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Objectives The aim of this investigation was to assess the currently available evidence concerning the complications and risk factors influencing the outcome of autotransplantation of teeth in humans. Materials and methods Electronic searches were conducted to identify randomized controlled and prospective clinical trials. Risk of bias within studies was assessed with the Downs and Black tool. Random-effects meta-analyses were conducted to pool the adverse event rates and relative risks with their 95 % confidence intervals. Risk of bias across studies was assessed with the GRADE framework followed by sensitivity analyses. Results Thirty-eight studies were included in the analysis. Reported complications included the need for extraction, failure, hypermobility, pulp necrosis, pulp obliteration, and root resorption. Pooled complication event rates varied considerably, with small studies (<100 teeth) reporting greater complication rates. The analysis of risk factors was associated with both the primary outcome (extraction need) and secondary outcomes (failure, hypermobility, pulp necrosis, pulp obliteration, root resorption). The stage of root development seems to influence both the future survival, as well as the success of the transplanted teeth. Teeth with open apex were less likely to be extracted in comparison to teeth with closed apex (3 studies; 413 teeth; relative risk 0.3; 95 % confidence interval 0.2–0.6). Conclusions Due to the small number of the contributing studies, their methodological limitations, and the heterogeneous results reported, no firm conclusions can be drawn. Clinical relevance Root development of the donor teeth has been established as one the most important factor related to the success of tooth autotransplantation.

Loeys-Dietz syndrome is a rare connective tissue disorder characterized by life-threatening aortic aneurysm and distinctive craniofacial anomalies. It is caused by mutations along the transforming growth factor beta (TGF-β) signaling pathway (LDS1-6). We previously showed that craniofacial anomalies varied among LDS subtypes and that LDS2, caused by mutations in the TGFBR2 gene, exhibited the most severe and variable phenotype. In this study, we performed a thorough qualitative and quantitative analysis of craniofacial anomalies in a mouse model for LDS2, through micro computed tomography and 3D geometric morphometric analysis at multiple postnatal stages. We show that craniofacial shape in Tgfbr2 G357W/ + mice strongly deviates from their WT littermates from an early age and exhibit high variability and evidence of left–right asymmetry despite the pure genetic background. Cranial doming, shortening of the anterior part of the skull, widening of the space between orbits, reduction of mandibular size, suture fusion in the cranial vault and palate, and abnormal condylar shape were among features that were consistent with the phenotype seen in patients with LDS. Interestingly, several of these features were more prevalent and severe in females than in males, indicating potential sexual dimorphism, further supported by the trend observed in our revisited clinical data.

Background: The maxillary labial frenum (MLF) is a soft tissue fold connecting the upper lip to the alveolar process. Abnormal attachment can cause periodontal, functional, and esthetic problems. Differential diagnosis is important and can prevent unnecessary interventions. This study aims to summarize the current evidence on the assessment and management of abnormal MLF. Methods: A thorough review of the literature was conducted. Five online databases were searched for relevant peer-reviewed human studies. Article screening and data extraction were performed independently by two reviewers using predefined inclusion/exclusion criteria. Information about article type, study design, participants’ characteristics, interventions, and outcomes was extracted and synthesized. Results: 52 articles met the review criteria. MLF is a dynamic structure characterized by a wide normal morphological variation. MLF assessment in infants has not been standardized. Studies in pre-adolescents reported a change in the thickness and position of the MLF observed over time, resulting in a lower prevalence of abnormal MLF morphology. Studies in adolescents and adults reported variable differential diagnosis criteria. Lasers appear as the most advantageous frenectomy modality. Conclusions: There is a need for more objective MLF diagnostic protocols and treatment guidelines, which could prevent unnecessary surgical interventions.

Participant recruitment is one of the most challenging aspects of a clinical trial, directly impacting both the study’s duration and the quality of its results. Therefore, reporting successful recruitment strategies is crucial. This study aimed to document the recruitment tactics and experiences of a research team during a university-based randomized clinical trial, conducted as part of a clinical research immersion program. Recruitment took place from October 2021 to October 2022. Before the study commenced, study team members received formal training in clinical trial participant recruitment from the Principal Investigator. The recruitment strategies were integrated into initial study design, which was approved by the Institutional Review Board. A multimodal approach was employed, incorporating both direct and indirect recruitment methods. These strategies successfully met the enrollment target within the twelve-month period. Throughout the process, team members acquired valuable knowledge in recruitment design and implementation, along with transferable interpersonal and networking skills. In-person recruitment was the most efficient and cost-effective strategy, followed by personal referrals. The primary challenge was accommodating participants’ availability. Other study teams should consider these recruitment strategies during their study designs. Additionally, the knowledge and skills gained by this study team underscore the value of experiential learning in research education.

