Search

The aim of the present study was to establish a modular platform of poly-L-lysine-heparin (PLL-Hep) polyelectrolyte multilayer (PEM) coatings on titanium surfaces for dual growth factor delivery of recombinant human bone morphogenic protein 2 (rhBMP2) and recombinant human vascular endothelial growth factor 165 (rhVEGF165) in clinically relevant quantities. Release characteristics for both growth factors differed significantly depending on film architecture. rhBMP2 induced activation of alkaline phosphatase in C2C12 cells and proliferation of human mesenchymal stem cells (hMSCs). rhVEGF mediated induction of von Willebrand factor (vWF) in hMSCs and proliferation of human umbilical vein endothelial cells. Osteogenic and angiogenic effects were modified by variation in cross-linking and architecture of the PEMs. By creating multilayer films with distinct zones, release characteristics and proportion of both growth factor delivery could be tuned and surface-activity modified to enhance angiogenic or osteogenic function in various ways. In summary, the system provides a modular platform for growth factor delivery that allows for individual composition and accentuation of angiogenic and osteogenic surface properties.

OBJECTIVE To assess the aetiologic factors, proposed diagnostic means and treatment strategies for neuralgia-inducing cavitational osteonecrosis. METHODS A search of the literature published up to June 2020 was conducted using Medline, the Cochrane Library, PsycINFO, CINAHL and Web of Science. The scientific quality of the evidence was rated according to NIH Quality Assessment Tools. RESULTS 4,051 articles were found, 59 were reviewed in full text, and 29 studies were included. With the exception of hereditary coagulopathies, which were identified as potential risk factors in five studies, suggestions concerning the aetiology varied widely. No gold standard diagnostic mean could be identified. Treatment was most often performed by surgical curettage of the affected bone. Surgical treatment outcomes were equally varied: significant facial pain remission was reported in 66%-100% for periods varying between 2 months to 18 years, whereas no or little relief and recurrences were reported in up to ⅓ of cases. All studies were observational in their design. All investigations were rated as poor quality because of high risk of bias and non-transparent reporting. CONCLUSIONS Evidence concerning the aetiology, diagnosis and treatment of NICO is poor. Prospective diagnostic and therapeutic studies are needed before the usefulness of invasive therapeutic procedures can be evaluated.

The aim of the present study was to develop a collagen/heparin-based multilayer coating on titanium surfaces for retarded release of recombinant human bone morphogenic protein 2 (rhBMP2) to enhance the osteogenic activity of implant surfaces. Polyelectrolyte multilayer (PEM) coatings were constructed on sandblasted/acid-etched surfaces of titanium discs using heparin and collagen. PEM films of ten double layers were produced and overlayed with 200 µL of a rhBMP2 solution containing 15 µg rhBMP2. Subsequently, cross-linking of heparin molecules was performed using EDC/NHS chemistry to immobilize the incorporated rhBMP2. Release characteristics for 3 weeks, induction of Alkaline Phosphatase (ALP) in C2C12 cells and proliferation of human mesenchymal stem cells (hMSCs) were evaluated to analyze the osteogenic capacity of the surface. The coating incorporated 10.5 µg rhBMP2 on average per disc and did not change the surface morphology. The release profile showed a delivery of 14.5% of the incorporated growth factor during the first 24 h with a decline towards the end of the observation period with a total release of 31.3%. Cross-linking reduced the release with an almost complete suppression at 100% cross-linking. Alkaline Phosphatase was significantly increased on day 1 and day 21, indicating that the growth factor bound in the coating remains active and available after 3 weeks. Proliferation of hMSCs was significantly enhanced by the non-cross-linked PEM coating. Nanocoating using collagen/heparin-based PEMs can incorporate clinically relevant amounts of rhBMP2 on titanium surfaces with a retarded release and a sustained enhancement of osteogenic activity without changing the surface morphology.

