Search

Orofacial clefts (OFC) present different phenotypes with a postnatal challenge for oral microbiota development. In order to investigate the impact of OFC on oral microbiota, smear samples from 15 neonates with OFC and 17 neonates without OFC were collected from two oral niches (tongue, cheek) at two time points, i.e. after birth (T0: Ø3d OFC group; Ø2d control group) and 4–5 weeks later (T1: Ø32d OFC group; Ø31d control group). Subsequently, the samples were analyzed using next-generation sequencing. We detected a significant increase of alpha diversity and anaerobic and Gram-negative species from T0 to T1 in both groups. Further, we found that at T1 OFC neonates presented a significantly lower alpha diversity (lowest values for high cleft severity) and significantly higher levels of Enterobacteriaceae (Citrobacter, Enterobacter, Escherichia-Shigella, Klebsiella), Enterococcus, Bifidobacterium, Corynebacterium, Lactocaseibacillus, Staphylococcus, Acinetobacter and Lawsonella compared to controls. Notably, neonates with unilateral and bilateral cleft lip and palate (UCLP/BCLP) presented similarities in beta diversity and a mixture with skin microbiota. However, significant differences were seen in neonates with cleft palate only compared to UCLP/BCLP with higher levels of anaerobic species. Our findings revealed an influence of OFC as well as cleft phenotype and severity on postnatal oral microbiota maturation. [ABSTRACT FROM AUTHOR]

Orofacial clefts (OFC) are frequent congenital malformations characterized by insufficient separation of oral and nasal cavities and require presurgical infant orthopedics and surgical interventions within the first year of life. Wound healing disorders and higher prevalence of gingivitis and plaque levels are well-known challenges in treatment of children with OFC. However, oral inflammatory mediators were not investigated after birth using non-invasive sampling methods so far. In order to investigate the impact of OFC on oral cytokine levels, we collected tongue smear samples from 15 neonates with OFC and 17 control neonates at two time points (T), T0 at first consultation after birth, and T1, 4 to 5 weeks later. The samples were analyzed using multiplex immunoassay. Overall, we found significantly increased cytokine levels (TNF, IL-1ß/-2/-6/-8/-10) in tongue smear samples from neonates with OFC compared to controls, especially at T0. The increase was even more pronounced in neonates with a higher cleft severity. Further, we detected a significant positive correlation between cleft severity score and distinct pro-inflammatory mediators (GM-CSF, IL-1ß, IL-6, IL-8) at T0. Further, we found that breast-milk (bottle) feeding was associated with lower levels of pro-inflammatory cytokines (IL-6/-8) in neonates with OFC compared to formula-fed neonates. Our study demonstrated that neonates with OFC, especially with high cleft severity, are characterized by markedly increased inflammatory mediators in tongue smear samples within the first weeks of life potentially presenting a risk for oral inflammatory diseases. Therefore, an inflammatory monitoring of neonates with (severe) OFC and the encouragement of mother to breast-milk (bottle) feed might be advisable after birth and/or prior to cleft surgery. [ABSTRACT FROM AUTHOR]

Objectives Magnetic resonance imaging (MRI) enables a 3D-volume-imaging without ionizing radiation. Therefore, it was the aim of this study to present a post-processing-free method for cephalometric analysis of a MRI-dataset and to examine whether there is a significant difference between cephalometric analysis of conventional 2D cephalograms and MRI scans. Methods One MRI scan each was performed on three cadaver heads using a 3T-MR-scanner. Cephalometric analysis was conducted directly on the 3D dataset. All reference points were projected onto a virtual sagittal plane that was perpendicular to the Frankfort horizontal plane. Double-sided points were averaged. Cephalometric angles were measured from the projected points. Results were compared with cephalometric measurements on conventional lateral cephalometric radiographs (LCRs). The cephalometric analysis was performed by five raters. Results 390-angle measurements were obtained. The inter-rater reliability was high [intraclass correlation coefficients (ICCs) ≥ 0.74 for all angles]. Differences between the measurements on the cephalograms and MRI scans ranged between –0.91° (–1.88°, 0.07°) and 0.97° (–0.63°, 2.57°) on average and were equivalent with respect to a margin of [–2°, 2°] in all angles except L1—Me-Tgo (Bonferroni-Holm-corrected P < 0.05 in all angles except L1—Me-Tgo). The best match was found for the SNA angle. Conclusion The clinical comparability of the MRI- and LCR-based cephalometry could be stated. Using MRI in orthodontics would reduce radiation exposure and the risk of stochastic radiation damage, which is of importance especially in younger patients. [ABSTRACT FROM AUTHOR]

