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Orofacial clefts have been associated with specific cleft candidate genes which encode regulatory proteins required for orofacial region development. Cleft candidate genes encode proteins involved with the cleft morphopathogenesis process, but their exact interactions and roles are relatively unclear in human cleft tissue. This study evaluates the presence and correlations of Sonic Hedgehog (SHH), SRY-Box Transcription Factor 3 (SOX3), Wingless-type Family Member 3A (WNT3A) and 9B (WNT9B) protein containing cells in different cleft tissue. Non-syndromic cleft-affected tissue was subdivided into three groups—unilateral cleft lip (UCL) (n = 36), bilateral cleft lip (BCL) (n = 13), cleft palate (CP) (n = 26). Control tissue was obtained from five individuals. Immunohistochemistry was implemented. The semi-quantitative method was used. Non-parametric statistical methods were applied. A significant decrease in SHH was found in BCL and CP tissue. SOX3, WNT3A and WNT9B had a significant decrease in all clefts. Statistically significant correlations were found. The significant decrease in SHH could be associated with BCL and CP pathogenesis. SOX3, WNT3A and WNT9B could have morphopathogenetic involvement in UCL, BCL, and CP. Similar correlations imply the presence of similar pathogenetic mechanisms in different cleft variations.

OBJECTIVES: Artificial intelligence (AI) is swiftly entering oral health services and dentistry, while most providers show limited knowledge and skills to appraise dental AI applications. We aimed to define a core curriculum for both undergraduate and postgraduate education, establishing a minimum set of outcomes learners should acquire when taught about oral and dental AI. METHODS: Existing curricula and other documents focusing on literacy of medical professionals around AI were screened and relevant items extracted. Items were scoped and adapted using expert interviews with members of the IADR's e-oral health group, the ITU/WHO's Focus Group AI for Health and the Association for Dental Education in Europe. Learning outcome levels were defined and each item assigned to a level. Items were systematized into domains and a curricular structure defined. The resulting curriculum was consented using an online Delphi process. RESULTS: Four domains of learning outcomes emerged, with most outcomes being on the "knowledge" level: (1) Basic definitions and terms, the reasoning behind AI and the principle of machine learning, the idea of training, validating and testing models, the definition of reference tests, the contrast between dynamic and static AI, and the problem of AI being a black box and requiring explainability should be known. (2) Use cases, the required types of AI to address them, and the typical setup of AI software for dental purposes should be taught. (3) Evaluation metrics, their interpretation, the relevant impact of AI on patient or societal health outcomes and associated examples should be considered. (4) Issues around generalizability and representativeness, explainability, autonomy and accountability and the need for governance should be highlighted. CONCLUSION: Both educators and learners should consider this core curriculum during planning, conducting and evaluating oral and dental AI education. CLINICAL SIGNIFICANCE: A core curriculum on oral and dental AI may help to increase oral and dental healthcare providers' literacy around AI, allowing them to critically appraise AI applications and to use them consciously and on an informed basis.

The zoonotic parasite Dirofilaria repens has spread toward north in Europe, and cases of autochthonous dirofilariosis caused by D. repens have emerged in the Baltic countries Estonia, Latvia, and Lithuania. We conducted a review on the emergence of dirofilariosis in humans and domestic dogs in these three countries in northeastern Europe. Based on the available literature and reports, the first finding in the Baltic countries was made in Latvia in 2008, followed by the first in Lithuania in 2010, and the first in Estonia in 2012. In all three countries, further findings were reported soon after the first reports. By the end of 2019, autochthonous human D. repens infections had been described from Latvia and Lithuania, and autochthonous canine D. repens infections had been described from all three Baltic countries. While no epidemiological studies estimating prevalence or incidence of the human infections have been published from the three countries, a substantial proportion of investigated dogs have tested positive for microfilariae in studies performed in Latvia and Lithuania. Dirofilariosis is an emerging zoonosis in northern Europe, and the summarized data confirm that D. repens has become established and endemic in the Baltic countries. The available data do not provide a good overview of the situation, and further epidemiological studies are needed. Awareness about the recently emerged zoonotic parasite should be increased among medical doctors, veterinarians, and the general public. Managing this zoonotic infection is a public health challenge that needs to be addressed using a One Health approach. Investigating the spread of D. repens in the Baltic countries could be useful for better preparedness for the anticipated further spread to the Nordic countries.

Clefts of the lip and/or palate (CLP) are visible disruptions of standard facial structure. The aim of our study was to determine a relative number and appearance of the tissue factors in bone of patients with CLP during first time plastic alveolar osteoplasty or rhinoplasty. Immunohistochemistry was performed with matrix metalloproteinase-8 (MMP-8), matrix metalloproteinase-9 (MMP-9), osteopontin (OPN), osteocalcin (OC), Runt-related transcription factor 2 (Runx2), beta-defensin-2 (βdef-2), beta-defensin-3 (βdef-3), interleukin-1 alpha (IL-1α), and interleukin-10 (IL-10). The bone formation was observed by Masson-trichrome (Masson) staining. For the quantification of structures, the semi-quantitative census method was used. Spearman rank order correlation coefficient and Mann-Whitney U test were used for the statistical analysis. A significantly higher number of OPN positive osteocytes was observed in the CLP group when compared to the control group (p=0.002). The number of OC positive osteocytes (p=0.000) and βdef-2 positive osteocytes (p=0.003) was significantly lower in the CLP group in comparison to the control group. Strong, positive correlations between IL-10 and OC (rs=0.608; p=0.002), IL-1α and MMP-9 (rs=0.666; p=0.000), OPN and MMP-8 (rs=0.620; p=0.002) were detected in the CLP group. A tendency for the increased appearance of MMP-8, MMP-9 positive osteocytes of the patients with CLP, suggests elevated tissue remodelling properties. Increased appearance of OPN positive osteocytes in bone of the patients with CLP shows increased bone homeostasis based on seriously decreased mineralization, which may be a possible compensatory reaction to decreased quality of postsurgical bone.