Adolescence is a delicate phase during life in which self-stigmatization increases and acceptance by peers becomes more important. However, little is known about how adolescents with cleft lip and/or palate experience this stage of life. Therefore, the purpose of this study was to investigate how cleft lip and/or palate (CLP) adolescents are looked at by their peers and how they look at others with/without CLP.In this prospective, cross-sectional study 54 observers (CLP versus control) performed an eye-tracking task and gave attractiveness/ valence ratings. For this purpose, they were shown pictures of patients with and without CLP with neutral or smiling facial expressions.Adolescents with CLP were looked at differently compared to their unaffected peers, with shorter fixations of the eyes and longer fixations of the nose and mouth. Smiling altered the scan path toward the mouth for all faces. Contrary to the control group, adolescents with CLP tended to spend less time fixating the eyes. In the attractiveness/valence ratings, CLP adolescents were rated more negatively.Adolescents with cleft lip and/or palate look differently at peers and are also viewed with an alternate scan path.

Reduced occlusal function is a main characteristic of orthognathic patients. The present study aimed to investigate the extent of therapy-induced functional improvements in occlusal function using a digital diagnostic method.This prospective clinical study included 41 orthognathic patients (24 women and 17 men, median age 27.26 ± 8.2 years) and 10 control patients (5 women and 5 men, median age 29.8 ± 13.5 years) with neutral skeletal and dental configurations. The patients were divided into classes I, II and III based on their cephalometry. Digital occlusal registrations in habitual occlusion in an upright sitting position were taken before (T1) and after (T2) therapy using the T‑Scan Novus (Tekscan, South Boston, MA, USA) application.Class II and III patients showed a significantly less efficient occlusal pattern than the untreated controls regarding total antagonism (p 0.001), time of occlusion (p = 0.004), occlusal asymmetry (p = 0.001), anterior antagonism (p 0.001) and posterior antagonism (p 0.001). After therapy, the occlusal pattern increased in both therapy groups, where class III patients became indistinguishable from the controls, and class II patients differed only in posterior antagonism (p = 0.035).The digital occlusal registration method proved to be a useful diagnostic tool and provided new insights into therapeutic effects in orthognathic patients. By precisely adjusting the occlusal function, masticatory performance improved significantly.Severe malocclusion leads to a significantly lower masticatory performance for patients, which can be improved by orthognathic therapy and captured by digital occlusal registration.ZIELSETZUNG: Die eingeschränkte okklusale Funktion ist ein Hauptmerkmal von Dysgnathiepatient/-innen. Ziel der vorliegenden Studie war es, das Ausmaß von therapiebedingten funktionellen Verbesserungen der okklusalen Funktion mithilfe eines digitalen Registrierverfahrens zu untersuchen.An dieser prospektiven klinischen Studie nahmen 41 Dysgnathiepatient/-innen (24 Frauen, 17 Männer, medianes Alter 27,26 ± 8,2 Jahre) und 10 Kontrollpatient/-innen (5 Frauen, 5 Männer, 29,8 ± 13,5 Jahre) mit skelettal und dental neutraler Konfiguration teil. Die Patienten/-innen wurden anhand ihrer Kephalometrie in die Angle-Klassen I, II und III eingeteilt. Digitale okklusale Registrierungen in habitueller Okklusion und aufrechter Sitzposition wurden vor (T1) und nach (T2) der Therapie unter Anwendung des T‑Scan Novus (Tekscan, South Boston, MA, USA) durchgeführt.Patienten/-innen der Angle-Klassen II und III zeigten ein signifikant weniger effizientes okklusales Muster als die unbehandelten Kontrollen in Bezug auf den Gesamtantagonismus (p 0,001), die Dauer der Okklusion (p = 0,004), die okklusale Asymmetrie (p = 0,001) sowie den anterioren (p 0,001) und den posterioren Antagonismus (p 0,001). Nach der Therapie nahm das okklusale Muster in beiden Therapiegruppen zu, wobei sich die Patient/-innen der Klasse III nicht mehr von den Kontrollen unterschieden, während die Patient/-innen der Klasse II sich nur im posterioren Antagonismus unterschieden (p = 0,035).Die digitale Okklusionsregistrierung erwies sich als nützliches Diagnoseinstrument und lieferte neue Erkenntnisse über die therapeutischen Auswirkungen bei Dysgnathiepatient/-innen. Durch die präzise Einstellung der okklusalen Funktion verbesserte sich die Kaufunktion signifikant.Schwere Zahnfehlstellungen führen bei Patient/-innen zu einer deutlich geringeren Kauleistung, die durch eine kombiniert kieferorthopädisch-kieferchirurgische Therapie verbessert und durch eine digitale Bissregistrierung erfasst werden kann.

