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Abstract The CARLO (cold ablation robot-guided laser osteotome) is a compact device with integrated multiple sensory, steering and safety checking elements. A multi-center study was performed to evaluate the CARLO device for the linear part of midface osteotomy in 28 patients. Feasibility, success rate, safety, performance and experience of the surgeons were assessed and evaluated. All 28 procedures were completed with CARLO without falling back to the conventional methods, giving a technical success rate of 100%. For 27 (96%) cases, procedural success was achieved with cutting lines deviation less than 2 mm. For 25 procedures, the CARLO-cutting was conducted smoothly. In the other 3 cases, some minor difficulties related to the reference markers were reported. For 18 procedures, no change for the cutting path was necessary. For the other 10 cases, cut path was adapted. Intraoperative re-planning was possible, easy and quick without significant delay of the procedures. No CARLO-related adverse events were recorded. Especially, there was no unexpected and unusual bleeding during the CARLO-conducted osteotomy. The time needed for the registration ranged from 1 to 12 min (median = 4). The CARLO-cutting lasted for 5 to 21 min (median = 7). The present study demonstrated feasibility, simplicity, safety, reliability and accuracy of CARLO for the linear part of midface osteotomy.

Abstract Background Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignancy worldwide, with high incidence and poor survival rates. RBP1 is highly expressed in several kinds of cancer and plays a potential prognostic factor. However, the relationship between RBP1 and HNSCC were analyzed based on The Cancer Genome Atlas (TCGA) database. Materials and methods RBP1 expression and clinical information were obtained from the Cancer Genome Atlas (TCGA) database. Tumor tissue and adjacent normal tissue of 6 HNSCC patients were collected to analyze the RBP1 mRNA expression level by quantitative PCR. Cox regression analysis was used to evaluate the prognostic values of RBP1 and clinical data in HNSCC. A nomogram was also established to predict the impact of RBP1 on prognosis based on Cox multivariate results. The methylation level of RBP1 in HNSC and its prognosis were analyzed in UALACN and MethSurv. Finally, the potential biological functions of RBP1 were investigated using gene set enrichment analysis (GSEA) and single sample GSEA (ssGSEA). Results The mRNA expression levels of RBP1 were highly expressed in HNSCC tissue. The Cox analyses demonstrate that highly-expressed RBP1 is an independent prognosis marker(P

IntroductionHead and neck cancer (HNC) is a complex disease, and multiple risk factors can lead to its progression. Observational studies indicated that herpes simplex virus (HSV) may be correlated with the risk of HNC. However, the causal effects and direction between them were still unclear.MethodsThis study utilized a Mendelian randomization (MR) approach for causality assessment between HSV infection and Head and neck cancer based on the latest public health data and Genome-Wide Association Study (GWAS) data. The causal effects were estimated using IVW, weighted median, and MR-Egger. A reverse MR analysis was subsequently performed. Cochrans Q test, MR‐Egger intercept test, leave one out analysis, and the funnel plot were all used in sensitivity analyses.ResultsGenetically predicted higher level of HSV-1 IgG was causally related to HNC (OR=1.0019, 95%CI=1.0003–1.0036, p=0.0186, IVW) and oral and oropharyngeal cancer (OR=1.0018, 95%CI=1.0004–1.0033, p=0.0105, IVW). The reverse MR analysis did not demonstrate a reverse causal relationship between HSV and HNC. However, HSV-2 infection was not causally related to HNC data and oropharyngeal cancer data. Sensitivity analysis was performed and revealed no heterogeneity and horizontal pleiotropy.ConclusionCollectively, a significant association was noted between HSV infection and increased risk of HNC, providing valuable insights into the etiology of this malignancy. Further in-depth study is needed to validate these findings and elucidate the underpinning mechanisms.

Abstract Bioactive material concepts for targeted therapy have been an important research focus in regenerative medicine for years. The aim of this study was to investigate a proof-of-concept composite structure in the form of a membrane made of natural silk fibroin (SF) and extracellular vesicles (EVs) from gingival fibroblasts. EVs have multiple abilities to act on their target cell and can thus play crucial roles in both physiology and regeneration. This study used pH neutral, degradable SF-based membranes, which have excellent cell- and tissue-specific properties, as the carrier material. The characterization of the vesicles showed a size range between 120 and 180 nm and a high expression of the usual EV markers (e.g. CD9, CD63 and CD81), measured by nanoparticle tracking analysis (NTA) and single-EV flow analysis (IFCM). An initial integration of the EVs into the membrane was analyzed using scanning and transmission electron microscopy (SEM and TEM) and vesicles were successfully detected, even if they were not homogeneously distributed in the membrane. Using direct and indirect tests, the cytocompatibility of the membranes with and without EVs could be proven and showed significant differences compared to the toxic control (p 0.05).

