Assessment of oropharyngeal respiratory volume and sleep apnoea scores using peripheral arterial tonometry may improve diagnosis and treatment planning of combined dysgnathia therapy approaches.

BACKGROUND: Increased daytime sleepiness is a frequently reported symptom in patients with pronounced dysgnathia. OBJECTIVES: This study investigated possible correlations using home peripheral arterial tonometry (PAT) and oropharyngeal airway volume determination in patients with dysgnathia and daytime sleepiness. METHODS: Twenty patients (13 male, median age 27.6 ± 6.8 years) with abnormal sleep history and 10 skeletal neutral configured controls (6 male, median age 29.5 ± 4.2 years) with normal sleep history were examined. Patients and controls were evaluated for apnoea-hypopnoea index (AHI), respiratory disturbance index (RDI), oxygen desaturation index (ODI), snoring volume (dB), total sleep time (TST) and REM-percentage (REM). Airway volumetry was measured via CBCT. Individual user experience for PAT was assessed using the User Experience Questionnaire (UEQ). RESULTS: Patients had significantly higher respiratory scores than controls. AHI increased 4.6-fold (p = .006), RDI 2.5-fold (p = .008) and ODI 6.4-fold (p < .001). Oropharyngeal volumes showed a 30% decrease (p = .003). dB, TST and REM showed no significant differences. AHI (r = -.51; p = .005), ODI (r = -.60; p < .001) and RDI (r = -.45; p = .016) correlated negatively with pharyngeal volume. Wits appraisal correlated negatively with oropharyngeal volume (r = -.47; p = .010) and positively with AHI (r = .41; p = .03) and ODI (r = .49; p = .007). dB and TST (r = -.49; p = .008) and REM and RDI (r = -.43; p = .02) correlated negatively. UEQ-KPI (2.17 ± 0.24) confirmed excellent usability of PAT. CONCLUSION: Patients with mandibular retrognathia and abnormal sleep history showed significantly higher respiratory indices and smaller oropharyngeal volumes than neutrally configured controls. The dygnathia severity directly influenced the risk of obstructive sleep apnoea.

Prognostic factor identification by screening changes in differentially expressed genes in oral squamous cell carcinoma.

OBJECTIVE: This study was designed to identify changes in the expression of proteins occurring during the progression of oral squamous cell carcinoma (OSCC) and to validate their impact on patient prognosis. MATERIALS AND METHODS: The human OSCC cell line UPCI-SCC-040 was treated in vitro with TGF-ß1, and transcriptome analysis of differentially expressed genes (DEGs) revealed putative candidates relative to untreated cells. The respective protein expression levels of the most important genes were immunohistochemically validated on a tissue microarray (TMA) containing tissue samples from 39 patients with OSCC and were correlated with disease-free survival (DFS) as the primary clinical endpoint. RESULTS: Our univariate Cox proportional hazard regression (CR) analysis revealed significant correlations among positive N stage (local lymph node metastasis, p = .04), stearoyl-CoA desaturase-1 (p < .01), sclerostin (p = .01), and CD137L expression (p = .04) and DFS. Stearoyl-CoA desaturase-1 and sclerostin remained the main prognostic factors (p < .01) in the multiple CR model. CONCLUSION: We identified changes in differentially expressed genes during OSCC progression in vitro and translated the impact of the most deregulated genes on patient prognosis. Stearoyl-CoA desaturase-1 and sclerostin acted as independent prognostic factors in OSCC and could also be interesting candidates for new cancer targeted therapeutic approaches.

Is CCL2 an Important Mediator of Mast Cell-Tumor Cell Interactions in Oral Squamous Cell Carcinoma?

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.

Force delivery modification of removable thermoplastic appliances using Hilliard precision thermopliers for tipping an upper central incisor.