Introduction\ud \ud The Erasmus+O-Health-EDU project aims to gain a comprehensive view of oral health professional (OHP) education in Europe, through the development of web-based surveys and online toolkits. A glossary to facilitate a common language through which academic teams could cooperate and communicate more accurately was identified as a key need within the project. The aim of ARTICULATE was thus to create a shared language, with a European focus, for terms and concepts used in the field of OHP education.\ud \ud \ud \ud Methods\ud \ud The methodology was developed from those published for construction of other glossaries with a circular and iterative process: the creation of content and definitions by a group of experts in OHP education, the testing of “fitness for purpose” of the content, and stakeholder consultation. All creation steps were followed by refinements based on testing results and stakeholder comments. The final glossary was then launched as an online resource including a built-in mechanism for user feedback.\ud \ud \ud \ud Results\ud \ud The scope and structure of the glossary were mapped out at a workshop with 12 dental education experts from 7 European countries. A total of 328 terms were identified, of which 171 were finally included in ARTICULATE. After piloting with a close group of other colleagues, the glossary was opened for external input. Thirty European Deans or Heads of Education assessed the definition of each term as “clear” or “not clear.” A total of 86 definitions were described as “clear” by all individuals. Terms deemed unclear by at least one individual were revisited and changes made to 37 of the definitions. In conjunction with the launch of the glossary, a range of stakeholder organisations were informed and asked to participate in an open global consultation by providing feedback online. Since its launch in June 2021, the ARTICULATE website (https://o-health-edu.org/articulate) has had an average of 500 visits/month. To promote community ownership, forms embedded on the ARTICULATE webpage allow users to give feedback and suggest new terms. A standing taskforce will meet regularly to consider amendments and make changes to ensure that the glossary remains a relevant and up-to-date resource over time.\ud \ud \ud \ud Conclusion\ud \ud ARTICULATE is a unique, evolving, online glossary of terms relating to OHP education, created as a resource for all interested OHP educators. The glossary is a key output of the O-Health-Edu project, which relies on a comprehensive vision of OHP education to address the future oral health needs of the European population.

Bone repair after surgical intervention on cleft lip palate (CLP) depends on the coordinated action of multiple tissue regeneration factors. We determined the relative number and appearance of tissue factors: matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2), bone morphogenetic protein 2/4 (BMP 2/4), transforming growth factor beta (TGF-ß), Wnt3a protein (Wnt3a), Runt-related transcription factor 2 (Runx2), basic fibroblast growth factor (bFGF) and osteoprotegerin in hard tissue of CLP patients during first time surgical intervention. Fourty-three CLP patients with 24 bone and 36 cartilage samples were involved. Immunohistochemistry was used to assess the levels of tissue factors and the semi-quantitative census method was used for quantification of immunological structures. The increased amount of MMP-2 and bFGF positive cells was detected in the CLP group in cartilage and bone (p < 0.05), compared to the controls. A statistically significant (p = 0.012) increased amount of BMP 2/4 positive cells was found in cartilage of CLP patients, in comparison to the control group. Increased appearance of MMP-2, bFGF in hard tissue of the CLP patients indicates the predominance of tissue degradation. Increased number of BMP2/4 positive chondrocytes suggests improved cartilage growth and better regeneration in CLP patients.

This consensus paper reports on the process of developing a renewed vision for Oral Health Professional (OHP) education across Europe, and forms part of a larger EU‐funded collaborative Erasmus+ project, “O‐Health‐Edu.” The vision aligns with the World Health Organisation milestones (2016) and resolutions (2021), and EU4Health programme (2020) objectives ‐ and projects 20 years into the future, to 2040. This longitudinal vision takes a multi‐stakeholder perspective to deliver OHP education that acts in the best interests of both students and patients, and sits within the context of a wider strategy for general health. Included, it is an infographic to help communicate the vision to various stakeholders of OHP education.

Craniofacial morphogenesis is highly complex, as is the anatomical region involved. Errors during this process, resulting in orofacial clefts, occur in more than 400 genetic syndromes. Some cases of cleft lip and/or palate (CLP) are caused by mutations in single genes; however, complex interactions between genetic and environmental factors are considered to be responsible for the majority of non-syndromic CLP development. The aim of the current study was to identify genetic risk factors in patients with isolated cleft palate (CP) by whole genome sequencing. Patients with isolated CP (n = 30) recruited from the Riga Cleft Lip and Palate Centre, Institute of Stomatology, Riga, were analyzed by whole genome sequencing. Pathogenic or likely pathogenic variants were discovered in genes associated with CP (TBX22, COL2A1, FBN1, PCGF2, and KMT2D) in five patients; hence, rare disease variants were identified in 17% of patients with non-syndromic isolated CP. Our results were relevant to routine genetic counselling practice and genetic testing recommendations. Based on our data, we propose that all newborns with orofacial clefts should be offered genetic testing, at least for a panel of known CLP genes. Only if the results are negative and there is no suggestive family history or additional clinical symptoms (which would support additional exome or genome-wide investigation), should multifactorial empiric recurrence risk prediction tools be applied for families.

(1) Background: Despite cleft lips and palates belonging to the most common orofacial congenital anomalies, their morphopathogenesis is not yet fully understood. The study aimed to determine the distribution and relation of cytokines interferon-γ (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-2, IL-7, IL-12, and IL-13 in the cleft affected mucosa of the lip. (2) Materials and Methods: Twenty cleft lip (CL) mucosal samples and seven control tissues of oral cavity mucosa were included in the study. Specimen were obtained during reconstruction surgeries and processed by hematoxylin and eosin staining and immunohistochemistry for IFN-γ, TNF-α, IL-2, IL-7, IL-12, and IL-13. (3) Results: The distribution of cytokines was higher overall in the cleft affected epithelium compared to the connective tissue, with TNF-a, IL-2, and IL-12 displaying the highest number of immunopositive cells. With the exception of IL-2, CL specimen showed higher immunoreactivity. IFN-γ displayed only minor immunoreactivity, with no expression in the control epithelium. Correlation analysis was strongest between CL epithelial IL-13 and IFN-γ (z = 0.71, p &lt, 0.0001). (4) Conclusions: The CLP affected epithelium displays high degrees of plasticity in expressing different cytokines, pointing towards the stimulation of a local adaptive immune response based on consistent inflammatory processes.

Cleft lip and palate are common congenital pathologies that affect the human population worldwide. The formation of cleft lip is associated with multiple genes and their coded proteins, which regulate the development of craniofacial region, but the exact role of these factors is not always clear. The use of morphological studies for evaluation of human cleft-affected tissue has been limited because of insufficiency of available pathological material. The aim of this study was to detect and compare the immunohistochemical expression of cleft candidate gene coded proteins (DLX4, MSX2, HOXB3, SHH, PAX7, SOX3, WNT3A, and FOXE1) in the non-syndromic unilateral cleft lip patient tissue and control group tissue. A semiquantitative counting method was used to evaluate the tissue in biotin-streptavidin-stained slides. Statistically significant differences between the patient and control groups were found for the number of immunoreactive structures for SHH (p = 0.019) and FOXE1 (p = 0.011) in the connective tissue and SOX3 (p = 0.012) in the epithelium. Multiple statistically significant very strong and strong correlations were found between the immunoreactives in cleft-affected tissue. These significant differences and various correlations indicate that multiple morphopathogenetic pathways are possibly involved in unilateral cleft lip pathogenesis. Therefore, we further discuss these possible interactions.