Background: To test the hypothesis that cephalometric parameters in two-dimensional routine dental radiographs correlate with the bone supply of intraoral donor regions. Methods: A total of 108 radiographs (36 panoramic radiographs [PRs], 36 lateral cephalometric radiographs [LCRs], and 36 cone-beam computed tomography scans [CBCT]) of 36 patients were analysed. Cephalometric parameters (PR and LCR) were correlated with the bone supply measurement in three-dimensional CBCT scans in three different intraoral donor regions (chin, mandibular retromolar region, and zygomatic alveolar crest). Results: Different mean bone volumes were measured for the chin (3.10 ± 1.11 cm³ SD), the mandibular retromolar region (1.66 ± 0.54 cm³ SD), and the zygomatic alveolar crest (0.17 ± 0.04 cm³ SD). Cephalometric parameters were significantly correlated with the bone dimensions in the chin and the mandibular retromolar region (all p-values < 0.05). Bone volume of the zygomatic alveolar crest exhibited no correlations with cephalometric parameters but significantly correlated with the mandibular retromolar bone volume (p < 0.01). No gender-specific differences were observed with respect to bone volumes in all bone harvesting regions. However, the interforaminal distance in the chin region was significantly higher in the male population (p = 0.001). Conclusion: Routine 2D radiographs can be used during the initial consultation for primary intraoral bone donor site evaluation. This is anticipated to be helpful in defining indications and justifying further diagnostic options such as three-dimensional radiological techniques.

Purpose To test the hypothesis that routine dental radiographs can be used to draw conclusions regarding inferior alveolar nerve (IAN) localization. Methods A total of 108 radiographs (36 orthopantomograms [OPTs], 36 lateral cephalograms [LCs], and 36 cone-beam computed tomograms [CBCTs]) of 36 patients were analyzed. Cephalometric parameters obtained through OPTs and LCs were correlated with CBCT scans for predictability of IAN localization. Results The IAN ran along the lingual half (n = 24) twice as often as in the buccal half (n = 12) in population of the study. The position was always symmetrical contralaterally. No sex-specific correlations were observed (p = 0.34). Lingual nerve courses correlated with enlarged and buccal courses with reduced jaw angles (p = 0.003 / p = 0.010). An increased jaw angle was significantly correlated with a more cranial nerve position; a deep and distal bite position was significantly correlated with a caudal and buccal nerve position (p = 0.020). Moreover, an increase of 1 point in the Hasund score predicted an increased probability of a buccal nerve position by 18.6%. The jaw angle analyzed in OPT, and LC images were positively correlated (r = 0.89, p < 0.001). Conclusions Routine dental radiographs provide meaningful conclusions about IAN localization in the vertical and transverse dimension prior CBCT scans. This finding could be used during the initial consultation and treatment planning to weigh more invasive diagnostic methods further down the line.