Non-syndromic orofacial clefts encompass a range of morphological changes affecting the oral cavity and the craniofacial skeleton, of which the genetic and epigenetic etiologic factors remain largely unknown. The objective of this study is to explore the contribution of underlying dentofacial deformities (also known as skeletal malocclusions) in the craniofacial morphology of non-syndromic cleft lip and palate patients (nsCLP). For that purpose, geometric morphometric analysis was performed using full skull cone beam computed tomography (CBCT) images of patients with nsCLP (n = 30), normocephalic controls (n = 60), as well as to sex- and ethnicity- matched patients with an equivalent dentofacial deformity (n = 30). Our outcome measures were shape differences among the groups quantified via principal component analysis and associated principal component loadings, as well as mean shape differences quantified via a Procrustes distance among groups. According to our results, despite the shape differences among all three groups, the nsCLP group shares many morphological similarities in the maxilla and mandible with the dentofacial deformity group. Therefore, the dentoskeletal phenotype in nsCLP could be the result of the cleft and the coexisting dentofacial deformity and not simply the impact of the cleft.

In this case report, we focus on Muenke syndrome (MS), a disease caused by the p.Pro250Arg variant in fibroblast growth factor receptor 3 (FGFR3) and characterized by uni- or bilateral coronal suture synostosis, macrocephaly without craniosynostosis, dysmorphic craniofacial features, and dental malocclusion. The clinical findings of MS are further complicated by variable expression of phenotypic traits and incomplete penetrance. As such, unraveling the mechanisms behind MS will require a comprehensive and systematic way of phenotyping patients to precisely identify the impact of the mutation variant on craniofacial development. To establish this framework, we quantitatively delineated the craniofacial phenotype of an individual with MS and compared this to his unaffected parents using three-dimensional cephalometric analysis of cone beam computed tomography scans and geometric morphometric analysis, in addition to an extensive clinical evaluation. Secondly, given the utility of human induced pluripotent stem cells (hiPSCs) as a patient-specific investigative tool, we also generated the first hiPSCs derived from a family trio, the proband and his unaffected parents as controls, with detailed characterization of all cell lines. This report provides a starting point for evaluating the mechanistic underpinning of the craniofacial development in MS with the goal of linking specific clinical manifestations to molecular insights gained from hiPSC-based disease modeling.

BackgroundElevated transforming growth factor-beta (TGF-β) signalling has been implicated in the pathogenesis of Loeys-Dietz syndrome (LDS) and Shprintzen-Goldberg syndrome (SGS). In this study, we provide a qualitative and quantitative analysis of the craniofacial and functional features among the LDS subtypes and SGS.MethodsWe explore the variability within and across a cohort of 44 patients through deep clinical phenotyping, three-dimensional (3D) facial photo surface analysis, cephalometric and geometric morphometric analyses of cone-beam CT scans.ResultsThe most common craniofacial features detected in this cohort include mandibular retrognathism (84%), flat midface projection (84%), abnormal eye shape (73%), low-set ears (73%), abnormal nose (66%) and lip shape (64%), hypertelorism (41%) and a relatively high prevalence of nystagmus/strabismus (43%), temporomandibular joint disorders (38%) and obstructive sleep apnoea (23%). 3D cephalometric analysis demonstrated an increased cranial base angle with shortened anterior cranial base and underdevelopment of the maxilla and mandible, with evidence of a reduced pharyngeal airway in 55% of those analysed. Geometric morphometric analysis confirmed that the greatest craniofacial shape variation was among patients with LDS type 2, with distinct clustering of patients with SGS.ConclusionsThis comprehensive phenotypic approach identifies developmental abnormalities that segregate to mutation variants along the TGF-β signalling pathway, with a particularly severe phenotype associated with TGFBR2 and SKI mutations. Multimodality assessment of craniofacial anomalies objectively reveals the impact of mutations of the TGF-β pathway with perturbations associated with the cranium and cranial base with severe downstream effects on the orbit, maxilla and mandible with the resultant clinical phenotypes.