The zoonotic parasite

The prevalence and burden of untreated oral diseases throughout the life course remains high worldwide, and inequalities in oral health and dental care are increasing. This is a major public health issue that is not being enough addressed by the health care systems. To better manage populations' oral health, oral health professionals must be trained to adapt to population needs and societal and technological changes. Furthermore, dental institutions must fulfill their social responsibility by prioritizing educational and research activities that promote advancing individual and community health. In Europe, great variability exists between dental programs within the same country or between countries. This variability is an issue as European graduates can practice around the European Union through mutual recognition of their qualifications. This might lead to inequities in the availability, accessibility, acceptability and quality of health services. The convergence of competencies and quality standards at the international level must thus be better clearly identified, defined and improved. The purpose of the O-Health-Edu, EU funded project, “Advancing Oral Health: A vision for Dental Education” is thus to assess the current situation concerning the oral health professionals' education (OHP) and to identify educational priorities so that future graduating OHPs have competencies aligned with emerging population needs. The project is supported within the KA203 - “Cooperation for Innovation and the Exchange of Good Practices - Strategic Partnerships for higher education” Erasmus program. It began in October 2019 for three years, with eight European university partners and the ADEE (Association for Dental Education in Europe). The firsts steps consist of a scoping review to identify the available information followed by a questionnaire survey to gather more comprehensive data so that to build an opened data source, and a glossary of dental education terms. Key messages Few Information about the current situation of dental education in Europe. Graduates must be equipped with adequate competencies to face populations needs.

Introduction\ud \ud The variability in oral health professional education is likely to impact on the management of oral health needs across Europe. This scoping review forms the initial part of a larger EU‐funded collaborative Erasmus+ project, ‘O‐Health‐Edu’. The aim of this scoping review is to investigate how oral health professional education in Europe is reported.\ud \ud \ud Methods\ud \ud The PRISMA and Arksey & O’Malley methodological frameworks for scoping reviews were used to guide reviewers in answering the research question “How is oral health professional education reported in Europe?”. The search strategy encompassed published literature searches, internet searches and further searching of relevant documents from educational organisations, regulators and professional bodies. Once the search strategy was developed it was sent to key stakeholders for consultation. Sources were reviewed by two authors (JD, JF), and included in the review if they reported on oral health professional education in Europe.\ud \ud \ud Results\ud \ud A total of 508 sources were retrieved from all of the searches. 405 sources were excluded as they did not report on the topic of interest, leaving 103 sources that reported on oral health professional education in Europe. Handsearching the references of published sources lead to a further 41 sources being screened, of which 15 were included. In total, 33 duplications were removed and the final number of included sources was 85. The average year of publication for the included sources was 2007, with sources most commonly published in journals dedicated to dental education. Surveys represented the most common form of reporting. From the data obtained, four broad themes of reporting were evident: Dental education at a Programme Level, Dental education at a Discipline Level, Other Oral Health Professional Education, and, Postgraduate Education and Continuous Professional Development.\ud \ud \ud Conclusion\ud \ud The reporting of dental and oral health professional education in Europe is limited. Whilst there are many useful documents that provide guidelines on dental education, there is limited knowledge on how education is implemented and delivered. There is a greater need for comprehensive educationally driven programme level data on oral health professional education across Europe.

This multicenter study aimed at comparing different techniques of lip and nose repair with or without NAM and primary anterior rhinoplasty in pre-adolescent children. Patients with unilateral clefts of lip, alveolus, and palate who had undergone cleft lip and nose repair were evaluated in a prospective three-centre study using standardized monochromatic, cropped photographs. Four cleft surgeons evaluated the aesthetics of the central part of the face when the patients had reached age ten years. Seventy-six sets of photographs out of 87 patients were evaluated. The overall ratings of lips and noses did not differ much between centres. However, noses of centres 1 (mean 0.74; SD 0.57) and 2 (mean 0.76; SD 0.60) had been rated better than centre 3 (mean 1.32; SD 0.78; p = 0.0078), especially "Deformation of upper part of nostril rim or poor position of alar cartilage". Centre 3 had produced better looking scars (mean 0.33; SD 0.48); p = 0.0036. Within the limitations of the study it seems that NAM and primary anterior rhinoplasty including postoperative nasal stents should be performed whenever possible in order to achieve a favorable shape of the nose and to reduce the need for secondary corrective surgery.

Introduction. Facial morphogenesis occurs from the fourth to the twelfth gestation week, when the cells from nerve crest migrate to the region of face, forming the primary palate. The cleft palate is an abnormality in embryogenesis period, which is characterized by the absence of fusion of palatal shelves. The incidence of cleft lip and palate is one in 700 live births. In recent years the effect of different genes and signaling molecules, including Runx2, Wnt3 and OPG have been studied in the development of cleft palate, because these substances are considered to be regulators of pathogenesis responsible for formation of bone and cartilage tissue and particularly the bone. Aim of the Study. The aim of the work was to evaluate the expression of Runx2, Wnt3 and OPG in palate bone and nasal cartilage for children with cleft palate. Material and methods.Eleven bone and cartilage samples were obtained from 21 children of the lip, soft and hard palate correction surgery. All the patients were diagnosed with clefts of the lip, alveolar process of maxilla, and palate. In the tissue sections using the immunohistochemistry method (IMH), were determined Runx2 (code: AB192256, 1: 250, Abcam GB, rabbit), Wnt3 (code: AB1992, 1: 800, Abcam GB, rabbit), and OPG (code: A0611, 1: 100, The Orbit USA, rabbit) local expression. We used a semi-quantitative census method for quantifying the positive structures. Results. Runx2 expression was observed in five patient bone tissue samples and six patient cartilage tissue samples. Of the Runx2 positive bone tissue, in one case we observed occasional, in two cases- few, in one case- moderate to numerous and in one case numerous positive osteocytes while in tissue of cartilage in two cases we observed few, in one case- few to moderate, in two casesmoderate, and in one case numerous positive chondrocytes. A significant difference in Wnt3 expiation was observed between bone and cartilage tissues. Wnt3 expressing chondrocytes were observed in all samples, where in one case- occasional, in three cases few, in one case-moderate, and in six cases-numerous positive cartilage cells were observed. The expression of the gene in the bone was observed in nine cases, which contained mostly occasional or few positive structures, except in three cases where in one Wnt3 was marked by few to moderate and in two cases numerous positive osteocytes. OPG expression was observed in all samples, but in the cartilage, the expression was more pronounced. In the cartilage in seven cases, there were numerous positive chondrocytes, in one case- few to moderate, in two cases moderate to numerous and in one case few to moderate number of chondrocytes. OPG showed variable expression. In four cases, we observed occasional to few, in one case few to moderate, in one case- moderate, in one case moderate to numerous and in four cases numerous positive bone cells. Conclusion. Cartilage tissue expresses significantly more Runx2, Wnt3 genes and OPG proteins, indicating a greater compensatory tissue capacity. In the case of palate clefts, the high expression of Wnt3 and OPG and lower expression of Runx2 could indicate a significant tissue proliferation which predominates over mineralization and ossification processes.