In this study, we aimed to evaluate the influence of interactions between mast cells (MCs) and oral squamous cell carcinoma (OSCC) tumor cells on tumor proliferation and invasion rates and identify soluble factors mediating this crosstalk. To this end, MC/OSCC interactions were characterized using the human MC cell line LUVA and the human OSCC cell line PCI-13. The influence of an MC-conditioned (MCM) medium and MC/OSCC co-cultures on the proliferative and invasive properties of the tumor cells was investigated, and the most interesting soluble factors were identified by multiplex ELISA analysis. LUVA/PCI-13 co-cultures increased tumor cell proliferation significantly (p = 0.0164). MCM reduced PCI-13 cell invasion significantly (p = 0.0010). CC chemokine ligand 2 (CCL2) secretion could be detected in PCI-13 monocultures and be significantly (p = 0.0161) increased by LUVA/PCI-13 co-cultures. In summary, the MC/OSCC interaction influences tumor cell characteristics, and CCL2 could be identified as a possible mediator.

OBJECTIVES To systematically assess the literature and report on (1) the frequency of occurrence of buccal soft tissue dehiscence (BSTD) at implants, (2) factors associated with the occurrence of BSTD and (3) treatment outcomes of reconstructive therapy for the coverage of BSTD. MATERIALS AND METHODS Two systematic reviews addressing focused questions related to implant BSTD occurrence, associated factors and the treatment outcomes of BSTD coverage served as the basis for group discussions and the consensus statements. The main findings of the systematic reviews, consensus statements and implications for clinical practice and for future research were formulated within group 3 and were further discussed and reached final approval within the plenary session. RESULTS Buccally positioned implants were the factor most strongly associated with the risk of occurrence of BSTD, followed by thin tissue phenotype. At immediate implants, it was identified that the use of a connective tissue graft (CTG) may act as a protective factor for BSTD. Coverage of BSTD may be achieved with a combination of a coronally advanced flap (CAF) and a connective tissue graft, with or without prosthesis modification/removal, although feasibility of the procedure depends upon multiple local and patient-related factors. Soft tissue substitutes showed limited BSTD coverage. CONCLUSION Correct three-dimensional (3D) positioning of the implant is of utmost relevance to prevent the occurrence of BSTD. If present, BSTD may be covered by CAF +CTG, however the evidence comes from a low number of observational studies. Therefore, future research is needed for the development of further evidence-based clinical recommendations.

Face-bow transfer is an essential step in articulator-based orthognathic surgery planning. However, it can be a source of inaccuracy. Virtual computer-based planning avoids this error through the use of direct patient-related three-dimensional imaging data. The aim of this prospective observational study was to determine the error of face-bow transfer three-dimensionally and correlate it to the different types of malocclusion. Orthognathic surgery performed on 38 patients (10 male, 28 female; mean (standard deviation) age 24.7 (6.9) years) was planned twice: first articulator-based with plaster models and second computer-based with surgery planning software. Both models were digitized and compared regarding the angle between the Frankfort horizontal plane and the occlusal plane. In most cases, the angle in the sagittal dimension was higher in the articulator-based model than in the computer-based model. The angle in the transverse dimension was as often under- as over-represented. The type of malocclusion, i.e. skeletal class, vertical relationship, and degree of asymmetry, had no significant impact on the amount of error. In conclusion, this study indicates that computer-based planning should be considered as an advantageous alternative in orthognathic surgery planning.

Polyelectrolyte multilayers (PEM) are versatile tools used to investigate fundamental interactions between material-related parameters and the resulting performance in stem cell differentiation, respectively, in bone tissue engineering. In the present study, we investigate the suitability of PEMs with a varying collagen content for use as drug carriers for the human bone morphogenetic protein 2 (rhBMP-2). We use three different PEM systems consisting either of the positively charged poly-L-lysine or the glycoprotein collagen type I and the negatively charged glycosaminoglycan heparin. For a specific modification of the loading capacity and the release kinetics, the PEMs were stepwise cross-linked before loading with cytokine. We demonstrate the possibility of immobilizing significant amounts of rhBMP-2 in all multilayer systems and to specifically tune its release via cross-linking. Furthermore, we prove that the drug release of rhBMP-2 plays only a minor role in the differentiation of osteoprogenitor cells. We find a significantly higher influence of the immobilized rhBMP-2 within the collagen-rich coatings that obviously represent an excellent mimicry of the native extracellular matrix. The cytokine immobilized in its bioactive form was able to achieve an increase in orders of magnitude both in the early stages of differentiation and in late calcification compared to the unloaded layers.