Abstract Purpose Post-interventional hemorrhage can result in serious complications, especially in patients with hemostatic disorders. Identification of safe and efficient local hemostatic agents is important, particularly in the context of an ageing society and the emergence of new oral anticoagulants. The aim of this in vitro study was to investigate the potential of silk fibroin membranes coated with the inorganic polymer polyphosphate (polyP) as a novel hemostatic device in oral surgery. Methods Cocoons of the silkworm Bombyx mori were degummed and dissolved. Varying amounts of long-chain polyP (2–2000 µg/mm2) were adsorbed to the surface of silk fibroin membranes. Analysis of the procoagulant effect of polyP-coated silk membranes was performed using real-time thrombin generation assays in human plasma. Increasing concentrations of polyP (0.15–500 µg/ml) served as a positive control, while uncoated silk fibroin membranes were used as negative control. Results PolyP-coated silk fibroin membranes triggered coagulation when compared to plasma samples and pure silk fibroin membranes. A polyP-dose-dependent effect of thrombin generation could be found with a maximum (ETP = 1525.7 nM⋅min, peak thrombin = 310.1 nM, time to peak = 9.8 min, lag time = 7.6 min.) at 200 µg/mm2 of polymer loading on the silk fibroin membrane surface. Conclusions In this study, it was demonstrated that silk fibroin membranes coated with polyP have the potential to act as a promising novel hemostatic device. Graphical Abstract

Abstract Background Various data have been obtained on the relationship between body mass index (BMI) and C-reactive protein (CRP) and periodontitis. The aim of this study was to determine whether CRP/BMI are associated with periodontitis using data from the National Health and Nutrition Examination Survey (NHANES) database. Methods A cross-sectional analysis of data from 3602 participants in the 2009–2010 NHANES cycle was performed. The definition of periodontitis was used to divide participants into four groups according to the criteria of Eke. Correlations between CRP/BMI and periodontitis were tested for statistical significance by means of descriptive statistics, multivariate regression, and subgroup-stratified analyses, with and without adjustments for confounders (such as age and sex). Results There were no statistically significant differences (p > 0.05) regarding BMI and the development of periodontitis. After adjustment for age, sex, race, marital status, annual family income, alcohol consumption, hypertension, smoking, chronic pulmonary disease, cardiovascular disease, diabetes, flossing, and arthritis, CRP correlated significantly with the development of periodontitis in the subgroups stratified by obesity, with an odds ratio (OR) of 1.2 (95% CI, 1.0 to 1.5). Conclusion Through data analysis, we found an association between CRP levels and periodontitis prevalence in the American population, although this association was only present in the obese population. While there are several hypotheses about the underlying mechanism, further studies are needed to validate these findings.

Abstract Purpose The macrogeometry of a dental implant plays a decisive role in its primary stability. A larger diameter, a conical shape, and a roughened surface increase the contact area of the implant with the surrounding bone and thus improve primary stability. This is considered the basis for successful implant osseointegration that different factors, such as implant design, can influence. This narrative review aims to critically review macro-geometric features affecting the primary stability of dental implants. Methods For this review, a comprehensive literature search and review of relevant studies was conducted based on formulating a research question, searching the literature using keywords and electronic databases such as PubMed, Embase, and Cochrane Library to search for relevant studies. These studies were screened and selected, the study quality was assessed, data were extracted, the results were summarized, and conclusions were drawn. Results The macrogeometry of a dental implant includes its surface characteristics, size, and shape, all of which play a critical role in its primary stability. At the time of placement, the initial stability of an implant is determined by its contact area with the surrounding bone. Larger diameter and a conical shape of an implant result in a larger contact area and better primary stability. But the linear relationship between implant length and primary stability ends at 12 mm. Conclusions Several factors must be considered when choosing the ideal implant geometry, including local factors such as the condition of the bone and soft tissues at the implant site and systemic and patient-specific factors such as osteoporosis, diabetes, or autoimmune diseases. These factors can affect the success of the implant procedure and the long-term stability of an implant. By considering these factors, the surgeon can ensure the greatest possible therapeutic success and minimize the risk of implant failure. Graphical Abstract