Background and Aims: Morphogenesis of the upper lip and palate is a complex process involving highly regulated interactions between epithelial and mesenchymal cells. Genetic evidence in humans and mice indicates the involvement of matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) in cleft lip palate (CLP) aetiology. This study investigated whether expression of MMP-2, MMP-8, MMP-9, TIMP-2, and TIMP-4, which are essential for the upper lip and palate fusion, is dysregulated in children with CLP. Methods: Oral mucosa tissue samples were obtained from patients with complete unilateral (CU) CLP (n = 25) and complete bilateral (CB) CLP (n = 19) during corrective plastic surgery and in unaffected control subjects (n = 10). MMPs and TIMPs expression was assessed by immunohistochemistry, and the data were analyzed using the Kruskal - Wallis test with the Bonferroni correction. Results: In CLP patients, MMP-2, TIMP-2 immunoreactivity in the oral mucosa was seen to have a few to abundant structures, but the overall number of MMP-2, TIMP-2-positive structures was greater than that in controls (P < 0.01). The total number of TIMP-4, MMP-9-positive cells showed a significant decrease in the CBCLP compared with that of CUCLP (P < 0.001). MMP-8 expression trends in the CLP group were similar to those of the control group. Conclusions: The results suggest that TIMP-4 and MMP-9 are the main ECM remodeling regulatory proteins expressed in CUCLP affected tissues of the oral mucosa. The increased expression of MMP-2 and TIMP-2 in CLP tissues implicates these factors in the regulation of cell migration during ECM turnover independently of different types of clefts. Investigation of MMP and TIMP expression in tissue samples from patients with CLP appears to be a promising approach to the etiopathogenesis of CLP.

Background and objectives: Cleft lip palate takes the second place among all anomalies. The complex appearance of cytokines and proliferation markers has still not been clarified despite their possible crucial role in cleft tissue. Therefore, the aim of work was the detection of appearance of pro- and anti-inflammatory cytokines and proliferation marker Ki67, and their inter-correlations in cleft affected lip (CAL). Materials and Methods: The lip material was obtained from 16 children aged before primary dentition during plastic surgery. Control was obtained from 7 non-CAL oral tissue. Tissues were stained for IL-1, IL-4, IL-6, IL-8, IL-10 and Ki67 immunohistochemically. Non-parametric statistic, Mann&ndash, Whitney and Spearman&rsquo, s coefficient were used. Results: All cytokines positive cells were observed more into the epithelium. Statistically significant difference was seen between epithelial IL-1, IL-10, IL-8 and Ki67 positive cells and IL-10-, IL-4-containing connective tissue cells in comparison to the control. Strong positive correlation was detected in CAL epithelium between IL-10 and IL-8, IL-10 and IL-4, IL-10 and IL-1, IL-1 and IL-8, IL-1 and IL-4, IL-4 and IL-8, IL-8 and Ki67, IL-10 and Ki67, but moderate&mdash, in connective tissue between IL-1 and IL-10, IL-1 and IL-4. Conclusion: The CAL epithelium is the main source for the interleukins. Rich similar expression of IL-1 and IL-10 suggests the balance between pro-and anti-inflammatory tissue response on basis of dysregulated tissue homeostasis (increase of IL-8). The correlations between the different ILs -1, -4, -8, -10 in CAL epithelium seem to indicate the self-protection compensatory mechanism for intensification of local inflammatory-immune response without involvement of IL-6. The correlations between Ki67 and cytokines indicate the involvement of IL-8 and IL-10 in stimulation of cellular proliferation. IL-4 and IL-10 expression from CAL connective tissue simultaneously to IL-1, IL-4 and IL-10 inter-correlations there suggests the intensification of local immune response regulated probably by main pro-inflammatory cytokine&mdash, IL-1.

Cleft lip and palate are amongst the most common congenital malformations worldwide presenting with variable manifestations. Previous research has been primarily focused on the genetical aspects of its complex and multifactorial etiology. In the present study, we investigated the role of cytokines as mediators of epithelial–mesenchymal crosstalk and local site inflammation in cleft affected infants. Lip material was obtained from 12 children aged before primary dentition who suffered from orofacial clefting. The quantification of 12 cytokines (Interleukin-2,4,5,6,10,12,13,17A, Tumor Necrosis Factor-α, Interferon-γ, Transforming Growth Factor beta-1 and Granulocyte-Colony Stimulating Factor) was done using ELISA. Nonparametric Spearman Rho was used to ascertain the correlation between the expression levels of different cytokines. A significantly strong positive correlation was found between IL-2 and IFN-γ coupled with an IL4/IFN-γ ratio favoring IFN-γ. These findings indicate a shift towards the preferential activation of the Th1 differentiation pathway. Further, a pathological reduction in TGFβ-1 levels was noted, which may contribute to mucosal damage. IL-6 was more highly correlated to IFN-γ and IL-12 indicating its potential proinflammatory role in cleft affected tissues. This preferential activation of Th1 cell differentiation and consistent expression of IL-2,6,13 and TNF-α in cleft patients may indicate certain underlying mechanisms for inflammation mediation at the site of clefting.