Oral cancer therapy is associated with a loss in health-related quality of life (HRQOL) and can also lead to post-traumatic growth (PTG). The current study analyzed the relationship between HRQOL, PTG and influencing clinical factors after treatment. The coherent clinical data of 15 patients were retrospectively analyzed over a 1-year study period. HRQOL and PTG were studied using the University of Washington Quality of Life Version 4 (UW-QOL v4) and Posttraumatic Growth Inventory (PTGI) questionnaires. The results revealed that HRQOL was significantly decreased in a pre- to postoperative manner (P=0.011). Sex demonstrated a nearly significant effect on HRQOL (P=0.058). PTG was experienced the most after surgery, and continuously decreased over the 1-year study period. Patient age had a significant effect on PTG (P=0.040). A significant correlation was also established between HRQOL and PTG (P

Aim To test the hypothesis that the use of rhBMP2 in established defects requires additional growth factors such as rhVEGF to accomplish effective bone repair. Materials and methods Horizontal/vertical defects of 2 cm length and 1 cm height were created bilaterally in the alveolar crest of the maxillae of 18 minipigs together with the extraction of all premolar teeth and one molar tooth on both sides. After 3 months of healing, defects were augmented with 0.5 g particulate PDLLA/CaCO3 composite loaded with 400 µg rhBMP2/50 µg rhVEGF165 on one side and 800 µg rhBMP2 on the other in 12 test animals, whereas defects in six control animals were sham operated and left unfilled on one side and augmented with blank carriers on the other. After 4 and 13 weeks, the animals were evaluated each for area of new bone formation (mm²) and bone density (area %). Results Augmentations with carriers loaded with 800 g µrhBMP2 failed to induce significantly more bone than in the augmentations with unloaded carrier after 4 and 13 weeks (p = .1000, p = .381). Augmentations with carriers loaded with 400 µg rhBMP2 and 50 µg erhVEGF165 resulted in significantly increased bone formation after 13 weeks (p = .024) compared to blank carriers. Soft tissue in augmentations with combined rhBMP2/rhVEGF165 loading exhibited numerous microvessels compared to soft tissue in augmentations with rhBMP2. Conclusions It is concluded that effective bone regeneration in augmentations of established alveolar ridge defects may require the application of rhVEGF additionally to rhBMP2.

Objectives This publication reports on the EAO workshop group 1 summaries, discussions and consensus statements based on four systematic reviews evaluating the impact of timing of dental implant placement and loading. Materials and methods The first of the systematic reviews was on the influence of the timing of implant placement and loading in the biological outcomes of implant-supported fixed partial dentures. The second systematic review evaluated the influence of the timing of implant placement and loading on the aesthetic outcomes in single-tooth implants. The third systematic review was on the long-term outcomes of maxillary single-tooth implants in relation to timing protocols of implant placement and loading and the fourth on patient's perception of timing concepts in implant dentistry. The group evaluated these systematic reviews, provided comments and additions as required and agreed on the relevant consensus statements as well as on clinical and research recommendations. Results Different timings of implant placement/loading presented with high implant survival rates. The systematic reviews evaluated from this working group provided a number of conclusions based on the available/current literature. However, the specific topic of timing is an area that further research is required in order to provide detailed guidelines for the different protocols to be employed.