In Neurofibromatosis type 1 (NF1), peripheral nerve sheaths tumors are common, with cutaneous neurofibromas resulting in significant aesthetic, painful and functional problems requiring surgical removal. To date, determination of adequate surgical resection margins-complete tumor removal while attempting to preserve viable tissue-remains largely subjective. Thus, residual tumor extension beyond surgical margins or recurrence of the disease may frequently be observed. Here, we introduce Shifted-Excitation Raman Spectroscopy in combination with deep neural networks for the future perspective of objective, real-time diagnosis, and guided surgical ablation. The obtained results are validated through established histological methods. In this study, we evaluated the discrimination between cutaneous neurofibroma (n = 9) and adjacent physiological tissues (n = 25) in 34 surgical pathological specimens ex vivo at a total of 82 distinct measurement loci. Based on a convolutional neural network (U-Net), the mean raw Raman spectra (n = 8,200) were processed and refined, and afterwards the spectral peaks were assigned to their respective molecular origin. Principal component and linear discriminant analysis was used to discriminate cutaneous neurofibromas from physiological tissues with a sensitivity of 100%, specificity of 97.3%, and overall classification accuracy of 97.6%. The results enable the presented optical, non-invasive technique in combination with artificial intelligence as a promising candidate to ameliorate both, diagnosis and treatment of patients affected by cutaneous neurofibroma and NF1.

IntroductionThe coronavirus disease 2019 (COVID-19) has emerged as a main global public health challenge. Additionally, herpes simplex virus type-1 (HSV-1) and type 2 (HSV-2) are widespread viruses that can cause orolabial herpes and genital herpes. Several clinical case reports have declared a possible association between the two, however, the causal relationship between them has not been clarified.MethodsThis study utilized a Mendelian randomization (MR) approach for causality assessment between COVID-19 infection and HSV infection based on the latest public health data and Genome-Wide Association Study (GWAS) data. Multiple causal estimation methods, such as IVW, weighted median, simple mode, and weighted mode, were employed to validate the causal relation between COVID-19 infection and HSV infection, with COVID-19 infection, COVID-19 hospitalization, and severe COVID-19 as exposures, and HSV1/2 infection as the outcome. A reverse MR analysis was subsequently performed.ResultsMR analysis exhibited that COVID-19 infection was relevant to a reduced risk of HSV1 infection (p=7.603239e−152, OR=0.5690, 95%CI=0.5455−0.5935, IVW). Regarding the effect of COVID-19 infection on HSV2, MR analysis suggested that COVID-19 infection was correlated with an augmented risk of HSV2 infection (p=6.46735e−11, OR=1.1137, 95%CI=1.0782−1.1502, IVW). The reverse MR analysis did not demonstrate a reverse causal relationship between HSV and COVID-19. DiscussionAltogether, COVID-19 infection might cause a decreased risk of HSV1 infection and an elevated risk of HSV2 infection.

Introduction: Stem cells and scaffolds are an important foundation and starting point for tissue engineering. Human dental pulp stem cells (DPSC) are mesenchymal stem cells with self-renewal and multi-directional differentiation potential, and are ideal candidates for tissue engineering due to their excellent biological properties and accessibility without causing major trauma at the donor site. Tetracycline hydrochloride (TCH), a broad-spectrum antibiotic, has been widely used in recent years for the synthesis of cellular scaffolds to reduce the incidence of postoperative infections.Methods: In order to evaluate the effects of TCH on DPSC, the metabolism of DPSC in different concentrations of TCH environment was tested. Moreover, cell morphology, survival rates, proliferation rates, cell migration rates and differentiation abilities of DPSC at TCH concentrations of 0–500 μg/ml were measured. Phalloidin staining, live-dead staining, MTS assay, cell scratch assay and real-time PCR techniques were used to detect the changes in DPSC under varies TCH concentrations.Results: At TCH concentrations higher than 250 μg/ml, DPSC cells were sequestered, the proportion of dead cells increased, and the cell proliferation capacity and cell migration capacity decreased. The osteogenic and adipogenic differentiation abilities of DPSC, however, were already inhibited at TCH con-centrations higher than 50 μg/ml. Here, the expression of the osteogenic genes, runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN), the lipogenic genes lipase (LPL), as well as the peroxisome proliferator-activated receptor-γ (PPAR-γ) expression were found to be down-regulated.Discussion: The results of the study indicated that TCH in concentrations above 50 µg/ml negatively affects the differentiation capability of DPSC. In addition, TCH at concentrations above 250 µg/ml adversely affects the growth status, percentage of living cells, proliferation and migration ability of cells.