Background: Halitosis is a relatively inhomogeneous pathology with an extremely high prevalence in the population. Potential risk factors for bad breath include bacterial decomposition of organic material as well as numerous general and systemic diseases. The aim of the present study was to analyze whether certain subgroups of oral and maxillofacial surgery patients have a higher risk of halitosis. Further the impact of halitosis on the patient's quality of life was ascertained. Methods: A total of 127 oral and maxillofacial patients aged between 19 and 86 years were enrolled in this study. On account of their underlining disease, patients were divided into five different investigation groups. The dental examination comprised tongue coating, periodontal screening index (PSI), gingival index (GI), PI (plaque index), DMF-T values as well as non-stimulated saliva flow rates. Halitosis was monitored both organoleptically according to Rosenberg and instrumentally by means of a Halimeter®, which records the volatile sulfur compounds (VSC values in ppm). Patients were further asked to fill out questionnaires regarding their medical history and oral hygiene, oral health (OHIP-14), and quality of life (BDI-II). Results: Halitosis values, which were recorded by a Halimeter® correlated with the objective Rosenberg golden standard method. Furthermore, halitosis values correlated with elevated PSI, GI, and DMF-T values as well as the degree of tongue coating. Patients with oral cancer showed significantly higher VSC values compared to all other groups. No difference in VSC values could be found between all other patient groups. Conclusions: The Halimeter® could be validated as a suitable method for determining halitosis in oral and maxillofacial patients. The significantly increased halitosis values in cancer patients as opposed to all other patient groups suggests the potential of halitosis VSC values as a potential screening method. The development of non-invasive breath tests for diagnosis could be subject of future research. [ABSTRACT FROM AUTHOR]

Genome‐wide association studies (GWAS) have generated unprecedented insights into the genetic etiology of orofacial clefting (OFC). The moderate effect sizes of associated noncoding risk variants and limited access to disease‐relevant tissue represent considerable challenges for biological interpretation of genetic findings. As rare variants with stronger effect sizes are likely to also contribute to OFC, an alternative approach to delineate pathogenic mechanisms is to identify private mutations and/or an increased burden of rare variants in associated regions. This report describes a framework for targeted resequencing at selected noncoding risk loci contributing to nonsyndromic cleft lip with/without cleft palate (nsCL/P), the most frequent OFC subtype. Based on GWAS data, we selected three risk loci and identified candidate regulatory regions (CRRs) through the integration of credible SNP information, epigenetic data from relevant cells/tissues, and conservation scores. The CRRs (total 57 kb) were resequenced in a multiethnic study population (1061 patients; 1591 controls), using single‐molecule molecular inversion probe technology. Combining evidence from in silico variant annotation, pedigree‐ and burden analyses, we identified 16 likely deleterious rare variants that represent new candidates for functional studies in nsCL/P. Our framework is scalable and represents a promising approach to the investigation of additional congenital malformations with multifactorial etiology. [ABSTRACT FROM AUTHOR]

Apart from periodontal ligament fibroblasts, immune cells like macrophages also play an important mediating role in orthodontic tooth movement (OTM). Upon orthodontic force application to malpositioned teeth, macrophages in the periodontal ligament get exposed to both mechanical strain and hypoxic conditions (via a compression of blood vessels). In this study, we assessed the relative impact of orthodontically induced mechanical strain and hypoxic conditions on macrophages for the mediation and regulation of OTM. Macrophages were stimulated with physiological orthodontic compressive forces of 2 g/cm2 for 4 h and 24 h on gas-impermeable or gas-permeable cell culture plates under normoxic or hypoxic cell culture conditions. We quantified expression of genes involved in inflammation (Tnf, Il-6, and Cox-2), extracellular remodelling (Mmp-9), and angiogenesis (Vegf) by RT-qPCR. Furthermore, we analysed HIF-1α, prostaglandin-E2, and VEGF protein expression via immunoblotting or ELISA. Mechanical strain and oxygen supply both differentially affected expression of genes and proteins involved in inflammation and angiogenesis. In this context, we found that HIF-1α protein levels were elevated by combined mechanical strain and hypoxic conditions, whereas gas-permeable plates providing sufficient oxygen supply prevented HIF-1α stabilization at the protein level after pressure application on macrophages. Our results thus indicate that macrophages involved in the mediation of OTM are affected by and respond differently to hypoxic conditions and mechanical compressive strain, which occur concomitantly during OTM, than periodontal ligament fibroblasts (PDLF), thus indicating different roles of these cells in the regulation of OTM at the cellular-molecular level. We further observed that contrary to PDLF HIF-1α stabilization in macrophages is rather induced via the decreased oxygen supply associated with OTM than via mechanotransduction by mechanical strain. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to examine the wear behavior of conical crowns with electroplated gold copings that are used to connect implants and teeth to a removable denture. Gold alloy and zirconium dioxide ceramic crowns were compared. Materials and Methods: Fifteen crowns each were milled for two groups: gold alloy and zirconium dioxide. Each specimen had a 2-degree taper. The electroplated coping was established by direct electroforming. The retentive forces and the correlating distance during insertion and separation were measured after 10,000 wear cycles were applied. The wear testing was separated into a start phase, an initial wear phase, and the long-term wear period. The retention force value and the force-distance integral of the first 0.3 mm of each cycle were calculated. Results: The changes in retention force and integral did not differ significantly between both groups in the start and the initial wear phase. No differences were seen in force development during the long-term wear period. Only the force-distance integral showed a significant difference: the median values of the gold crowns increased slightly, and they decreased slightly for the zirconia crowns. The median force values never fell below 6 N for gold and 4 N for zirconia. Conclusions: Within the limitations of this study, the tested conical crowns showed clinically acceptable retentive properties. As with other retentive elements for dentures, the specimens tested showed the greatest amount of change in retentive forces during the first 2,000 cycles. The development of retention force in both groups was not significantly different. However, the zirconia specimens showed reduced variability, which is preferable in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: The subject of the present study was a systematic comparative analysis of the rheumatoid arthritis (RA)‐induced pathomechanisms in the temporomandibular joint with those of the limb joints using the serum‐induced arthritis K/BxN model. Methods: In 18 BALB/c mice the induction of RA was performed according to the Kouskoff method. Another healthy cohort served as controls (n = 12). Joint swelling of the paws was measured using a micrometer. Functional data were obtained analyzing locomotion. Three‐dimensional examination of the temporomandibular joint was performed with micro‐computed tomography imaging, followed by histological evaluation of the extremity joints and the temporomandibular joint. Additionally, immunohistochemical investigations were carried out to evaluate inflammatory and immunological changes. Results: Measurement of joint swelling showed a significant increase in the diameter of the paws, as well as a decrease in locomotor activity compared to control animals and the time before arthritis induction. Histological and immunohistochemical investigations showed clear signs of inflammation in the extremity joints. In contrast, no histological or immunohistochemical indications of an inflammatory process were detectable in the temporomandibular joint. In addition, the three‐dimensional analysis by micro‐computed tomography of the temporomandibular joints did not show any obvious morphological changes. Conclusion: For the first time, using the K/BxN model we could demonstrate that, due to its anatomical and mechanical conditions, the temporomandibular joint seems to be less susceptible to the initiation of RA compared to limb joints. Therefore, additional investigations are needed on other arthritis models as well, in order to further improve our understanding of the pathogenesis and defense mechanisms of the disease. [ABSTRACT FROM AUTHOR]