Objectives Sufficient dental decompensation is crucial for treatment success in combined orthodontic-surgical treatment. The study’s objective was to determine the treatment success and efficiency in sagittal, vertical, and transversal decompensation. Methods This longitudinal, observational study enrolled 52 adult patients, who underwent orthodontic-surgical treatment. Incisor inclinations and positions as well as skeletal changes were assessed pre-treatment (T1), pre-surgical (T2), and post-surgical (T3) by lateral cephalograms and CBCT scans. Results Incisor decompensation was insufficient in all three dimensions. Sagittal: treatment efficiency did not differ between class II and III patients. Vertical: patients with open bite demonstrated pre-surgical bite deepening and insufficient surgical reduction of the maxillomandibular plane angle. Transversal: Dental midline deviations were not adapted to the skeletal asymmetry so that menton deviations were not properly corrected. Conclusions Incisor decompensation was not as successful as requested in all three dimensions and the treatment ideal was seldom achieved. Clinical relevance To improve the skeletal outcome, the orthodontist has to treat the patient with the desired surgical movements in mind and should critically evaluate the pre-surgical incisor decompensation before referral to the surgical team.

Background and Aims To review the regenerative technologies used in bone regeneration: bone grafts, barrier membranes, bioactive factors and cell therapies. Material and Methods Four background review publications served to elaborate this consensus report. Results and Conclusions Biomaterials used as bone grafts must meet specific requirements: biocompatibility, porosity, osteoconductivity, osteoinductivity, surface properties, biodegradability, mechanical properties, angiogenicity, handling and manufacturing processes. Currently used biomaterials have demonstrated advantages and limitations based on the fulfilment of these requirements. Similarly, membranes for guided bone regeneration (GBR ) must fulfil specific properties and potential biological mechanisms to improve their clinical applicability. Pre‐clinical and clinical studies have evaluated the added effect of bone morphogenetic proteins (mainly BMP ‐2) and autologous platelet concentrates (APC s) when used as bioactive agents to enhance bone regeneration. Three main approaches using cell therapies to enhance bone regeneration have been evaluated: (a) “minimally manipulated” whole tissue fractions; (b) ex vivo expanded “uncommitted” stem/progenitor cells; and (c) ex vivo expanded “committed” bone‐/periosteum‐derived cells. Based on the evidence from clinical trials, transplantation of cells, most commonly whole bone marrow aspirates (BMA ) or bone marrow aspirate concentrations (BMAC ), in combination with biomaterial scaffolds has demonstrated an additional effect in sinus augmentation and horizontal ridge augmentation, and comparable bone regeneration to autogenous bone in alveolar cleft repair.

OBJECTIVES: The task of this working group was to update the knowledge about the use of drugs and biologicals affecting healing of soft tissue and bone during implant treatment or procedures associated with it. Moreover, the impact of titanium particles and biocorrosion on complications and implant survival has been analysed. MATERIALS AND METHODS: The literature in the areas of interest (platelet concentrates, antiresorptive drugs as well as implant-host interaction) was screened using systematic reviews for the former two areas, whereas a narrative critical review was performed for the latter topic. Two manuscripts on platelet concentrates, one manuscript on antiresorptive drugs and one manuscript on the effects of biocorrosion, were presented for group analysis with subsequent discussion in the plenum and final consensus approval. RESULTS: Results and conclusions of the individual reviews of the three topics are presented in the respective papers. Conclusions of the group on strengths and weaknesses of available evidence as well as consensus statements and directions for further research are provided in this study. The following papers were subject to group discussions and formed the basis for the consensus statements: Stähli A, Strauss FJ, Gruber R. () The use of platelet-rich-plasma to enhance the outcomes of implant-related therapies: a systematic review Strauss FJ, Stähli A, Gruber R. (2018) The use of platelet-rich-fibrin to enhance the outcomes of implant-related therapies: a systematic review Mombelli A, Hashim D, Cionca N. () What is the impact of titanium particles and bio-corrosion on implant survival and complications? A critical review Stavropoulos A, Bertl K, Pietschmann P, Pandis N, Morten Schiødt, Klinge B. () The effect of antiresorptive drugs on implant therapy: a systematic review. ispartof: CLINICAL ORAL IMPLANTS RESEARCH vol:29 pages:93-99 ispartof: location:SWITZERLAND, Pfaffikon status: published