PurposeSeveral existing studies have revealed that the occurrence of lichen planus (LP) is relevant to the gut microbiota, and the causal relationship between gut microbiota and LP was analyzed using the Mendelian randomization (MR) method.MethodsThrough the two-sample MR method, single nucleotide polymorphisms (SNPs) relevant to gut microbiota were selected as instrument variables (IVs) to evaluate the causal association between gut microbiota and the risk of LP.ResultsAccording to the selection criteria of inverse-variance weighted (IVW), six bacterial genera were found to be significantly linked to the initiation of LP; The IVW results suggested that Oxalobacteraceae, Victivallaceae, and Actinobacteria could restrain the initiation of LP, showing protective effects against LP. Desulfovibrio, Veillonella, and Ruminococcus gauvreauii groups were demonstrated to have casual correlations with the onset of LP.ConclusionThe relationship between gut microbiota and LP was not a single positive or inverse relationship. Investigation of the causal relationship of these gut microbiota with LP could further provide evidence for the intestine-skin axis theory. However, the specific mechanism of microorganisms affecting the skin remains to be clarified. In this paper, the protective effects and mechanisms of Oxalobacteraceae, Victivallaceae, and Actinobacteria on LP require further exploration.

Abstract Aim Aim of this study was to investigate the association between periodontitis and arterial hypertension, both of which show correlations with classical cardiovascular risk factors and inflammatory activity. Materials and methods A cross-sectional analysis of data from a large population-based health survey (the Hamburg City Health Study, HCHS) including 5934 participants with complete periodontal examination and blood pressure data, of whom 5735 had medical records regarding anti-hypertensive medication, was performed. Probing depths, gingival recessions, bleeding on probing (BOP), dental plaque, and decayed-missing-filled teeth (DMFT) indices were recorded as measures of oral health. Clinical attachment loss (CAL) per tooth was calculated and periodontitis was staged into three groups (no/mild, moderate, severe). Arterial hypertension was diagnosed based on the participants’ medication history and systolic and diastolic blood pressure values. Logistic regression models were constructed accounting for a set of potential confounders (age, sex, smoking, body mass index (BMI), diabetes, educational level, alcohol intake) and high sensitivity-C-reactive protein (hsCRP). Results The odds of arterial hypertension increased significantly along with periodontitis severity (OR for severe periodontitis: 2.19; 95% CI 1.85–2.59; p

We present the case of a 53-year-old woman who was diagnosed with early-stage lung cancer by targeted cancer screening consisting of an immunological biopsy-based blood test followed by radiological imaging. The PanTum Detect blood test detects the biomarkers Apo10/DNaseX and Transketolase-like 1 (TKTL1) in circulating macrophage-like cells from peripheral blood samples to identify asymptomatic individuals with a high risk for malignancy. The elevated blood test values initiated an 18F-FDG PET/CT visualization for further clarification. In this case, imaging indicated a lung carcinoma in the right upper lobe. A biopsy confirmed the presence of a lung carcinoma, which was removed surgically. Histologic examination revealed a typical I A2 carcinoid, which was completely removed, making further therapy obsolete.

Abstract Background There is limited evidence for the use of zirconium dioxide implants in immediate implant placement as well as for related immediate loading protocols. The aim of this retrospective study was to investigate the survival rate, success and patient satisfaction of immediately placed zirconia implants compared to delayed placed implants. Methods The study included 58 partially edentulous patients who were treated between 2013 and 2015 with immediate and delayed transgingival healing zirconium dioxide implants (SDS, Kreuzlingen/ Switzerland). In addition to survival and success rate, marginal bone loss was assessed using radiographs and soft tissue was evaluated using Pink Esthetic Score. Oral health-related quality of life was investigated prospectively using a modified OHIP questionnaire. Results The cumulative survival rate of all implants included was 92% with 88% classified as full success. No significant difference was found between the bone levels of immediately and delayed placed and immediately and delayed loaded implants. The mean Pink Esthetic Score after final prosthetic rehabilitation was 12.2/14 points indicating excellent esthetic clinical results. Analysis of the OHIP questionnaire showed a mean value of 0.54/100 points reflecting a high patient satisfaction. Conclusions Immediate and delayed placed as well as loaded zirconium dioxide implants showed excellent results regarding implant success and survival in this study. Zirconium dioxide implants may ensure excellent esthetic results and high patient satisfaction.