The aim of the study was to investigate cleft - affected tissues in children with cleft lip and palate in order to detect appearance of β-defensin, interleukins (IL) and gene proteins.The study group included 10 patients with cleft lip and palate. During nose surgery tissue samples from bone and cartilage have been taken, and stained with immunohistochemistry for β-defensin 2, IL4, IL6, IL7, IL8, IL10 and MSX1, RYK, PAX9, IRF6 gene proteins.Results showed prominent expression of IL10 (mean value 47.28±4.26 in visual field) followed by IL7 (35.62±11.18) in cartilage of patients, but slightly less pronounced expression of IL8 (30.14±8.74), IL6 (22.52±10.88) and IL4 (14.81±6.94). The expression of β-defensin 2 was prominent (34.52±11.79) and similar to expression of IL7 in tissue samples of cartilage. MSX1, PAX9, RYK and IRF6 (17.67±5.94; 16.14±5.52; 16.57±5.22 and 11.86±4.21) in cartilage was less pronounced than interleukins and β-defensin 2. MSX1 (12.44±3.34), PAX9 (6.89±2.14), RYK (11.0±5.92) and IRF6 (9.1±4.76) gene proteins expression in bone showed mostly rare occurrence of positive structures.Significant expression of IL7 and β-defensin 2 and IL10 in cartilage proves the prominent immune response in cleft affected hard tissue. Mostly indistinct MSX1, PAX9, RYK and IRF6 gene proteins expression in bone might be an indicator of not complete cellular differentiation, proliferation and migration events in cleft disordered hard tissue.

Objective: Rhinoplasty in patients with complete unilateral cleft lip and palate (UCLP) is challenging, and the surgical outcome of the nose is complicated to evaluate. The aim of this study was to assess the nasolabial appearance of patients with UCLP compared with a control group. Design: Cross-sectional study. Setting: Riga Cleft Lip and Palate Centre, Latvia. Participants: All consecutive 35 patients born between 1994 and 2004 with nonsyndromic complete UCLP were included. Of 35 patients, 29 came for checkup; the mean age was 14.7 years (range 10-18). In the control group, 35 noncleft participants at 10 years of age were included. Interventions: Nasolabial appearance was evaluated from 3-dimensional images using a 3-dimensional stereo-photogrammetric camera setup (3dMDface System), the results being analysed statistically. Results: In UCLP group, a statistically significant difference between cleft and noncleft side was found only in alar wing length ( P < .05). The difference of nasolabial anthropometric distances in the control group between the left and right side was not significant. The difference between the UCLP group and the control group was significant in all anthropometric distances except the lateral lip length to cupid’s bow. Conclusions: The nasolabial appearance with acceptable symmetry after cleft lip and reconstructive surgery of the nose was achieved. Symmetry of the nasolabial appearance in patients with UCLP differed from those in the control group. The 3D photographs with a proposed set of anthropometric landmarks for evaluation of nasolabial appearance seems to be a convenient, accurate, and noninvasive way to follow and evaluate patients after surgery.

This study aimed to evaluate levels of expression of nestin, CD34 and transforming growth factor β3 (TGFβ3) in facial tissue of children with complete unilateral (CU) and complete bilateral (CB) cleft lip and palate (CLP).Twenty-nine CLP patients were enrolled in this study (18 boys and 11 girls). Tissue samples were collected during primary and repeated plastic surgery correction for CU (n=10) or CB (n=19) cleft palate (age range 3 months - 9 years, 6 months). Immunohistochemistry was used to assess levels of nestin, CD34 and TGFβ3. Positively stained cells were graded semi-quantitatively. Data were analyzed to compare cell counts between CUCLP and CBCLP, and CLP at an age before and during primary dentition and CLP in mixed dentition age patients using the Mann Whitney U-test (P0.05).Moderate to abundant numbers of nestin immunoreactive structures were observed in the oral mucosa. CD34 antibodies labeled all microvessels in lamina propria of the CLP affected tissue, while low numbers of TGFβ3 positive cells were scattered in the connective tissue. There were no statistically significant differences between the study groups.Expression of nestin in complete unilateral and bilateral cleft lip and palate affected soft tissue indicates a potential increase of tissue regeneration. CD34 positive oral mucosa cells suggest increased angiogenesis, while the sporadic expression of TGFβ3 indicates an insignificant role in the maintenance and growth of cleft affected oral mucosa stem or progenitor cells. Nevertheless, scarce expression of TGFβ3 suggests a role in cleft morphopathogenesis.

Rhinoplasty for the cleft lip and palate patient is very challenging and surgical outcome of the nose is difficult to evaluate. Discussions of aesthetic evaluation of the nose in cleft lip and palate patients remain problematical. Many different nose aesthetic evaluation methods have been described in the literature; they differ even among articles published in a single year.To analyse the literature concerning aesthetic evaluation of the nose in cleft lip and palate patients and to identify the most objective method for such evaluation postoperatively.The literature was reviewed using MedLine and PubMed sources dated between January 1996 and December 2014. In total, 118 full text articles in English language were selected. Exclusion criteria were: case reports, surgical reviews, literature review, and single evaluations of nasal function.Measurements were obtained from two-dimensional images in 73 articles. Noses were evaluated from 3D images in 22 and by clinical examination in 15. Other methods were evaluation from dental/facial casts, cephalometric evaluation, computer tomography and video recording. In 26 articles some combination of methods was used.The most popular evaluation method is still two-dimensional photography and measurements using anthropometric facial landmarks. Measurements from three-dimensional images seem to be the most objective method and automated facial anthropometric landmark protraction seems to hold promise for the future.

BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (CL/P) is a common complex birth defect caused by the interaction between multiple genes and environmental factors. METHODS: Five hundred and eighty-seven single nucleotide polymorphisms in 40 candidate genes related to orofacial clefting were tested for association with CL/P in a clefting sample composed of 300 patients and 606 controls from Estonian, Latvian, and Lithuanian populations. RESULTS: In case-control comparisons, the minor alleles of FGF1 rs34010 (p 5 4.56 3 10 24 ), WNT9B rs4968282 (p 5 0.0013), and FOXE1 rs7860144 (p 5 0.0021) were associated with a decreased risk of CL/P. Multiple haplotypes in FGF1, FOXE1, and TIMP2 and haplotypes in WNT9B, PVRL2, and LHX8 were associated with CL/P. The strongest association was found for protective haplotype rs250092/rs34010 GT in the FGF1 gene (p 5 5.01 3 10 24 ). The strongest epistatic interaction was observed between the COL2A1 and WNT3 genes. CONCLUSIONS: Our results provide for the first time evidence implicating FGF1 in the occurrence of CL/P, and support TIMP2 and WNT9B as novel loci predisposing to CL/P. We have also replicated recently reported significant associations between variants in or near FOXE1 and CL/P. It is likely that variation in FOXE1, TIMP2, and the FGF and Wnt signaling pathway genes confers susceptibility to nonsyndromic CL/P in Northeastern European populations. Birth Defects Research (Part A) 91:218–225, 2011. 2011 Wiley-Liss, Inc.