OBJECTIVES: To evaluate the force delivered by removable thermoplastic appliances (RTAs, aligners), altered with Hilliard precision thermopliers, on an upper central incisor to tip it in the palatal and vestibular directions. MATERIALS AND METHODS: A total of 10 aligners made from Ideal Clear® (polyethylene terephthalate glycol copolyester, PET-G) with a thickness of 1 mm were used in force analysis. Different-sized spot-thermoformed protuberances (bumps) were generated by activating the thermoplier (thin and thick) up to 30°, 60° and 90° in the centre of the palatal and vestibular surfaces of the aligner in 15° steps. The tipping (Fx) and intrusive (Fz) force components were measured on the isolated upper central incisor as part of a standardized resin model, with or without vertical loading by a weight equivalent. RESULTS: Thermoplier activation at 30°, 60° and 90° resulted in different bump heights. The analysis revealed significantly higher Fx and Fz values with increasing bump heights for every activation step in all cases (p < 0.0001, respectively). Overall, the values of the Fx force component were higher than those observed for Fz. Significant differences between the palatal and vestibular tipping procedures were found depending on the resulting force components when the thin thermoplier was used; in contrast, the thick thermoplier resulted in a larger dispersion of the force magnitudes. CONCLUSIONS: Aligners modified with Hilliard precision thermopliers showed altered biomechanical parameters. This approach could be an option for treatment modification. CLINICAL RELEVANCE: The instrumental examination provided informative results for daily practice, as activation, force dosage and different force values under chewing pressure can be estimated more precisely based on the determined force levels.

Time of day-dependent deviations in dynamic and static occlusion: A prospective clinical study.

STATEMENT OF PROBLEM: The registration of dental occlusion is essential for prosthodontic treatment. However, studies on time-dependent changes of static and dynamic occlusion that may affect definitive restorations are lacking. PURPOSE: The purpose of this prospective clinical study was to use conventional and digital occlusal registration techniques to evaluate time-dependent fluctuations in static and dynamic occlusion. MATERIAL AND METHODS: The static and dynamic occlusion of 19 healthy individuals (14 women and 5 men with a mean ±standard deviation age of 30.8 ±4.8 years) was examined 3 times a day using occlusal foil (12-µm occlusion foil) and a digital sensor (T-Scan III). The procedure was repeated after 14 days. The statistical analysis covered all registrations referencing the first measurement point to assess occurring differences, and changes per tooth and arch were determined (α=.05). Potential influencing factors were calculated by using mixed logistic regression. Marginal probabilities were calculated considering the registration technique and the time of measurement. RESULTS: Significant differences were found between registered occlusal patterns and the different registration techniques. Occlusal changes per maxillary dental arch were observed with static foil registration (P<.001; 98.8%), left laterotrusion foil registration (P=.001; 29.6%), right laterotrusion foil registration (P=.001; 29.6%), static sensor registration (P<.001; 20.3%), left laterotrusion sensor registration (P=.001; 71.7%), and right laterotrusion sensor registration (P=.005; 67.7%). None of the techniques showed higher probabilities of occlusal changes at a given time of day with respect to time-dependent changes. CONCLUSIONS: The study revealed that occlusion cannot be considered constant and that the topography and intensity of the contact points vary. Circadian occlusion variance can be assumed without preferring a specific time of the day. This differentiated view of occlusion as a changing system helps to clarify the challenge of dental restorations for both the patient and the practitioner.

Informational content of two-dimensional panoramic radiographs and lateral cephalometric radiographs with respect to the bone volume of intraoral donor regions considering CBCT imaging.

BACKGROUND: To test the hypothesis that cephalometric parameters in two-dimensional routine dental radiographs correlate with the bone volume of intraoral bone donor sites. METHODS: One-hundred and eight radiographs [36 panoramic radiographs (PRs), 36 lateral cephalometric radiographs (LCRs), and 36 cone-beam computed tomography scans (CBCT)] of 36 patients (all three imaging techniques applied according to the needs of treatment planning), were analyzed individually. Cephalometric parameters (PR and LCR) were correlated with the bone volume measurement in three-dimensional CBCT scans in three intraoral donor sites (chin, mandibular retromolar region, and zygomatic alveolar crest). RESULTS: The mean bone volumes measured for the chin were (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 (all p-values < 0.05) with the bone volume in the chin and the mandibular retromolar region. The bone volume of the zygomatic alveolar crest exhibited no correlations (p > 0.05) with cephalometric parameters. However, it was significantly correlated (p < 0.01) with the mandibular retromolar bone volume. No gender-specific differences (p > 0.05) were observed concerning bone volumes in all bone harvesting regions. Nevertheless, the male population's interforaminal distance in the chin region was significantly higher (p = 0.001). CONCLUSIONS: PRs and LCRs can be used at the initial stage of peri-implant augmentation planning to deduce conclusions about the bone volume in different intraoral bone donor sites. It can help describe indications and justify additional diagnostic options, such as three-dimensional radiologic techniques.