Background: Nonsyndromic cleft palate only (nsCPO) is a common and multifactorial form of orofacial clefting. In contrast to successes achieved for the other common form of orofacial clefting, that is, nonsyndromic cleft lip with/without cleft palate (nsCL/P), genome wide association studies (GWAS) of nsCPO have identified only one genome wide significant locus. Aim of the present study was to investigate whether common variants contribute to nsCPO and, if so, to identify novel risk loci. Methods: We genotyped 33 SNPs at 27 candidate loci from 2 previously published nsCPO GWAS in an independent multiethnic sample. It included: (i) a family‐based sample of European ancestry (n = 212); and (ii) two case/control samples of Central European (n = 94/339) and Arabian ancestry (n = 38/231), respectively. A separate association analysis was performed for each genotyped dataset, and meta‐analyses were performed. Results: After association analysis and meta‐analyses, none of the 33 SNPs showed genome‐wide significance. Two variants showed nominally significant association in the imputed GWAS dataset and exhibited a further decrease in p‐value in a European and an overall meta‐analysis including imputed GWAS data, respectively (rs395572: PMetaEU = 3.16 × 10−4; rs6809420: PMetaAll = 2.80 × 10−4). Conclusion: Our findings suggest that there is a limited contribution of common variants to nsCPO. However, the individual effect sizes might be too small for detection of further associations in the present sample sizes. Rare variants may play a more substantial role in nsCPO than in nsCL/P, for which GWAS of smaller sample sizes have identified genome‐wide significant loci. Whole‐exome/genome sequencing studies of nsCPO are now warranted. [ABSTRACT FROM AUTHOR]

Nonsyndromic cleft lip with or without cleft palate (nsCL/P) is one of the most common congenital malformation worldwide, and its etiology involves both genetic and environmental factors. Recent genome‐wide and targeted genetic studies of nsCL/P have identified numerous genetic risk loci, under the hypothesis of a multiplicative mode of inheritance. The present study investigated whether novel nsCL/P risk loci could be identified by analyzing dominant/recessive genetic effects in single nucleotide polymorphism (SNP) data from genome‐wide association studies. For this purpose, a genome‐wide investigation of dominant/recessive common SNP effects was performed in our previously published meta‐analysis data set. Twenty‐four loci were identified as candidate regions. In a subsequent association analysis in an independent study cohort of 224 nsCL/P patients and 986 controls of European descent, none of the loci could be replicated. Therefore, our strategy of identifying novel loci by applying different genetic models did not yield any novel findings, suggesting that recessive/dominant common variation only make a limited contribution to nsCL/P in Europeans. However, we cannot rule out that such effects are present at some of the loci that have previously been identified, or are present in different populations. [ABSTRACT FROM AUTHOR]