BACKGROUND: Orofacial clefts are among the most common birth defects with a strong genetic component. Nonsyndromic cleft palate (NSCP) is a complex malformation determined by the interaction between multiple genes and environmental risk factors. METHODS: We conducted a case-control association study to investigate the role of 40 candidate genes in predisposition to orofacial clefting. Five hundred ninety-one haplotype tagging single nucleotide polymorphism (tagSNPs) were genotyped in a clefting sample from the Baltic region, composed of 104 patients with nonsyndromic cleft palate and 606 controls from an Estonian, Latvian, and Lithuanian population. RESULTS: In case-control comparisons, the minor alleles of IRF6 rs17389541 (p 5 5.45 3 10 24 ) and COL2A1 rs1793949 (p 5 7.26 3 10 24 ) were associated with increased risk of NSCP. Multiple haplotypes in COL2A1 and COL11A2 and haplotypes in WNT3, FGFR1, and CLPTM1were associated with NSCP. The strongest associations were found for IRF6 haplotype rs17389541/rs9430018 GT (p 5 2.23 3 10 24 ) and COL2A1 haplotype rs12822608/rs6823 GC (p 5 3.68 3 10 24 ). The strongest epistatic interactions were observed between MSX1 and BMP2, FGF1 and PVRL2, and COL2A1 and FGF2 genes. CONCLUSIONS: This study provides for the first time evidence of the implication of IRF6, COL2A1, and WNT3 in the occurrence of NSCP. It is likely that variation in cartilage collagen II and XI genes, IRF6, and the Wnt and FGF signaling pathway genes contributes susceptibility to nonsyndromic cleft palate in Northeastern European populations. Birth Defects Research (Part A) 88:748– 756, 2010. 2010 Wiley-Liss, Inc.

To evaluate the association between AXIN2, CDH1 and IRF6 with oral clefts in a cohort from Latvia.283 unrelated individuals, 93 born with isolated oral clefts and 190 individuals born without any structural abnormalities were evaluated. Cleft type and dental anomalies outside the cleft area were determined by clinical examination. Four SNPs were selected for this study: rs2240308 and rs11867417 in AXIN2; rs9929218 in CDH1; and rs642961 in IRF6. Genotypes were determined by polymerase chain reaction using the Taqman assay method from a genomic DNA sample extracted from whole blood. Allele and genotype frequencies were compared between individuals born with or without oral clefts using the PLINK program.Tooth agenesis was the most frequent dental anomaly found among individuals born with oral clefts (N=10; frequency 10.8%). The allele A in the IRF6 marker rs642961 was associated with all combined types of oral clefts (OR=1.74; CI 95% 1.07-2.82) and with cases with cleft lip with or without cleft palate (OR=1.88, CI 95% 1.15-3.01; p=0.007).The IRF6 AP-2a binding site promoter polymorphism is associated with isolated oral clefts in Latvia.

Cleft lip with or without cleft palate (CLP and CL, respectively) and isolated cleft palate (CP) represent one of the most common human birth defects, with a prevalence of approximately 1 in 300-2500 depending on the population. Formation of non-syndromic CL/CLP and CP arises from the interaction of environmental and genetic factors. The objective of this study was to investigate the association between the BMP4 gene (encoding bone morphogenetic protein 4) and non-syndromic CL/CLP and CP in order to clarify the role of this gene in the aetiology of the malformation in Latvian and Lithuanian populations. We genotyped three markers of the BMP4 gene (rs17563, rs2071047 and rs1957860) in order to perform single marker and haplotype association analyses for Latvian and Lithuanian non-syndromic CL/CLP and CP patients and controls. Transmission disequilibrium test was also conducted for Latvian and Lithuanian proband-parent trios. The case-control analysis revealed that SNP rs2071047 allele A was associated with a decreased risk of CL/CLP in the Latvian population, which was confirmed by the haplotype analysis. A modest association was detected between SNP rs1957860 and CP in the Lithuanian population, where allele C was associated with a decreased risk of this cleft phenotype, corroborating haplotype analysis data. Our findings support a role of the BMP4 gene in the aetiology of non-syndromic CL/CLP and CP in the studied populations.

Aim of our study was complex detection of appearance and distribution of specific signalling proteins and apoptosis in facial tissue of children with complete bilateral cleft lip and palate (CBCLP). MATERIALS AND METHODS. Nineteen CBCLP patients and 11 unaffected subjects were involved in this study. All the tissue samples were proceeded for detection of matrix metalloproteinase-2 (MMP-2), tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), and apoptosis. The intensity of immunostaining was graded semi-quantitatively. Results of the terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) method were obtained by counting apoptosis positive cells in five unintentionally chosen fields of vision. Groups were compared using the Mann-Whitney test. RESULTS. TUNEL-positive oral epithelial cells were significantly increased in the control group when compared with the CBCLP group. Connective tissue cells have a statistically significant lower expression of TIMP-2 in the control group compared to the CBCLP group. CONCLUSIONS. TIMP-2 positive connective tissue cells increasingly found in oral mucosa lamina propria proves the decrease of local apoptosis in CLP patients. Prominent expression of MMP-2 in cleft affected soft tissue indicates a possible increase of tissue remodelling.

OBJECTIVE. To investigate cleft disordered tissue in children with cleft palate and cleft lip with or without alveolar clefting for detection of local tissue growth factors and growth factor receptors and compare findings. Design. Morphological analysis of human tissue. Patients. Three groups were studied: 14 patients with cleft palate at the age from eight months to 18 years and two months, 12 patients with cleft lip with or without alveolar clefting in the age from four months to 15 years and four months and 11 control patients. RESULTS. In general, cleft palate disordered tissue showed more prominent expression of BMP2/4 (z=3.574; p=0.0004) and TGFβ (z=2.127; p=0.033), while expression of TGFBR3 significantly higher was only in connective tissue (z=3.822; p=0.0001). Cleft lip affected tissue showed significantly pronounced expression of FGFR1 in general as well as separately in epithelium. CONCLUSIONS. The marked and statistically significant expression of BMP 2/4 in cleft palate disordered soft tissue probably is delayed, but still proliferation and differentiation as well as tissue, especially, bone remodeling contributing signal. Cleft palate affected tissue show more prominent expression of TGFβ, still the weak regional expression of TGFβ type III receptors prove the disordered tissue growth and changed TGFβ signalling pathway in postnatal pathogenesis. In general, expression of TGFβ, BMP 2/4 and FGFR1 is significantly different, giving evidence to the involvement of these mentioned factors in the cleft severity morphopathogenesis.