Increase of homogenous new bone formation using osteoinductive factor rhGDF-5 during sinus floor augmentation in Goettingen Minipigs.

OBJECTIVES: The aim of this study was to test the hypothesis that recombinant human growth and differentiation factor-5 (rhGDF-5) induces an increased and homogenous distribution of new bone formation across the entire volume of sinus floor augmentation in 12 Goettingen Minipigs. MATERIAL AND METHODS: In a randomized split-mouth design, one maxillary sinus was augmented with the bone substitute ß-TCP, whereas a combination of ß-TCP and the osteoinductive growth factor rhGDF-5 was used on the contralateral side. To evaluate the influence of dose and time on the effectiveness of the factor, two different concentrations of rhGDF-5 (400 µg and 800 µg) and healing periods (4 and 12 weeks) were each analysed. RESULTS: After 4 weeks, a homogenous gradient of bone formation could be observed for all dosage groups, with decreasing bone density from the local bone towards the sinus membrane. Both test groups, however, achieved a higher total level of bone formation compared with the control group, which was only significant in the low-dose group (P = 0.0184). After 12 weeks, the influence of the growth factor significantly depends on the region (P = 0.023). In the low-dose group, the new bone formation did not differ significantly within the examined regions of the graft (P = 0.1118), suggesting a homogeneous bone formation over the entire augmentation. The gradient of the high-dose group was similar to the control group with a decrease of local bone development. CONCLUSIONS: rhGDF-5 delivered on a ß-TCP scaffold material leads to an increase in homogeneous new bone formation across the entire volume of the sinus floor augmentation.

Influence of synthetic polyethylene glycol hydrogels on new bone formation during mandibular augmentation procedures in Goettingen minipigs.

Polyethylene glycol hydrogels (PEG) have been used as slow release carrier for osteoinductive growth factors in order to achieve a retarded delivery. However, there have been concerns about negative effects on bone regeneration. This study aims to test whether PEG hydrogels themselves affect new bone formation (NBF), when used as a carrier during mandibular augmentation procedures. In a randomized split-mouth design, bilateral mandibular bone defects were surgically created in 12 Goettingen minipigs, and subsequently augmented, using PEG hydrogel on one side of the mandible. The contralateral sides, without PEG, served as controls. After 4 and 12 weeks, bone formation was evaluated in six animals each. A comparison of the data, using a three-way analysis of variance (ANOVA), revealed a significant effect of the healing time and the region of the graft on the distribution and enhancement of NBF (P < .0001, respectively). Although a 0.3% (95%-CI [-5.5; 4.8]) lower volume density of newly formed bone could be observed over all PEG hydrogel sections, in contrast to the contralateral controls, the analysis revealed no clinically significant effects of the PEG hydrogel treatment on the total level (P = 0.90), and the distribution of NBF (P = 0.54). In conclusion, PEG hydrogels do not affect NBF when used as a carrier for osteoinductive growth factors during mandibular augmentation procedures.

EMMPRIN promotes spheroid organization and metastatic formation: comparison between monolayers and spheroids of CT26 colon carcinoma cells.