Background: Although the headgear appliance has been used extensively to correct anteroposterior discrepancies, its treatment effects have not yet been adequately assessed in an evidence-based manner. Objective: Aim of this systematic review was to assess the therapeutic and adverse effects of early headgear treatment from controlled clinical trials on human patients in an evidence-based manner. Search methods: An unrestricted electronic search of six databases from inception to December 2015. Selection criteria: Randomized and prospective non-randomized controlled trials assessing the effects of headgear treatment on human patients. Data collection and analysis: After duplicate study selection, data extraction, and risk of bias assessment according to the Cochrane guidelines, random-effects meta-analyses of mean differences (MDs) and relative risks (RRs), including their 95% confidence intervals (CIs) were performed, followed by subgroup and sensitivity analyses. Results: A total of 18 unique studies with a total of 930 (56% male/44% female) patients were included. Headgear treatment was associated with a posterior translation of the anterior maxilla border in the short term, as seen by the mean annualized change in the SNA angle (MD = -1.63°/ year; 95% CI = -2.20 to -1.06°/year; high quality evidence) compared to untreated patients. This effect was independent of the rotation of the palatal plane and the inclination of the upper incisors, while a proportional relationship with the initial discrepancy in SNA was seen. The clinical significance of this improvement diminished in the long term, although only limited evidence existed. Additionally, early headgear treatment might decrease the risk of dental trauma during the following years (RR = 0.34; 95% CI = 0.14 to 0.80; moderate quality evidence). Low quality evidence on the effect of headgear on the rotation of the palatal plane, the nasolabial angle, the occlusal outcome, and signs of temporomandibular disorders precluded robust assessments, due to risk of bias, inconsistency, imprecision, and small-study effects. Conclusions: Based on existing trials, headgear is a viable treatment option to modify sagittal growth of the maxilla in the short term in Class II patients with maxillary prognathism. [ABSTRACT FROM AUTHOR]

Objectives: Ectopic, impacted, and supplementary teeth are the number one reason for cross‐sectional imaging in pediatric dentistry. The accurate post‐processing of acquired data sets is crucial to obtain precise, yet also intuitively understandable three‐dimensional (3D) models, which facilitate clinical decision‐making and improve treatment outcomes. Cinematic rendering (CR) is anovel visualization technique using physically based volume rendering to create photorealistic images from DICOM data. The aim of the present study was to tailor pre‐existing CR reconstruction parameters for use in dental imaging with the example of the diagnostic 3D visualization of ectopic, impacted, and supplementary teeth. Methods: CR was employed for the volumetric image visualization of midface CT data sets. Predefined reconstruction parameters were specifically modified to visualize the presented dental pathologies, dentulous jaw, and isolated teeth. The 3D spatial relationship of the teeth, as well as their structural relationship with the antagonizing dentition, could immediately be investigated and highlighted by separate, interactive 3D visualization after segmentation through windowing. Results: To the best of our knowledge, CR has not been implemented for the visualization of supplementary and ectopic teeth segmented from the surrounding bone because the software has not yet provided appropriate customized reconstruction parameters for dental imaging. When employing our new, modified reconstruction parameters, its application presents a fast approach to obtain realistic visualizations of both dental and osseous structures. Conclusions: CR enables dentists and oral surgeons to gain an improved 3D understanding of anatomical structures, allowing for more intuitive treatment planning and patient communication. [ABSTRACT FROM AUTHOR]

Nickel-containing alloys are frequently used in the biomedical field, although, owing to corrosive processes metal ion leaching is inevitable. Due to nickel ion (Ni 2+ ) leaching several adverse effects are described in the literature. However, only a few studies evaluated the genetic profile of Ni 2+ in human cells which is of great importance since nickel-induced effects differ between humans and mice as a result of species-specific receptor variability. Thus, we investigated gene expression induced by Ni 2+ in human monocytes using a transcriptome-wide approach determining new target genes implicated in nickel-induced pathologies. Monocytes were isolated from healthy volunteers of Central European origin using stringent inclusion criteria. Cells were challenged with different Ni 2+ concentrations . Array-based gene expression analysis was performed comprising more than 47,000 transcripts followed by pathway analyses. Transcriptional data were validated by protein and cell surface markers. Ni 2+ significantly influenced the expression of 1385 transcripts in a dose-dependent manner. Apart from known targets (CCL20↑, PTGS2↑, MTs↑, SLCs↑), we identified new candidates implicated in Ni 2+ -elicited processes (various microRNAs↑, INSIG1↑, NAMPT↑, MS4A6A↓, DHRS9↓). Several of these transcripts correspond to immunity, inflammation and were shown to be involved in cellular reactions related to hypersensitivity, cancer, colitis, and encephalitis. Moreover, 459 canonical pathways/signaling, 500 pathologies and 2687 upstream regulators were detected. Protein results validated our findings. To our knowledge, the present systematic transcriptome-wide expression study is the first which explored Ni 2+ -elicited cell responses in human primary monocytes identifying new target genes, pathways and upstream regulators of relevance to diagnostic and therapeutic strategies. Statement of Significance Nickel is widely applied in the biomedical field, although several adverse effects are documented in the literature due to nickel ion (Ni 2+ ) leaching. In humans, allergic reactions like contact dermatitis are the most common adverse effect to Ni 2+ , whereas serious concerns relate to possible systemic and carcinogenic activities. Using a systematic genome-wide transcriptional approach in human primary monocytes unveil new target genes, pathways and upstream regulators implicated in nickel-elicited immune response which are of significance to diagnostic and therapeutic strategies. This approach provides new information of how host-derived immune response contributes to the interaction with antigens and supports the interplay between metal ions and systemic diseases. [ABSTRACT FROM AUTHOR]