Introduction: Oral cancer is a serious health problem with an increasing incidence worldwide. Researchers have studied the potential anti-cancerous action of vitamin D and its association with several cancers including oral cancer. The purpose of this scoping review is to synthesize the existing literature on the role of vitamin D on oral cancer. Methods: A scoping review of the literature was conducted using the framework developed by Arkey and O’Malley and the PRISMA-ScR guidelines. Nine databases were searched for peer-reviewed human studies published in English that either investigated the association of vitamin D with, or its impact on either the prevention or treatment of oral cancer. The authors then extracted data using a predefined form to summarize information about article type, study design, participant characteristics, interventions, and outcomes. Results: Fifteen articles met the review criteria. Among the 15 studies, 11 were case–control, 3 were cohort studies, and 1 was a clinical trial. In four studies, the evidence supported a preventive action of vitamin D against oral cancer and a reduction in the negative side effects associated with chemo- and radiotherapy. Several studies that focused on genetic polymorphisms and the expression of the 1,25 dihydroxyvitamin D3 receptor (VDR) suggested significant associations with vitamin D and increased oral cancer risk and worse survival rates. In contrast, two studies did not reveal a strong association between vitamin D and oral cancer. Conclusions: The current evidence suggests an association between vitamin D deficiency and an increased risk of oral cancer. VDR gene polymorphisms might also be a part of future preventive and therapeutic strategies against oral cancer. Carefully designed studies are required to explore and define what role, if any, vitamin D might play in the prevention and treatment of oral cancer.

Background Loeys-Dietz syndrome (LDS), an autosomal dominant rare connective tissue disorder, has multisystemic manifestations, characterised by vascular tortuosity, aneurysms and craniofacial manifestations. Based on the associated gene mutations along the transforming growth factor-beta (TGF-β) pathway, LDS is presently classified into six subtypes. Methods We present the oro-dental features of a cohort of 40 patients with LDS from five subtypes. Results The most common oro-dental manifestations were the presence of a high-arched and narrow palate, and enamel defects. Other common characteristics included bifid uvula, submucous cleft palate, malocclusion, dental crowding and delayed eruption of permanent teeth. Both deciduous and permanent teeth had enamel defects in some individuals. We established a grading system to measure the severity of enamel defects, and we determined that the severity of the enamel anomalies in LDS is subtype-dependent. In specific, patients with TGF-β receptor II mutations (LDS2) presented with the most severe enamel defects, followed by patients with TGF-β receptor I mutations (LDS1). LDS2 patients had higher frequency of oro-dental deformities in general. Across all five subtypes, as well as within each subtype, enamel defects exhibited incomplete penetrance and variable expression, which is not associated with the location of the gene mutations. Conclusion This study describes, in detail, the oro-dental manifestations in a cohort of LDS, and we conclude that LDS2 has the most severely affected phenotype. This extensive characterisation, as well as some identified distinguishing features can significantly aid dental and medical care providers in the diagnosis and clinical management of patients with this rare connective tissue disorder.

Microtubules are formed from heterodimers of alpha- and beta-tubulin, each of which has multiple isoforms encoded by separate genes. Pathogenic missense variants in multiple different tubulin isoforms cause brain malformations. Missense mutations in TUBB3, which encodes the neuron-specific beta-tubulin isotype, can cause congenital fibrosis of the extraocular muscles type 3 (CFEOM3) and/or malformations of cortical development, with distinct genotype–phenotype correlations. Here, we report fourteen individuals from thirteen unrelated families, each of whom harbors the identical NM_006086.4 (TUBB3):c.785G>A (p.Arg262His) variant resulting in a phenotype we refer to as the TUBB3 R262H syndrome. The affected individuals present at birth with ptosis, ophthalmoplegia, exotropia, facial weakness, facial dysmorphisms, and, in most cases, distal congenital joint contractures, and subsequently develop intellectual disabilities, gait disorders with proximal joint contractures, Kallmann syndrome (hypogonadotropic hypogonadism and anosmia), and a progressive peripheral neuropathy during the first decade of life. Subsets may also have vocal cord paralysis, auditory dysfunction, cyclic vomiting, and/or tachycardia at rest. All fourteen subjects share a recognizable set of brain malformations, including hypoplasia of the corpus callosum and anterior commissure, basal ganglia malformations, absent olfactory bulbs and sulci, and subtle cerebellar malformations. While similar, individuals with the TUBB3 R262H syndrome can be distinguished from individuals with the TUBB3 E410K syndrome by the presence of congenital and acquired joint contractures, an earlier onset peripheral neuropathy, impaired gait, and basal ganglia malformations.