Background: In vitro studies often use two-dimensional (2D) monolayers, but 3D cell organization, such as in spheroids, better mimics the complexity of solid tumors. To metastasize, cancer cells undergo the process of epithelial-to-mesenchymal transition (EMT) to become more invasive and pro-angiogenic, with expression of both epithelial and mesenchymal markers. Aims: We asked whether EMMPRIN/CD147 contributes to the formation of the 3D spheroid structure, and whether spheroids, which are often used to study proliferation and drug resistance, could better model the EMT process and the metastatic properties of cells, and improve our understanding of the role of EMMPRIN in them. Methods: We used the parental mouse CT26 colon carcinoma (CT26-WT) cells, and infected them with a lentivirus vector to knock down EMMPRIN expression (CT26-KD cells), or with an empty lentivirus vector (CT26-NC) that served as a negative control. In some cases, we repeated the experiments with the 4T1 or LLC cell lines. We compared the magnitude of change between CT26-KD and CT26-WT/NC cells in different metastatic properties in cells seeded as monolayers or as spheroids formed by the scaffold-free liquid overlay method. Results: We show that reduced EMMPRIN expression changed the morphology of cells and their spatial organization in both 2D and 3D models. The 3D models more clearly demonstrated how reduced EMMPRIN expression inhibited proliferation and the angiogenic potential, while it enhanced drug resistance, invasiveness, and EMT status, and moreover it enhanced cell dormancy and prevented CT26-KD cells from forming metastatic-like lesions when seeded on basement membrane extract (BME). Most interestingly, this approach enabled us to identify that EMMPRIN and miR-146a-5p form a negative feedback loop, thus identifying a key mechanism for EMMPRIN activities. These results underline EMMPRIN role as a gatekeeper that prevents dormancy, and suggest that EMMPRIN links EMT characteristics to the process of spheroid formation. Conclusions: Thus, 3D models can help identify mechanisms by which EMMPRIN facilitates tumor and metastasis progression, which might render EMMPRIN as a promising target for anti-metastatic tumor therapy.

How to register static occlusion - Correlation of contemporary techniques.

Statement of problem: A working knowledge of the analytical capacities of contemporary registration methods is essential for prosthetic treatment; however, there is a paucity of studies which coherently investigate the capabilities and limitations of the various diagnostic procedures utilized for prosthetic occlusion. Purpose: The present prospective clinical study aimed to evaluate the similarities and differences among contemporary registration methods through comparative analysis. Material and methods: The habitual static occlusion of 19 healthy individuals (14 women; mean age ± standard deviation, 30.8 ± 4.8 years) was analyzed 3 times a day, using shimstock foil, occlusal foil, wax registration, silicone registration, and computerized registration. The procedures were repeated after 14 days. Statistical analyses included all registrations referencing the first measurement point to assess the mean values of antagonistic contacts and the differences between these measurements. Pearson's and Kendall's correlation analyses were performed as part of the coherent mixed logistic regression model, and marginal probabilities were calculated using the registration technique and repeated measurements. Results: Strong correlations were found among the various registration techniques. The largest effect sizes were observed among the wax, silicone, occlusion foil, and computerized registrations (r = 0.95, P < 0.001 to r = 0.62, P < 0.001), while the lowest effect sizes were found for shimstock correlations (τ = 0.41, P < 0.001 to τ = 0.27, P < 0.001). Occlusal changes per maxillary arch were observed referencing the first measurement time with wax registration (P < 0.001; 7.4%), shimstock foil (P < 0.001; 13.8%), computerized registration (P < 0.001; 20.3%), silicone registration (P = 0.009; 66.3%), and occlusion foil (P < 0.001; 98.8%). Occlusal changes per maxillary tooth were observed from the first incisor (P < 0.001; 5.7%) to the third molar (P < 0.001; 18.1%). Conclusions: The results of the present study revealed that there are strong overall correlations among the various contemporary registration techniques. The different affinities of the techniques used to register occlusal changes, however, showed differences in the measurement techniques, which should be neither over- nor underestimated. The differential tendencies of teeth to change should be considered, even if a hypervariable system is assumed.

In-house virtual surgical planning and guided mandibular reconstruction is less precise, but more economical and time-efficient than commercial procedures.