Background Nonsyndromic cleft with or without cleft palate (nsCL/P) is a common birth defect. Although genome-wide association studies (GWAS) have identified numerous risk variants, a considerable fraction of the genetic heritability remains unknown. The aim of the present study was to replicate a previous finding that de novo deletions in a 62 kb region of chromosome 7p14 are a risk factor for nsCL/P, using an independent cohort. Methods Data from a published case-control GWAS cohort of 399 patients and 1318 controls were used. Copy number variant (CNV) detection in the 62 kb candidate region of 7p14 was performed using QuantiSNP. Putative CNVs in probands were verified and validated by quantitative polymerase chain reaction. Segregation analyses were performed in family members for whom DNA was available. Results Within the 62 kb candidate region, a deletion of 7.4 kb showed association with nsCL/P (13/387 cases, 20/1300 controls, plowest = 0.024, odds ratio = 2.22). In all families with a sporadic case ( n = 3), the deletion occurred de novo. In multiplex families, both incomplete segregation and incomplete penetrance were observed. Conclusion The present data support the hypothesis that deletions at 7p14 are a common risk factor for nsCL/P. Genome-wide CNV analyses in nsCL/P cohorts are warranted to explore the functional relevance of these deletions and their contribution to nsCL/P, and to determine exact breakpoints. Birth Defects Research (Part A) 106:767-772, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objectives Resin infiltrants have been successfully used in dental medicine preventing the progression of tooth decay in an early phase of caries development. ICON ® is an infiltrant of low-viscosity which penetrates via dentinal tubules into the lesion in dependence of the demineralization depth. Hence, we performed an in vitro study to determine the effect of ICON ® on human dental pulp stem cells (hDPSCs). Methods Using explant technique, primary hDPSCs were collected from extracted teeth. Characterization and isolation were performed with typical mesenchymal stem cell markers (Stro-1, CD73, CD90, CD105) and hDPSCs differentiation was validated by immunofluorescence and flow cytometry. HDPSCs were stimulated with light-cured ICON ® (lc) and non-light-cured ICON ® (nc) conditioned media as well as different TEGDMA concentrations followed by the analysis of cytotoxicity, pro- and anti-inflammatory responses and differentiation using XTT assay, RT-PCR and ELISAs, respectively. Results Initial analysis demonstrated that hDPSCs express characteristic mesenchymal stem cell markers and differentiate into adipocytes, chondrocytes and osteoblasts. Notably, ICON ® nc dramatically reduced cell viability (up to 98.9% after 48 h), whereas ICON ® lc showed only a modest cytotoxicity (10%). Data were in line with cytokine expression demonstrating increased levels of IL-6 and IL-8 as well as decreased IL-10 after ICON ® nc exposure compared to ICON ® lc. ICON ® lc caused almost no alterations of DSPP, whereas ICON ® nc markedly elevated DSPP mRNA levels (130.3-times). A concentration-dependent effect was observed in TEGDMA challenged hDPSCs. Significance ICON ® is a successful minimal invasive technique. However, clinicians should strictly follow manufacturer's instructions to prevent adverse effects. [ABSTRACT FROM AUTHOR]

Chronic periodontitis (CP) is a prevalent pathogen-associated inflammatory disorder characterized by the destruction of tooth-supporting tissues, and linked to several systemic diseases. Both the periodontopathogen Porphyromonas gingivalis (Pg), and the genetically determined host immune response, are hypothesized to play a crucial role in this association. To identify new target genes for CP and its associated systemic diseases, we investigated the transcriptome induced by Pg in human monocytes using a genome-wide approach. Monocytes were isolated from healthy male volunteers of European origin and challenged with the Pg virulence factor LPS. Array-based gene expression analysis comprising >47,000 transcripts was performed followed by pathway analyses. Transcriptional data were validated by protein and cell surface markers. LPS Pg challenge led to the significant induction of 902 transcripts. Besides known periodontitis-associated targets, several new candidates were identified (CCL23↑, INDO↑, GBP 1/4↑, CFB↑, ISG20↑, MIR155HG↑, DHRS9↓). Moreover, various transcripts correspond to the host immune response, and have been linked to cancer, atherosclerosis and arthritis, thus highlighting the systemic impact of CP. Protein data of immunological markers validated our results. The present findings expand understanding of Pg elicited immune responses, and indicate new target genes and pathways of relevance to diagnostic and therapeutic strategies. [ABSTRACT FROM AUTHOR]

A profound understanding of the evolution and anatomy of the viscero- and neurocranium is quintessentially important for orthodontists. This particularly alludes to structures, which are directly targeted by orthodontic therapy such as the maxilla and the mid-palatal suture. The anatomy of the mid-palatal suture of toothed individuals is well described, whereas little is known about sutures' morphological changes after tooth loss. Therefore, the aim of this study was to evaluate the edentulous mid-palatal suture by means of histologic and histomorphometric analysis. Ten mid-palatal sutures of edentulous donors as well as six age- and sex matched dentulous controls were examined. For the histological and histomorphometric analysis (sutural width, obliteration, vascularization and interdigitation) conventional staining protocols (HE, Movat-Pentachrome, Sirius Red) and immunofluorescence (vWF, TRAP) were performed. Histomorphometric analysis was carried out using NIS-elements imaging software. When compared to dentulous controls, the edentulous investigation group showed a decreased vascularization and sutural width as well as an increased sutural obliteration. Notably, a high variability and inhomogeneity within regard the histomorphometric parameters was seen in edentulous samples. The mid-palatal suture of edentulous individuals showed significant morphological differences compared to individuals with toothed jaws. The loss of teeth and thereby functional loading seems to have a considerable impact on sutures' morphology. [ABSTRACT FROM AUTHOR]