Abstract Purpose Placement of dental implants has evolved to be an advantageous treatment option for rehabilitation of the fully or partially edentulous mandible. In case of extensive horizontal bone resorption, the bone volume needs to be augmented prior to or during implant placement in order to obtain dental rehabilitation and maximize implant survival and success. Methods Our aim was to systematically review the available data on lateral augmentation techniques in the horizontally compromised mandible considering all grafting protocols using xenogeneic, synthetic, or allogeneic material. A computerized and manual literature search was performed for clinical studies (published January 1995 to March 2021). Results Eight studies ultimately met the inclusion criteria comprising a total of 276 procedures of xenogeneic, allogeneic, or autogenous bone graft applications in horizontal ridge defects. Particulate materials as well as bone blocks were used as grafts with a mean follow-up of 26.0 months across all included studies. Outcome measures, approaches and materials varied from study to study. A gain of horizontal bone width of the mandible with a mean of 4.8 mm was observed in seven of eight studies. All but one study, reported low bone graft failure rates of 4.4% in average. Conclusions Only limited data are available on the impact of different horizontal augmentation strategies in the mandible. The results show outcomes for xenogeneic as well as autologous bone materials for horizontal ridge augmentation of the lower jaw. The use of allogeneic bone-block grafts in combination with resorbable barrier membranes must be re-evaluated. Randomized controlled clinical trials are largely missing.

Aims. By measuring the extent of cytokines secreted by human dental pulp stem cells (hDPSCs) from passages 2 through 10, the optimal passage of hDPSCs was determined. This offers a potential theoretical basis for the treatment of neurological disorders. Method. After isolation and culture of hDPSCs from human teeth, the morphological features of the cells were observed under an inverted microscope. hDPSCs were identified by their immunophenotypes and their multiple differentiation capability. Cytokine concentrations secreted in the supernatants at passages 2-10 were detected by ELISA. Results. hDPSCs were viewed as fusiform or polygonal in shape, with a bulging cell body, homogenized cytoplasm, and a clear nucleus. Moreover, they could differentiate into neuroblasts in vitro. hDPSCs at passage 3 were positive for CD29 (91.5%), CD73 (94.8%) and CD90 (96.7%), but negative for the hematopoietic markers CD34 (0.13%). ELISA results showed that hDPSCs at passage 3 had the highest secretion levels of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF), with the highest secretion level of Neurotrophin-3 (NT-3) being at passage 2. Conclusion. hDPSCs have steady biological features of stem cells and exhibit optimal proliferation potential. hDPSCs at different passages have different capacities in the secretion of VEGF, BDNF, NGF, and NT-3. In conclusion cytokines secreted by hDPSCs may prove to be appropriate in the treatment of neurological diseases.

Abstract Background Shared decision-making (SDM) is preferred by many patients in cancer care. However, despite scientific evidence and promotion by health policy makers, SDM implementation in routine health care lags behind. This study aimed to evaluate an empirically and theoretically grounded implementation program for SDM in cancer care. Methods In a stepped wedge design, three departments of a comprehensive cancer center sequentially received the implementation program in a randomized order. It included six components: training for health care professionals (HCPs), individual coaching for physicians, patient activation intervention, patient information material/decision aids, revision of quality management documents, and reflection on multidisciplinary team meetings (MDTMs). Outcome evaluation comprised four measurement waves. The primary endpoint was patient-reported SDM uptake using the 9-item Shared Decision Making Questionnaire. Several secondary implementation outcomes were assessed. A mixed-methods process evaluation was conducted to evaluate reach and fidelity. Data were analyzed using mixed linear models, qualitative content analysis, and descriptive statistics. Results A total of 2,128 patient questionnaires, 559 questionnaires from 408 HCPs, 132 audio recordings of clinical encounters, and 842 case discussions from 66 MDTMs were evaluated. There was no statistically significant improvement in the primary endpoint SDM uptake. Patients in the intervention condition were more likely to experience shared or patient-lead decision-making than in the control condition (d=0.24). HCPs in the intervention condition reported more knowledge about SDM than in the control condition (d = 0.50). In MDTMs the quality of psycho-social information was lower in the intervention than in the control condition (d = − 0.48). Further secondary outcomes did not differ statistically significantly between conditions. All components were implemented in all departments, but reach was limited (e.g., training of 44% of eligible HCPs) and several adaptations occurred (e.g., reduced dose of coaching). Conclusions The process evaluation provides possible explanations for the lack of statistically significant effects in the primary and most of the secondary outcomes. Low reach and adaptations, particularly in dose, may explain the results. Other or more intensive approaches are needed for successful department-wide implementation of SDM in routine cancer care. Further research is needed to understand factors influencing implementation of SDM in cancer care. Trial registration clinicaltrials.gov, NCT03393351 , registered 8 January 2018.