A prospective randomized crossover, within-patient, controlled study was performed in 26 healthy patients to test the effect of the prophylactic local use of gauze drain impregnated with chlortetracycline (Aureomycin 3%, Lederle) ointment on postoperative alveolitis formation after surgical removal of 52 bilaterally impacted mandibular third molars. The teeth were removed on two separate occasions; on one side drain was inserted in the socket, and on the other side no drain treatment was used for control. The influence on postoperative pain, swelling, and mouth opening ability was investigated. The results indicated a statistically significant reduction (P = 0.02) in the incidence of postoperative inflammatory complications, defined as postoperative alveolitis, from 35% in the no-drain group to 4% in the drain group. No statistically significant difference was found between the two treatment methods with regard to pain and mouth opening reduction. There was a significant difference between the drain and no-drain treatment with regard to swelling on the 1st postoperative day in favor of the no-drain method. It is concluded that insertion of a chlortetracycline-impregnated drain may be an effective method for reducing postoperative alveolitis formation but has no beneficial effect on pain, swelling, and mouth opening reduction after impacted mandibular third-molar surgery.

Caries is a common disease in humans and has a multifactorial etiology. It has been suggested that children born with cleft lip and/or palate (CL/P) have a higher susceptibility to caries, but data from several independent cohorts does not support this assumption. Previous work from our group suggested DEFB 1 is associated with higher caries experience. Since it is suspected that children born with CL/P have the same risk factors predisposing them to caries as other children of the same ages, the aim was to test if DEFB 1 was associated with caries experience in children born with CL/P.Sixty-nine children born with CL/P (aged 2-12 years) were included. Twenty-seven males and seven females had cleft lip and palate (CLP), six males and seven females had cleft lip (CL) and 13 males and nine females had cleft palate (CP). Caries was evaluated with the DMFT/dmft index by a calibrated evaluator. Two single nucleotide polymorphisms in DEFB 1 were selected (rs11362 and rs1800972) based on being associated with higher caries experience in previous work. Genotyping were carried out by real-time PCR using the Taqman assay method. The statistical analysis was performed between 'low-to-moderate caries experience group' and the 'high caries experience group'. Odds ratio calculations between caries experience and variant alleles and chi-square of Fisher exact tests at a level of significance of 0.05 were used.There was no significant difference for caries experience between cleft types (p = 0.551). An association was found for the marker rs11362 and genotype distribution (p = 0.047). When analyzed in a recessive model, the genotype GG in this polymorphism increased the risk for caries susceptibility by more than 3-times (p = 0.031; OR = 3.16; 95% CI = 0.97-10.62).The genetic variant rs11362 in DEFB 1 influences caries susceptibility in CL/P children. The results support the hypothesis that expression of DEFB 1 in saliva may serve as a biomarker for future caries risk.

AimTo present the development of an exemplar e-module for dental continuing professional development (CPD) provided by dental schools and other dental educational providers.Materials and methodsThe exemplar e-module covered the topic of ‘Sterilisation and cross-infection control in the dental practice’ as this is one of the most recommended topics for dental CPD in Europe. It was developed by a group of topic experts, adult learning and distance learning experts and a technical developer. Major concerns were pedagogy, interoperability, usability and cost reduction. Open-source material was used to reduce the cost of development.ResultsThe e-module was pre-piloted in dental practitioners for usability and then evaluated by experts in the field and dental academics through an electronic questionnaire and an online presentation and discussion at the ADEE 2012 Special Interest Group on DentCPD-Lifelong learning. This facilitated refinement before final production. A Creative Commons License was implemented to ensure the developers’ rights and facilitate wider distribution and access to CPD providers.Discussion and conclusionsThe e-module was developed according to well-defined pedagogical and technical guidelines for developing e-learning material for adult learners. It was structured to promote self-study by directing learners through their study, promoting interaction with the material, offering explanation and providing feedback. Content validity was ensured by extensive review by experts. The next step would be to expand the evaluation to practising dentists in various countries after relevant translations, and adaptations to local policies have been made.

AimsTo provide evidence-based and peer-reviewed recommendations for the development of dental continuing professional development (CPD) learning e-modules.MethodsThe present recommendations are consensus recommendations of the DentCPD project team and were informed by a literature research, consultations from e-learning and IT expert, discussions amongst the participants attending a special interest group during the 2012 ADEE meeting, and feedback from the evaluation procedures of the exemplar e-module (as described in a companion paper within this Supplement). The main focus of these recommendations is on the courses and modules organised and offered by dental schools.Results and discussionE-modules for dental CPD, as well as for other health professionals’ continuing education, have been implemented and evaluated for a number of years. Research shows that the development of e-modules is a team process, undertaken by academics, subject experts, pedagogists, IT and web designers, learning technologists and librarians. The e-module must have clear learning objectives (outcomes), addressing the learners’ individual needs, and must be visually attractive, relevant, interactive, promoting critical thinking and providing feedback. The text, graphics and animations must support the objectives and enable the learning process by creating an attractive, easy to navigate and interactive electronic environment. Technology is usually a concern for learners and tutors; therefore, it must be kept simple and interoperable within different systems and software. The pedagogical and technological proficiency of educators is of paramount importance, yet remains a challenge in many instances.ConclusionsThe development of e-courses and modules for dental CPD is an endeavour undertaken by a group of professionals. It must be underpinned by sound pedagogical and e-learning principles and must incorporate elements for effective visual learning and visual design and a simple, consistent technology.

AimFree movement of dental professionals across the European Union calls for more uniform continuing education in dentistry to ensure up-to-date, high-quality patient care and patient safety. This article provides guidelines for the management and delivery of high-quality continuing professional development (CPD) by European dental schools and other CPD providers.MethodThe guidelines are based on an extensive literature inventory, a survey of existing practices (both available as separate publications), discussions during meetings of the Association for Dental Education in Europe in 2011 and 2012 and debate amongst the members of the DentCPD project team representing six dental schools.ResultsOn the basis of the literature review, survey and discussions, we recommend that (i) every dentist should be given the opportunity for CPD, (ii) providers should be quality-approved and impartial, (iii) educators should be approved, impartial, suitably trained, and with educational expertise, (iv) the mode of CPD delivery should suit the educational activity, with clear learning objectives or outcomes, (v) effort should be made to assess the learning, (vi) participant feedback should be collected and analysed to inform future developments and (vii) uniform use of the pan-European system of learning credit points (ECTS) should be implemented.ConclusionImplementation of these guidelines should make dental CPD more transparent to all relevant parties and facilitate the transferability of earned credits across the European Union. It will also enable better quality control within dentistry, resulting in enhanced dental care and ultimately the improvement in patient safety.