Objectives Nickel (Ni) is one of the main metal elements in orthodontic and prosthetic devices. Different effects of Ni are described ranging from an induction of local inflammation to allergy and cancerous/mutagenic properties. Inflammatory reactions are frequently observed in the oral cavity, but the interrelationship of Ni with those events is still unknown. Therefore, we focused on the impact of Ni on inflammation in vitro. Methods In accordance to previous immersion tests of our lab, human gingival fibroblasts (HGFs) ( n = 6) were exposed to a pro-inflammatory environment using interleukin-1 beta (IL-1β) and additionally stimulated with different Ni(II) concentrations (400 and 4000 ng/ml). At varying time points the expression of pro- and anti-inflammatory as well as matrix degeneration proteins, i.e. MMPs, were analyzed. Furthermore, proliferation assays, wound healing tests and the detection of NF-κB activation were conducted. Unstimulated HGFs served as control. Results Our experiments showed that low clinical average Ni(II) levels did not alter pro-inflammatory cytokines significantly compared to control ( p > 0.05). Instead, a 10-fold higher dose up-regulated these mediators significantly in a time-dependent manner ( p < 0.01). This was even more pronounced combining both Ni(II) concentrations with an inflammatory condition ( p < 0.001), MMP expressions were in line with our findings ( p < 0.001). The mRNA data were supported by proliferation and wound closure assays ( p < 0.001). However, the combination of both stimuli induced contradictory results. Analyzing NF-κB activation revealed that our results may be in part attributed to NF-κB. Significance Our in vitro study implicated that Ni(II) has various modifying effects on IL-1β-induced inflammatory processes depending on the concentration. [ABSTRACT FROM AUTHOR]

Background Nonsyndromic orofacial clefting (nsOFC) is among the most common of all congenital disorders and has a genetically complex etiology. Based on embryological and epidemiological data, the phenotype can be differentiated into nonsyndromic cleft lip with or without cleft palate (nsCL/P) and nonsyndromic cleft palate only, with nsCL/P being the most frequent form. Recent genetic research, predominantly performed in populations from Europe and Asia, has identified numerous genetic susceptibility loci for nsCL/P. As only few data are available concerning genetic susceptibility to nsCL/P in Arab populations, we investigated a newly recruited nsOFC sample from Yemen. Methods For each of the 15 currently known nsCL/P risk loci, the top single-nucleotide polymorphism (plus nine back-up variants) were genotyped in 242 nsCL/P cases and 420 healthy controls. Results Single-marker association analysis revealed significant associations for four loci (8q24, 9q22, 10q25, 13q31). The strongest association was for the European high risk locus at 8q24 ( Pcorrected = 5.09 × 10−4; heterozygous odds ratio = 1.74 (1.22-2.47), homozygous odds ratio = 2.47 (1.55-3.93). Five additional loci (1q32.2, 3q12, 8q21, 17q22, 20q12) showed nominal significance that did not withstand correction for multiple testing. Although the six remaining loci (1p22, 1p36, 2p21, 3p11, 15q22, 17p13) failed to reach nominal significance, the risk alleles were in the same direction as in the discovery studies. Conclusion The results suggest that four of the 15 analyzed nsCL/P risk loci which were identified in European and Asian ethnicities significantly confer risk for nsCL/P in Arab populations. Birth Defects Research (Part A) 100:307-313, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

doi: 10.1111/j.1741-2358.2011.00477.x Telescopic crowns: extra-oral and intra-oral retention force measurement - in vitro/in vivo correlation Objective: This study deals with the determination of the retentive forces of telescopic crowns measured extra- and intra-orally and the correlation of these values. Background: The telescopic denture is a well-documented solution for prosthetic rehabilitation for a partially edentulous jaw. Acceptable retention forces are needed to avoid inadvertent removal of the denture during movement of the jaws. Recent literature suggests 3-7 N per attachment to be acceptable. These values are only supported by in vitro studies. In vivo data are scarce, and a correlation of the in vitro and in vivo values is lacking. Material and Methods: Twenty-five combined fixed-removable prostheses with a total of 72 double crowns were used for extra-oral retention force measurement prior to cementation ( in vitro). The intra-oral measurement was performed at 72 defined measuring points of the dentures 4-6 weeks after prosthetic rehabilitation ( in vivo). A specifically designed measuring device was used. Results: The rank correlation showed that the in vitro and in vivo values correlate with each other (Spearman's ρ = 0.5052). Additionally, it was found that the median values measured before (1.97N) insertion of the dentures were significantly lower than after (4.70N) insertion (Mann-Whitney test, p ≤ 0.0001). Conclusion: The retention forces measured before and after insertion of the denture correlate with each other although their dimension is significantly higher after insertion. The reason for this behaviour might be some tilting during removal. Nevertheless, the correlation allows a prediction of the clinically relevant forces by a measurement of the extra-orally measured retentive values. [ABSTRACT FROM AUTHOR]