Background and Aims. Teeth extracted are usually disposed as bio-waste whereas they could serve as an autologous tissue for culturing multipotent dental pulp cells which have application potential in regenerative medicine. This study aimed to examine the feasibility of cryopreserving dental pulp tissue at teeth extraction for later culturing of cells. Methods. The pulp tissue from each of a total of 10 teeth was cut into small fragments which were then divided into two portions. One portion was directly used for culturing pulp cells using the explant method. The other portion was cryopreserved with 10% DMSO in liquid nitrogen for at least one month and then thawed for culturing pulp cells. Results. Vital cells were obtained from all the 10 pulp fragment suspensions which went through cryopreservation. The cell outgrowth from the explants of cryopreserved pulp fragments was two days later than that of corresponding fresh pulp tissue. Otherwise, no difference was observed in proliferation, expression of stem cell markers and differentiation into adipose cells and osteoblasts between the two groups of cells cultured from the fresh or the cryopreserved pulp fragments. Conclusions. Cryopreserving fragmented dental pulp tissue provides a feasible option for saving pulp tissues as autologous cell sources for possible later application.

Biofilms are a major problem in hard-to-heal wounds. Moreover, they are composed of different species and are often tolerant to antimicrobial agents. At the same time, interspecific synergy and/or competition occurs when some bacterial species clash. For this reason, the tolerance of two dual-species wound biofilm models of Pseudomonas aeruginosa and Staphylococcus aureus or Enterococcus faecium against antimicrobials and antimicrobial dressings were analyzed quantitatively and by confocal laser scanning microscopy (CLSM). The results were compared to findings with planktonic bacteria. Octenidine-dihydrochloride/phenoxyethanol and polyhexamethylene biguanide (PHMB) irrigation solutions showed a significant, albeit delayed reduction in biofilm bacteria, while the PHMB dressing was not able to induce this effect. However, the cadexomer-iodine dressing caused a sustained reduction in and killed almost all bacteria down to 102 cfu/mL within 6 days compared to the control (1010 cfu/mL). By means of CLSM in untreated human biofilm models, it became evident that P. aeruginosa dominates over E. faecium and S. aureus. Additionally, P. aeruginosa appeared as a vast layer at the bottom of the samples, while S. aureus formed grape-like clusters. In the second model, the distribution was even clearer. Only a few E. faecium were visible, in contrast to the vast layer of P. aeruginosa. It seems that the different species avoid each other and seek their respective niches. These mixed-species biofilm models showed that efficacy and tolerance to antimicrobial substances are nearly species-independent. Their frequent application appears to be important. The bacterial wound biofilm remains a challenge in treatment and requires new, combined therapy options.

Abstract Backround This study was designed to analyse the value of preoperative Cone Beam CTs (CBCT) prior to the surgical removal of complex lower third molars. Furthermore, the aim was to assess injuries to the inferior alveolar nerve (IAN) bundle and postoperative neurological disorders depending on the position of the lower third molar and the inferior alveolar nerve bundle. Methods In this retrospective examination preoperative Cone Beam CTs and Orthopantomographs (OPT) of 324 patients were analysed concerning the location of the lower third molars in relation to the mandible and the inferior alveolar nerve bundle. Surgery protocols of all patients who underwent the surgical removal of at least one complex lower third molar were analysed concerning patient data, length of surgery, intraoperative haemorrhage, intraoperative exposure of the inferior alveolar nerve bundle, postoperative swelling and postoperative neurological disorders. The data was then compared to data from international studies. Results In all 324 patients a permanent neurological damage was not found. Temporary neurological damage was recorded in 13 cases (2.6%). A caudal nerve position with no measurable distance to the root of the lower third molar was associated with the highest risk of a temporal neurological damage. A vestibular touching nerve route also correlated with postoperative sensitivity impairment. If a mesioangulation (Winter) or a Pell and Gregory Type IIIC appears in the OPT, risk of neurological damage is at its highest. Conclusions Three-dimensional radiographic imaging, in our patient group, does not significantly affect the risk for complications during the surgical removal of complex lower third molars. Therefore, it should only be utilized for risk assessment, especially in cases of symptom-free lower third molars. A preoperative orthopantomogram still can be accepted as standard for radiographic imaging. An intraoperative exposure of the IAN bundle does not necessarily predict simultaneous neurological damage. Exposure of the IAN bundle is no indication for a discontinuation of the surgery.