BACKGROUND: To compare an in-house and a commercially available surgical planning solution for mandibular reconstruction in terms of postoperative reconstruction accuracy and economic benefit. METHODS: Twenty-nine consecutive patients with advanced oral squamous cell carcinoma (OSCC) requiring segmental mandibular reconstruction were enrolled. Fifteen patients underwent in-house surgical planning and 14 patients underwent a commercially available planning solution. A morphometric comparison of preoperative and postoperative computed tomography (CT) data sets and a cost-benefit comparison were performed. RESULTS: Volumes of planned and reconstructed bone segments differed significantly for both in-house planning (p = 0.0431) and commercial planning (p < 0.0001). Significant differences in osteotomy angles were demonstrated for in-house planning (p = 0.0391). Commercial planning was superior to in-house planning for total mandibular deviation (p = 0.0217), intersegmental space volumes (p = 0.0035), and lengths (p = 0.0007). No significant difference was found between the two planning solutions in terms of intersegmental ossification and the incidence of wound healing disorders. In-house planning took less time than commercial planning (p < 0.0001). Component manufacturing costs (p < 0.0001) and total cumulative costs (p < 0.0001) were significantly lower for in-house planning. CONCLUSIONS: In-house surgical planning is less accurate but has a cost advantage and could be performed in less time.

Sclerostin Alters Tumor Cell Characteristics of Oral Squamous Cell Carcinoma and May Be a Key Player in Local Bone Invasion.

Localized jawbone invasion is a milestone in the progression of oral squamous cell carcinoma (OSCC). The factors that promote this process are not well understood. Sclerostin is known to be involved in bone metabolism and there are preliminary reports of its involvement in bone tumors and bone metastasis. To identify a possible involvement of sclerostin in the bone invasion process of OSCC, sclerostin expression was analyzed in vitro in two different human OSCC tumor cell lines by quantitative real-time polymerase chain reaction (qRT-PCR), and the effect of recombinant human (rh)-sclerostin treatment on tumor cell capabilities was evaluated using proliferation, migration, and invasion assays. Undifferentiated human mesenchymal stem cells (hMSCs) were osteogenically differentiated and co-cultured with OSCC tumor cells to demonstrate potential interactions and migration characteristics. Sclerostin expression was evaluated in clinical cases by immunohistochemistry at the OSCC-jawbone interface in a cohort of 15 patients. Sclerostin expression was detected in both OSCC tumor cell lines in vitro and was also detected at the OSCC-jawbone interface in clinical cases. Tumor cell proliferation rate, migration and invasion ability were increased by rh-sclerostin treatment. The migration rate of tumor cells co-cultured with osteogenically differentiated hMSCs was increased. The results presented are the first data suggesting a possible involvement of sclerostin in the bone invasion process of OSCC, which deserves further investigation and may be a potential approach for drug-based tumor therapy.

Improvement of Quality of Life after Surgical Treatment of Patients with MRONJ: A Prospective Analysis Using the SF-12 and OHIP-14 Questionnaires.

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a rare, serious, and debilitating disease of unknown cause that can be associated with significant health-related quality of life (HRQOL) impairment. Hematological disease is characterized by a nonhealing exposed jawbone in patients with a history of antiresorptive or antiangiogenic agent use without radiation exposure to the head or neck. Patients and Materials and Methods. This prospective study over the period from May 2020 to December 2021 included a representative sample consisting of 27 patients with at least stage 2 MRONJ lesions who underwent surgical rehabilitation via oral and maxillofacial surgery at the University Medical Center Göttingen, Germany. Quality of life data were collected over a 6-month postoperative period using the Health-Related QOL (SF-12) and Oral Health-Related QOL (OHIP-14) questionnaires. Results: A total of 27 patients considered in the study had a total of 42 MRONJ lesions, corresponding to a mean of 1.56 necroses per patient. MRONJ lesions were downstaged in 85% of the patients. HRQOL was evaluated with the SF-12 questionnaire. Significant improvements were found in six of the eight categories (General Health (p < 0.001), Bodily Pain (p < 0.001), Mental Health (p < 0.001), Vitality (p < 0.001), Role-Emotional (p=0.028), and Social Functioning (p=0.031)). The OHRQOL score also improved significantly after surgical intervention (p < 0.001). Conclusion: With completed surgical therapy, improvements in HRQOL and OHRQOL are measurable.