The chorioallantoic membrane of fertilized chicken eggs in an early phase of breeding presents an approved test situation for the growth and treatment of human cancer cells.These models work due to the inoculation of cells into the membrane that stays within the egg shell during the time of investigation. In this study a modification of this model is presented. Samples of native tumors, rather than cell lines, are transplanted into the membrane and the body of the egg is taken out of the shell and placed in a plastic bowl. These modifications lead to an enhanced accessibility to the chorioallantoic membrane and the surrounding vessels thus facilitating intra venous access and application of pharmaceuticals and a focused radiotherapy. With the current modifications the embryo was kept alive and additionally, the vascularized tumor environment was preserved.

Article, editorial letter

This study investigated the cotransplantation of bone marrow mesenchymal stromal cells (BMSC) and human umbilical cord endothelial cells (HUVEC), and evaluated their contribution to vascular and bone tissue engineering in vivo. To evaluate the success of osteogenic differentiation and timely vascularization of different osteoconductive scaffolds in vivo, we transferred BMSC and HUVEC pre-cultivated calcium carbonate (CaCO3) and hydroxylapatite (HA) matrices into immunocompromised RNU-rats, and analyzed mineralization, expression of osteopontin, and vascular integration via new vessel formation. After in vivo transplantation, pre-cultivated scaffolds demonstrated overall improved mineralization of 44% for CaCO3 (p = 0.01, SD ± 14.3) and 34% for HA (p = 0.001, SD ± 17.8), as well as improved vascularization of 5.6 vessels/0.1 mm2 on CaCO3 (p There is an increasing demand for improved bone regeneration in tissue engineering. Cotransplantation of mesenchymal stromal cells and endothelial cells often demonstrates synergistic improvements in vitro. However, the benefits or superiority of cotransplantation was not evident in vivo and so will require further investigation.

Background and Purpose Adenoid cystic carcinomas (ACC) are characterized by high rate of local recurrence and late distant metastasis. Chromosomal changes in the evolution from primary tumors to metastatic disease of ACC have not been appointed. Here we investigated the chromosomal alterations of 53 primary tumors from ACC patients with different progressive states by shallow whole genome sequencing to identify potential new markers for metastatic spread. Methods Illumina paired-end libraries were generated using DNA from the primary tumor of 53 ACC patients. Fragmented DNA was end-repaired, A-tailed and multiplex sequencing adapters were ligated. Sequence data were mapped to HG19 and a copy-number analysis was conducted using the QDNAseq R package (version 1.10.0). Outliers were removed and data was smoothed by applying the circular binary segmentation algorithm implemented in the R package copynumber version 1.22.0. A modified chromosomal instability (CNI) score was used to analyze deletions and amplifications. Results Cluster analysis of the whole genome sequencing revealed that the frequency of chromosomal aberrations were increased in ACC with local recurrence and distant metastases in comparison to ACC patients with no metastatic spread. Specifically, chromosome 6 and 12 and exclusively the entire chromosome 4 showed an increased frequency of chromosomal alterations with tumor progression. Conclusion Our data show a molecular evolution from primary tumors to local recurrences and distant metastases and pinpoint the critical chromosomal regions involved in this process. These regions should be in the focus of the search for therapeutic targets of progressive ACC.