Maxillofacial hard tissues have several differences compared to bones of other localizations of the human body. These could be due to the different embryological development of the jaw bones compared to the extracranial skeleton. In particular, the immigration of neuroectodermally differentiated cells of the cranial neural crest (CNC) plays an important role. These cells differ from the mesenchymal structures of the extracranial skeleton. In the ontogenesis of the jaw bones, the development via the intermediate stage of the pharyngeal arches is another special developmental feature. The aim of this review was to illustrate how the development of maxillofacial hard tissues occurs via the cranial neural crest and pharyngeal arches, and what significance this could have for relevant pathologies in maxillofacial surgery, dentistry and orthodontic therapy. The pathogenesis of various growth anomalies and certain syndromes will also be discussed. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) binds to soluble guanylyl cyclase (sGC), activates it in a reduced oxidized heme iron state, and generates cyclic Guanosine Monophosphate (cGMP), which results in vasodilatation and inhibition of osteoclast activity. In inflammation, sGC is oxidized and becomes insensitive to NO. NO- and heme-independent activation of sGC requires protein expression of the α1- and β1-subunits. Inflammation of the periodontium induces the resorption of cementum by cementoclasts and the resorption of the alveolar bone by osteoclasts, which can lead to tooth loss. As the presence of sGC in cementoclasts is unknown, we investigated the α1- and β1-subunits of sGC in cementoclasts of healthy and inflamed human periodontium using double immunostaining for CD68 and cathepsin K and compared the findings with those of osteoclasts from the same sections. In comparison to cementoclasts in the healthy periodontium, cementoclasts under inflammatory conditions showed a decreased staining intensity for both α1- and β1-subunits of sGC, indicating reduced protein expression of these subunits. Therefore, pharmacological activation of sGC in inflamed periodontal tissues in an NO- and heme-independent manner could be considered as a new treatment strategy to inhibit cementum resorption. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells, as members of the innate immune system, and natural killer T (NKT) cells, bridging innate and adaptive immunity, play a prominent role in chronic inflammatory diseases and cancerogenesis, yet have scarcely been examined in oral diseases. Therefore, systematic research on the latest literature focusing on NK/NKT cell-mediated mechanisms in periodontal disease, including the time period 1988–2020, was carried out in MEDLINE (PubMed) using a predetermined search strategy, with a final selection of 25 studies. The results showed that NK cells tend to have rather proinflammatory influences via cytokine production, cytotoxic effects, dendritic-cell-crosstalk, and autoimmune reactions, while contrarily, NKT cell-mediated mechanisms were proinflammatory and immunoregulatory, ranging from protective effects via B-cell-regulation, specific antibody production, and the suppression of autoimmunity to destructive effects via cytokine production, dendritic-cell-crosstalk, and T-/B-cell interactions. Since NK cells seem to have a proinflammatory role in periodontitis, further research should focus on the proinflammatory and immunoregulatory properties of NKT cells in order to create, in addition to antibacterial strategies in dental inflammatory disease, novel anti-inflammatory therapeutic approaches modulating host immunity towards dental health. [ABSTRACT FROM AUTHOR]

Orthodontic tooth movement to therapeutically align malpositioned teeth is supposed to impact blood flow in the surrounding tissues. Here, we evaluated actual vascularization in the tension area of the periodontal ligament during experimental tooth movement in rats (N = 8) with magnetic resonance imaging (MRI). We inserted an elastic band between the left upper first and the second rat molar; the right side was not treated and served as control. After four days of tooth movement, we recorded T1-weighted morphologic and dynamic-contrast-enhanced MRI sequences with an animal-specific 7 Tesla MRI to assess of local vascularization. Furthermore, we quantified osteoclasts and monocytes in the periodontal ligament, which are crucial for orthodontic tooth movement, root resorptions as undesirable side effects, as well as the extent of tooth movement using paraffine histology and micro-CT analysis. Data were tested for normal distribution with Shapiro–Wilk tests followed by either a two-tailed paired t-test or a Wilcoxon matched-pairs signed rank test. Significant orthodontic tooth movement was induced within the four days of treatment, as evidenced by increased osteoclast and monocyte activity in the periodontal ligament as well as by µCT analysis. Contrast enhancement was increased at the orthodontically-treated side distally of the moved upper first left molar, indicating increased vascularization at the tension side of the periodontal ligament. Accordingly, we detected reduced time-to-peak and washout rates. Our study using MRI to directly assess local vascularization thus seems to confirm the hypothesis that perfusion is enhanced in tension zones of the periodontal ligament during orthodontic tooth movement. [ABSTRACT FROM AUTHOR]

