinical practice guidelines based on scientific evidence, and they have sponsored forums to educate future oral health care providers and practitioners about how this knowledge is developed and how to use it. The ADA has a diverse set of oral health guidelines available on topics ranging from toothpaste use in infants to pit-and-fissure sealants to caries management to periodontal therapy to managing the care of patients with cancer.3Clinical practice guidelines and dental evidence. ADA.org. Accessed September 2, 2022. https://www.ada.org/resources/research/science-and-research-institute/evidence-based-dental-researchGoogle Scholar The full list and complete guideline information are available at the ADA’s website (https://www.ada.org/resources/research/science-and-research-institute/evidence-based-dental-research). In this issue of JADA, the Oral Science Trends article is a review article titled “Strategies for Developing Evidence-Based Clinical Practice Guidelines to Foster Implementation Into Dental Practice.”4Frantsve-Hawley J. Abt E. Carrasco-Labra A. et al.Strategies for developing evidence-based clinical practice guidelines to foster implementation into dental practice.JADA. 2022; 153: 1041-1052Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar This invited review was written by experts in the field who discuss how evidence-based dentistry and guidelines have developed and changed over time. They discuss the limitations of clinical practice guidelines that historically were based on evidence from systematic reviews that summarized and synthesized data from randomized controlled trials. Not all guidelines lend themselves to development and updating from this type of evidence, with the American Heart Association’s prophylaxis guidelines being a prime example. As explored by the authors of this Oral Science Trends review, there are other valuable sources of knowledge that can supply important perspectives and information to help inform a guideline. This includes information from observational studies and the growing volume of information related to mining the massive amounts of data from electronic health records that document millions of oral health care treatments and outcomes. The adoption and implementation of clinical practice guidelines are critical steps in deciding how patient care and outcomes are or are not changed by a guideline. Guidelines showing pit-and-fissure sealants’ effectiveness and the science supporting their use have been available and widely disseminated for over a decade, and yet they still are underused as a caries prevention therapeutic.5Makhija S.K. Gilbert G.H. Funkhouser E. et al.for The National Dental PBRN Collaborative Group. Twenty-month follow-up of occlusal caries lesions deemed questionable at baseline: findings from The National Dental Practice-Based Research Network.JADA. 2014; 145: 1112-1118Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar Our access to data is astonishing, and busy practitioners are challenged to stay informed about the evidence that will guide them toward making the best recommendations and implementing the best therapies and interventions for their patients. Keeping up is no small undertaking. Clinical practice guidelines are 1 important method for busy clinicians to use to gain knowledge about best practices. Although there is a plethora of information available on social media, not all of that information is accurate. One must exercise caution and even skepticism, as almost anything can be posted on the internet, and some information and recommendations are not scientific and can be harmful. Discerning the good from the bad can be difficult. New clinical practice guidelines are being developed as are novel approaches for both gathering knowledge to inform the guidelines and to better understand barriers to adoption and implementation. It is JADA’s vision to advance dentistry with evidence-based knowledge. Helping JADA readers understand and have access to clinical practice guidelines is a crucial element directed at achieving that vision. Knowledge supplies the power to be the best health care provider possible. Dr. Wright is the Bawden Distinguished Professor, Division of Pediatric Dentistry and Public Health, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, and the editor, The Journal of the American Dental Association.