Incorrect registration of the condylar position in orthognathic surgery is supposed to cause postoperative relapse, condylar resorption and temporomandibular disorders. The aim of this prospective study was to evaluate the influence of general anaesthesia on centric relation (CR). Therefore, CR registered preoperatively in the awake patient and CR registered intraoperatively under general anaesthesia were recorded in 30 patients (14 men, 16 women) undergoing orthognathic surgery (skeletal class I: n=3, II: n=13, III: n=14; symmetric: n=20; asymmetric: n=10). CR records were digitized and, through superimposition on the preoperative cone beam computed tomography of the patient's skull, the superior, anterior and posterior joint space and the volumetric congruence of 120 condyles were analysed. The linear measurements of joint spaces did not demonstrate any clinically relevant discrepancy between the CR measured in the awake and anaesthetized patient. In contrast, volumetric analysis revealed statistically significant differences between both states, with an intraoperative condylar sag predominantly in the posterior-inferior direction. The patient's skeletal class or symmetry had no significant influence on the intraoperative condylar displacement. Thus, the risk of fixing the condyle in an unphysiological position supports the idea of using intraoperative condylar positioning devices to achieve predictable and stable outcomes.

BACKGROUND: The aim was to collate and contrast patient concerns from a range of different head and neck cancer follow-up clinics around the world. Also, we sought to explore the relationship, if any, between responses to the patient concerns inventory (PCI) and overall quality of life (QOL). METHODS: Nineteen units participated with intention of including 100 patients per site as close to a consecutive series as possible in order to minimize selection bias. RESULTS: There were 2136 patients with a median total number of PCI items selected of 5 (2-10). "Fear of the cancer returning" (39%) and "dry mouth" (37%) were most common. Twenty-five percent (524) reported less than good QOL. CONCLUSION: There was considerable variation between units in the number of items selected and in overall QOL, even after allowing for case-mix variables. There was a strong progressive association between the number of PCI items and QOL. peerReviewed

Objective We compared the intraindividual effects of increasing zoledronic acid (ZA) concentrations on osteoblast-like cells with different embryologic origins. Study Design Cultured osteoblast-like cells from mandible and iliac crest bone samples of domestic pigs were exposed to increasing concentrations of ZA (0, 10 −8 , 10 −6 , and 10 −4 M). Proliferation was assessed by cell counting. Receptor activator of nuclear factor kB ligand and osteoprotegerin (OPG) messenger RNA expression were assessed at 0, 1, 4, 7, and 10 days. Results The OPG expression level was higher in the iliac crest than in the mandible. Neither ZA concentration nor the cells' origin affected the expression of receptor activator of nuclear factor kB ligand. At 10 −6 M, OPG expression from both locations reached the same level after 7 days of cultivation, as OPG expression increased to a greater extent in the mandible in comparison to the iliac crest. Conclusion Cultured mandibular osteoblast-like cells reacted more sensitively to high ZA concentrations than did osteoblast-like cells from the iliac crest.

Immobilization of bioactive molecules (BAMs) on a nanometer scale is of great interest for functionalization of implant and scaffold surfaces in current biomaterials research. A system for immobilization of one or more compounds is described, which is based on nanomechanical fixation of single-stranded nucleic acids into an anodic titanium oxide layer and their subsequent hybridization with BAMs conjugated to the respective complementary strands. This paper focuses on further development and in depth understanding of the immobilization system, as some of the major findings established for common sensor applications for immobilization of single-stranded DNA onto gold surfaces cannot be transferred to the TiO2 surface. The first approach concerning the influence of the internal spacer sequence revealed the best performance for a polyadenine based sequence out of four homologous spacer sequences (A30, T30, C30, and G30). This overall best performance of the A30 spacer is attributed to an increased contour length by nucleotide staggering, which resulted in the best protection of the hybridization sequence from unfavorable interactions with the surface or damaging attacks by reactive oxygen species. The second approach comprises the implementation of a lateral spacer, also based on a homologous sequence of A30. Simultaneous as well as sequential adsorption of anchor strands and spacer strands were performed, and it could be shown that a preadsorption with high density of the spacer was most effective to increase hybridization efficiency.