The human oral microbiota consists of over 700 widespread taxa colonizing the oral cavity in several anatomically diverse oral niches. Lately, sequencing of the 16S rRNA genes has become an acknowledged, culture-independent method to characterize the oral microbiota. However, only a small amount of data are available concerning microbial differences between oral niches in periodontal health and disease. In the context of periodontitis, the cytokine expression in the gingival crevicular fluid has been studied in detail, whereas little is known about the cytokine profile in hard and soft tissue biofilms. In order to characterize oral niches in periodontal health, the oral microbiota and cytokine pattern were analyzed at seven different sites (plaque (P), gingival crevicular fluid (GCF), saliva (S), tongue (T), hard palate (HP), cheek (C) and sublingual area (U)) of 20 young adults using next-generation sequencing and multiplex immunoassays. Site-specific microbial compositions were detected, which clustered into three distinct metaniches ("P-GCF", "S-T-HP" and "C-U") and were associated with niche-/metaniche-specific cytokine profiles. Our findings allow the definition of distinct metaniches according to their microbial composition, partly reflected by their cytokine profile, and provide new insights into microenvironmental similarities between anatomical diverse oral niches. [ABSTRACT FROM AUTHOR]

The periodontal ligament (PDL) is exposed to different kinds of mechanical stresses such as bite force or orthodontic tooth movement. A simple and efficient model to study molecular responses to mechanical stress is the application of compressive force onto primary human periodontal ligament fibroblasts via glass disks. Yet, this model suffers from the need for primary cells from human donors which have a limited proliferative capacity. Here we show that an immortalized cell line, PDL-hTERT, derived from primary human periodontal ligament fibroblasts exhibits characteristic responses to glass disk-mediated compressive force resembling those of primary cells. These responses include induction and secretion of pro-inflammatory markers, changes in expression of extracellular matrix-reorganizing genes and induction of genes related to angiogenesis, osteoblastogenesis and osteoclastogenesis. The fact that PDL-hTERT cells can easily be transfected broadens their usefulness, as molecular gain- and loss-of-function studies become feasible. [ABSTRACT FROM AUTHOR]

Background: Gingival invaginations are a common side effect of orthodontic therapy involving tooth extraction and subsequent space closure. Consequences of gingival invaginations are a jeopardized stability of the space closure and hampered oral hygiene. In a retrospective study, the factor time until initiation of orthodontic space closure after tooth extraction has been identified as a potential risk factor for the development of gingival invaginations. The aim of this pilot study is to proof this hypothesis and to enable a caseload calculation for further clinical trials. The referring question is: is it possible to reduce the number of developing gingival invaginations by initiation of orthodontic space closure after tooth extraction at an early point of time?Design: The intended pilot study is designed as a multicenter randomized controlled clinical trial, comparing the impact of two different time intervals from tooth extraction to initiation of orthodontic space closure on the development of gingival invaginations.Forty participants, men and women in the age range of 11 to 30 years with orthodontically related indication for tooth extraction in the lower jaw, will be randomized 1:1 in one of two treatment groups. In group A the orthodontic tooth movement into the extraction area will be initiated in a time interval 2 to 4 weeks after tooth extraction. In group B the tooth movement will be initiated in a time interval >12 weeks after extraction. A possible effect of these treatment modalities on the development of gingival invaginations will be documented at the moment of space closure or 10 months +/- 14 days after initiation of space closure respectively, by clinical documentation of the primary (reduced number of gingival invagination) and the secondary endpoint (reduction of the severity of gingival invaginations).Trial Registration: Universal Trial Number U1111-1132-6655; German Clinical Trials Register DRKS00004248. [ABSTRACT FROM AUTHOR]

Nonsyndromic cleft lip with/without cleft palate (nsCL/P) and nonsyndromic cleft palate only (nsCPO) are the most frequent subphenotypes of orofacial clefts. A common syndromic form of orofacial clefting is Van der Woude syndrome (VWS) where individuals have CL/P or CPO, often but not always associated with lower lip pits. Recently, ∼5% of VWS-affected individuals were identified with mutations in the grainy head-like 3 gene ( GRHL3 ). To investigate GRHL3 in nonsyndromic clefting, we sequenced its coding region in 576 Europeans with nsCL/P and 96 with nsCPO. Most strikingly, nsCPO-affected individuals had a higher minor allele frequency for rs41268753 (0.099) than control subjects (0.049; p = 1.24 × 10 −2 ). This association was replicated in nsCPO/control cohorts from Latvia, Yemen, and the UK (p combined = 2.63 × 10 −5 ; OR allelic = 2.46 [95% CI 1.6–3.7]) and reached genome-wide significance in combination with imputed data from a GWAS in nsCPO triads (p = 2.73 × 10 −9 ). Notably, rs41268753 is not associated with nsCL/P (p = 0.45). rs41268753 encodes the highly conserved p.Thr454Met (c.1361C>T) (GERP = 5.3), which prediction programs denote as deleterious, has a CADD score of 29.6, and increases protein binding capacity in silico. Sequencing also revealed four novel truncating GRHL3 mutations including two that were de novo in four families, where all nine individuals harboring mutations had nsCPO. This is important for genetic counseling: given that VWS is rare compared to nsCPO, our data suggest that dominant GRHL3 mutations are more likely to cause nonsyndromic than syndromic CPO. Thus, with rare dominant mutations and a common risk variant in the coding region, we have identified an important contribution for GRHL3 in nsCPO. [ABSTRACT FROM AUTHOR]