BackgroundDCBLD1 is highly expressed in several kinds of cancer and plays a potential prognostic factor. However, the prognostic value and immune infiltration in head and neck squamous cell carcinoma remain unclear and need further research.Materials and MethodsDCBLD1 expression and clinical information were obtained from the Cancer Genome Atlas (TCGA) database. The mRNA level in cell lines (SCC25 and CAL27) and gingival fibroblasts were detected using quantitative PCR. Cox regression analysis was used to evaluate the prognostic values of DCBLD1 and clinical data in HNSCC. A nomogram was also established to predict the impact of DCBLD1 on prognosis based on Cox multivariate results. The methylation level of DCBLD1 in HNSC and its prognosis were analyzed in UALACN and MethSurv. Finally, the potential biological functions of DCBLD1 were investigated using gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA).ResultsThe mRNA and protein expression levels of DCBLD1 were highly expressed in HNSCC tissue and cell lines. The Cox analyses demonstrate that highly expressed DCBLD1 is an independent prognosis marker (p < 0.05). ROC curve analysis showed the performance of DCBLD1 (area under the ROC curve: 0.948, sensitivity: 93.2%, specificity: 84.7%). The methylation was increased in HNSCC patients compared with normal subjects (p < 0.05) and was associated with poor prognosis at sites cg27642470 and cg21104965. Additionally, DCBLD1 expression is poorly associated with immune cell infiltration and immunological checkpoints PD-L1 and TIM-3.ConclusionIn head and neck squamous cell carcinoma, DCBLD1 is overexpressed, associated with poor patient prognosis. The detailed underlying mechanism merits further research.

Silk fibroin is a biomaterial with multiple beneficial properties for use in regenerative medicine and tissue engineering. When dissolving and processing the reconstituted silk fibroin solution by electrospinning, the arrangement and size of fibers can be manifold varied and according fiber diameters reduced to the nanometer range. Such nonwovens show high porosity as well as potential biocompatibility. Usually, electrospinning of most biomaterials demands for the application of additives, which enable stable electrospinning by adjusting viscosity, and are intended to evaporate during processing or to be washed out afterwards. However, the use of such additives increases costs and has to be taken into account in terms of biological risks when used for biomedical applications.In this study, we explored the possibilities of additive-free electrospinning of pure fibroin nonwovens and tried to optimize process parameters to enable stable processing. We used natural silk derived from the mulberry silkworm Bombyx mori. After degumming, the silk fibroin was dissolved and the viscosity of the spinning solution was controlled by partial evaporation of the initial solving agent. This way, we were able to completely avoid the use of additives and manufacture nonwovens, which potentially offer higher biocompatibility and reduced immunogenicity. Temperature and relative humidity during electrospinning were systematically varied (25–35 °C, 25–30% RH). In a second step, the nonwovens optionally underwent methanol treatment to initiate beta-sheet formation in order to increase structural integrity and strength. Comprehensive surface analysis on the different nonwovens was performed using scanning electron microscopy and supplemented by additional mechanical testing. Cytotoxicity was evaluated using BrdU-assay, XTT-assay, LDH-assay and live-dead staining. Our findings were, that an increase of temperature and relative humidity led to unequal fiber diameters and defective nonwovens. Resistance to penetration decreased accordingly. The most uniform fiber diameters of 998 ± 63 nm were obtained at 30 °C and 25% relative humidity, also showing the highest value for resistance to penetration (0.20 N). The according pure fibroin nonwoven also showed no signs of cytotoxicity. However, while the biological response showed statistical evidence, the material characteristics showed no statistically significant correlation to changes of the ambient conditions within the investigated ranges. We suggest that further experiments should explore additional ranges for temperature and humidity and further focus on the repeatability of material properties in dependency of suitable process windows.