IntroductionIn the context of free movement, EU-citizens need assurance that dental practitioners providing their care have a degree/license to practice that meets EU-standards and that they maintain their knowledge and skills through ongoing education.AimOne aim of the ‘DentCPD’ project (HYPERLINK ‘http://www.dentcpd.org’ www.dentcpd.org) was to identify and agree essential CPD requirements for EU dentists. This paper reports the consensus process and outcomes.MethodsAgreement on core components of CPD was achieved through a three stage process: an online survey of dental educators' (n = 143) views on compulsory topics; a paper-based questionnaire to practitioners (n = 411); leading to a proposal discussed at the Association for Dental Education (ADEE) 2011 Lifelong Learning special interest group (SIG).ResultsFrom the online survey and practitioner questionnaire, high levels of agreement were achieved for medical emergencies (89%), infection control (79%) and the medically compromised patient (71%). The SIG (34 attendees from 16 countries) concluded that these three CPD topics plus radiation protection should be core-compulsory and three CPD topics should be core-recommended (health and safety, pain management, and safeguarding children & vulnerable adults). They also agreed that the teaching of all topics should be underpinned by evidence-based dentistry.ConclusionBuilding four core topics into CPD requirements and making quality-approved education and training available will ensure that all dentists have up-to-date knowledge and skills in topic areas of direct relevance to patient safety. In turn, this will contribute to patients having access to comparably high standards of oral health care across Europe.

BACKGROUND: Cleft lip (CL) with or without palate (CLP) and isolated cleft palate (CP) are etiologically complex diseases with interactions among various environmental and genetic factors. The aim of the current study was to identify association with genetic markers and phenotypic craniofacial data in patients with CL/CLP/CP parents. METHODS: Posteroanterior and lateral digital radiographs of the cranium were obtained from 74 parents of patients with CL/CLP/CP. One hundred seventy-three patients with CL/CLP/CP and 190 controls were enrolled in the study for the association test. Five genetic markers of the IRF6 gene and 14 markers of the 19q13 locus were genotyped. Linear regression analysis was performed for the relationship of cephalometric measurements with genotype data adjusted for age, gender, and cleft type. Chi-square and transmission disequilibrium tests were performed to evaluate differences in alleles of the BCL3 gene. Positive findings were replicated in an independent sample (n = 95) of patients with CL/CLP/CP parents. RESULTS: Genetic markers of the BCL3 gene at 19q13, rs7257231, and rs1979377 in the familial association test and rs10401176 in the case-control association test, were associated with craniofacial phenotype. Carriers of BCL3 allele rs7257231T had longer posterior cranial bases than noncarriers (padjusted = 0.0028), and in the familial-based association test showed the statistically strongest relationship (padjusted = 0.05) to phenotype. Relation of rs7257231 to facial formation was confirmed in the replication group (p = 0.0024). CONCLUSIONS: The results indicate that BCL3, which has functions related to cell adhesion and whose downregulation can cause disruption of ectodermal development, is likely to be important in facial formation. Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc.

Clefts of lip and palate belong to the most common birth defects worldwide. Growth factors and genes play an important role in tissue growth, differentiation and induction and upregulation of growth factors, apoptosis and matrix metalloproteinases might be involved in pathogenesis of facial clefts. The aim of this study was investigation of palate tissue in children with unilateral cleft lip palate for detection of local tissue growth factors, barx1 and apoptosis.We investigated soft and hard palate tissue from 36 children with complete unilateral cleft lip and palate from cleft area.14 children were in age before and primary dentition, but 22 children were in mixed dentition period. We examined the localization of barx1, FGFR1, NGFR, TGFbeta, BMP2/4, MMP2, PGP 9,5 by immunohistochemistry. TUNEL method was performed for detection of apoptotic cells.Abundance of FGFR1 positive cells was seen almost in all cases. FGFR richly stained cells of soft and hard palate tissue. Abundance of NGFR positive cells was detected in basal epithelium, hair follicles, nerve fibers in wall of blood vessels and subepithelium, and was more often seen in children before mixed dentition. TGFbeta has showed intensive expression in epithelium, cartilage and bone in both dentition ages. Chondrocytes, fibroblasts and macrophages expressed MMP2 predominant before mixed dentition. Regional expression of barx1 was observed in epithelium before the mixed dentition, while during mixed dentition gene appeared in hyaline cartilage. TUNEL discovered apoptosis in both dentition ages.FGFR1 and TGFbeta are main tissue stimulating growth factors in both dentition ages. Expression of barx1 appears in cleft lip palate affected structures mainly in mixed dentition ages. NGFR and neuropeptides-containing structures are mainly characteristic in cleft tissue before mixed dentition. Distribution of genes, GF and apoptosis seem to correlate rather with dentition age than to type of CLP.

This study evaluates dental occlusion and dental arch parameters of 5-6 year old children with unilateral cleft lip and palate (UCLP) treated and untreated orthodonticly before lip plastic with noncleft children. The aim of the study was to verify whether early orthodontic treatment improves deciduous dental arch relationship of children with unilateral cleft lip and palate.135 casts of 5-6 year old children from Riga and Vilnius were evaluated. 90 casts from children with UCLP (45 - got early orthodontic treatment, 45 - without early orthodontic treatment) and 45 casts from noncleft children. All patients with UCLP had surgically closed lip and palate; five-Year-Olds, Index was used to assess dental arch relationship of UCLP patients. Measurements of dental arch length, canine and molar arch width was taken similar to Bland and Altman method.the difference of the mean values was tested using t-test between and within groups: UCLP-1 (without early orthodontics), UCLP-2 (treated orthodonticaly before lip plastic) and control group - noncleft children). Measurements were performed by two calibrated orthodontists, mean error was calculated according to the Dalberg method. Measurement error was less than 1 mm. Measurements showed that the occlusion parameters and transverse distance between deciduous molars of UCLP-1 group differed from the occlusion of UCLP-2. Children who had got early orthodontics showed better growth of the maxillae. More cases with positive overjet and meziodistal or distal deciduous molar relationship had treated with early orthodontics. Maxillary width between deciduous molars was statistically significant wider in children with UCLP who had early orthodontic treatment comparing with untreated children. Growth of mandible was not inhibited and did not differ treated and untreated children with UCLP and control group.