The Role of Augmented Reality in the Advancement of Minimally Invasive Surgery Procedures: A Scoping Review.

The purpose of this review was to analyze the evidence on the role of augmented reality (AR) in the improvement of minimally invasive surgical (MIS) procedures. A scoping literature search of the PubMed and ScienceDirect databases was performed to identify articles published in the last five years that addressed the direct impact of AR technology on MIS procedures or that addressed an area of education or clinical care that could potentially be used for MIS development. A total of 359 studies were screened and 31 articles were reviewed in depth and categorized into three main groups: Navigation, education and training, and user-environment interfaces. A comparison of studies within the different application groups showed that AR technology can be useful in various disciplines to advance the development of MIS. Although AR-guided navigation systems do not yet offer a precision advantage, benefits include improved ergonomics and visualization, as well as reduced surgical time and blood loss. Benefits can also be seen in improved education and training conditions and improved user-environment interfaces that can indirectly influence MIS procedures. However, there are still technical challenges that need to be addressed to demonstrate added value to patient care and should be evaluated in clinical trials with sufficient patient numbers or even in systematic reviews or meta-analyses.

Knocking-Down CD147/EMMPRIN Expression in CT26 Colon Carcinoma Forces the Cells into Cellular and Angiogenic Dormancy That Can Be Reversed by Interactions with Macrophages.

Metastasis in colorectal cancer is responsible for most of the cancer-related deaths. For metastasis to occur, tumor cells must first undergo the epithelial-to-mesenchymal transition (EMT), which is driven by the transcription factors (EMT-TFs) Snail, Slug twist1, or Zeb1, to promote their migration. In the distant organs, tumor cells may become dormant for years, until signals from their microenvironment trigger and promote their outgrowth. Here we asked whether CD147/EMMPRIN controls entry and exit from dormancy in the aggressive and proliferative (i.e., non-dormant) CT26 mouse colon carcinoma cells, in its wild-type form (CT26-WT cells). To this end, we knocked down EMMPRIN expression in CT26 cells (CT26-KD), and compared their EMT and cellular dormancy status (e.g., proliferation, pERK/pP38 ratio, vimentin expression, expression of EMT-TFs and dormancy markers), and angiogenic dormancy (e.g., VEGF and MMP-9 secretion, healing of the wounded bEND3 mouse endothelial cells), to the parental cells (CT26-WT). We show that knocking-down EMMPRIN expression reduced the pERK/pP38 ratio, enhanced the expression of vimentin, the EMT-TFs and the dormancy markers, and reduced the proliferation and angiogenic potential, cumulatively indicating that cells were pushed towards dormancy. When macrophages were co-cultured with both types of CT26 cells, the CT26-WT cells increased their angiogenic potential, but did not change their proliferation, state of EMT, or dormancy, whereas the CT26-KD cells exhibited values mostly similar to those of the co-cultured CT26-WT cells. Addition of recombinant TGFß or EMMPRIN that simulated the presence of macrophages yielded similar results. Combinations of low concentrations of TGFß and EMMPRIN had a minimal additive effect only in the CT26-KD cells, suggesting that they work along the same signaling pathway. We conclude that EMMPRIN is important as a gatekeeper that prevents cells from entering a dormant state, and that macrophages can promote an exit from dormancy.

The Proteomes of Oral Cells Change during Co-Cultivation with Aggregatibacter actinomycetemcomitans and Eikenella corrodens.

BACKGROUND: Changes in the proteome of oral cells during periodontitis have rarely been investigated. This lack of information is partially attributed to the lack of human cell lines derived from the oral cavity for in vitro research. The objective of the present study was to create cell lines from relevant oral tissues and compare protein expression in cells cultured alone and in cells co-cultivated with periodontitis-associated bacterial strains. METHODS: We established human cell lines of gingival keratinocytes, osteoblastic lineage cells from the alveolar bone, periodontal ligament fibroblasts, and cementum cells. Using state-of-the-art label-free mass spectrometry, we investigated changes in the proteomes of these cells after co-cultivation with Aggregatibacter actinomycetemcomitans and Eikenella corrodens for 48 h. RESULTS: Gingival keratinocytes, representing ectodermal cells, exhibited decreased expression of specific keratins, basement membrane components, and cell-cell contact proteins after cultivation with the bacterial strains. Mesodermal lineage cells generally exhibited similar proteomes after co-cultivation with bacteria; in particular, collagens and integrins were expressed at higher levels. CONCLUSIONS: The results of the present study will help us elucidate the cellular mechanisms of periodontitis. Although co-cultivation with two periodontitis-associated bacterial strains significantly altered the proteomes of oral cells, future research is needed to examine the effects of complex biofilms mimicking in vivo conditions.

24/7 Therapeutic Drug Monitoring of Beta-Lactam Antibiotics with CLAM-2000.

BACKGROUND: The aim of this study was to evaluate the CLAM-2000 automated preanalytical sample preparation module with integrated liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) as a method for 24/7 therapeutic drug monitoring (TDM) of beta-lactam antibiotics in routine clinical diagnostics. METHODS: Method validation was performed using quality control samples. Method comparison was performed with routine samples from patients treated with beta-lactam antibiotics. RESULTS: The determination of piperacillin, meropenem, ceftazidime, flucloxacillin, and cefotaxime was performed using D5-piperacillin and D6-meropenem as internal standards. The linearity of the method was within the therapeutic range of beta-lactam antibiotics. The imprecision and accuracy data obtained from quality control samples were within 15%, and the imprecision of patient samples on the instrument was less than the 5% coefficient of variation (CV). Internal standards stored in the instrument at 9 °C for at least one week were stable, which facilitated reagent use and storage. CONCLUSION: The CLAM-2000 (Shimadzu, Kyoto, Japan) provides reproducible results as an established routine instrument and is a useful tool for 24/7 TDM of beta-lactam antibiotics in routine clinical diagnostics.

Evaluation of occlusal function during orthognathic therapy : A prospective clinical trial using a digital registration method.

OBJECTIVES: 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. METHODS: 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 T­Scan Novus (Tekscan, South Boston, MA, USA) application. RESULTS: 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). CONCLUSIONS: 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. CLINICAL RELEVANCE: Severe malocclusion leads to a significantly lower masticatory performance for patients, which can be improved by orthognathic therapy and captured by digital occlusal registration.

Postoperative facial appearance of patients with extensive oral squamous cell carcinoma can be adequately preserved with in­house virtually planned mandibular reconstruction.

The present study aimed to assess the concordance of preoperative and postoperative hard and soft tissues in patients with advanced oral squamous cell carcinoma (OSCC) following virtual surgical planning (VSP) mandibular reconstruction. In the present study, a cohort of 32 patients with OSCC underwent in-house VSP, followed by guided mandibular reconstruction utilizing vascularized free tissue grafts sourced from the fibula or scapula. A morphometric analysis was conducted comparing preoperative and postoperative three-dimensional virtual models to evaluate discrepancies and identify potential risk factors associated with poor reconstruction outcomes. The outcome variables were the differences in root mean square (RMS) and mean surface distance (MSD) resulting from the application of an iterative closest point algorithm to the virtual data. The validity of soft tissue comparison data is limited due to its susceptibility to various confounding variables. The present study conducted a comprehensive re-evaluation of these variables. High tumor stage, positive N status and the use of adjuvant therapy contributed to more noticeable differences in preoperative and postoperative facial soft tissue appearance. The accuracy of postoperative bone reconstruction results was higher in patients who underwent neomandibular formation using a fibular graft compared with those who received a scapular graft. Preoperative and postoperative soft tissue analyses were conducted for comparison. The MSD showed a deviation of 3.2 mm (± 2.0 mm SD; range 1.3-9.5 mm), whereas the RMS was 5.3 (± 2.9 SD; range 2.1-14). In conclusion, in-house VSP and guided mandibular reconstructions can yield clinically accurate results, preserving patient appearance and offering the advantage of rapid feasibility.