Introduction: Mesenchymal stromal/stem cells (MSCs) derived from fat tissue are an encouraging tool for regenerative medicine. They share properties similar to the bone marrow-derived MSCs, but the amount of MSCs per gram of fat tissue is 500x higher. The fat tissue can easily be digested by collagenase, releasing a heterogeneous cell fraction called stromal vascular fraction (SVF) which contains a variable amount of stromal/stem cells. In Europe, cell products like the SVF derived from fat tissue are considered advanced therapy medicinal product (ATMPs). As a consequence, the manufacturing process has to be approved via GMP-compliant process validation. The problem of the process validation for SVF is the heterogeneity of this fraction. Methods: Here, we modified existing purification strategies by adding an additional plastic adherence incubation of maximal 20 hours after SVF isolation. The resulting cell fraction was characterized and compared to SVF as well as cultivated adipose-derived stromal/stem cells (ASCs) with respect to viability and cell yield, the expression of surface markers, differentiation potential and cytokine expression. Results: Short-term incubation significantly reduced the heterogeneity of the resulting cell fraction compared to SVF. The cells were able to differentiate into adipocytes, chondrocytes, and osteoblasts. More importantly, they expressed trophic proteins which have been previously associated with the beneficial effects of MSCs. Furthermore, GMP compliance of the production process described herein was acknowledged by the national regulatory agencies (DE_BB_01_GMP_2017_1018). Conclusion: Addition of a short purification-step after the SVF isolation is a cheap and fast strategy to isolate a homogeneous uncultivated GMP-compliant cell fraction of ASCs.

The treatment of acute and chronic infected wounds with residing biofilm still poses a major challenge in medical care. Interactions of antimicrobial dressings with bacterial load, biofilm matrix and the overall protein-rich wound microenvironment remain insufficiently studied. This analysis aimed to extend the investigation on the efficacy of a variety of antimicrobial dressings using an in vitro biofilm model (lhBIOM) mimicking the specific biofilm-environment in human wounds. Four wound dressings containing polyhexanide (PHMB), octendine di-hydrochloride (OCT), cadexomer-iodine (C-IOD) or ionic silver (AG) were compared regarding their antimicrobial efficacy. Quantitative analysis was performed using a quantitative suspension method, separately assessing remaining microbial counts within the solid biofilm as well as the dressing eluate (representing the absorbed wound exudate). Dressing performance was tested against P. aeruginosa biofilms over the course of 6 days. Scanning electron microscopy (SEM) was used to obtain qualitative visualization on changes in biofilm structure. C-IOD demonstrated superior bacterial reduction. In comparison it was the only dressing achieving a significant reduction of more than 7 log10 steps within 3 days. Neither the OCT- nor the AG-containing dressing exerted a distinct and sustained antimicrobial effect. PHMB achieved a non-significant microbicidal effect (1.71 ± 0.31 log10 steps) at day 1. Over the remaining course (6 days) it demonstrated a significant microbistatic effect compared to OCT, AG and the control. Quantitative results in the dressing eluate correlate with those of the solid biofilm model. Overall, AG- and OCT-containing dressings did not achieve the expected anti-biofilm efficacy, while C-IOD performed best. Chemical interaction with the biofilms extrapolymeric substance (EPS), visualized in the SEM, and dressing configuration (agent concentration and release pattern) are suspected to be responsible. The unexpected low and diverse results of the tested antimicrobial dressings indicate a necessity to rethink non-debridement anti-biofilm therapy. Focussing on the combination of biofilm-disruptive (for EPS structure) and antimicrobial (for residing microorganisms) features, as with C-IOD, using dehydration and iodine, appears reasonably complementary and an optimal solution, as suggested by the here presented in vitro data.

SUMMARY. Precise perforator mapping of the epifascial and subcutaneous course of the perforator flaps, including the precise detection of the skin point, is mandatory for successful preoperative flap design and planning of supramicrosurgery. We investigated the effectiveness of contrast-enhanced B-flow (BCEUS) imaging for perforator mapping and preoperative perforator flap planning and compared it with B-flow ultrasound, contrast-enhanced ultrasound, and color Doppler ultrasound. Sixteen patients who received an individualized perforator flap reconstruction were included in the study. Preoperative perforator mapping includes the following structures: subfascial course of the pedicle, fascial penetration point, subcutaneous course (epifascial and subcutaneous), and perforator skin point. The precision of the preoperative perforator mapping was analyzed for color Doppler ultrasound, contrast-enhanced ultrasound, B-flow ultrasound, and BCEUS. Each technique was able to precisely display the subfascial course of the vascular pedicle, including the fascial penetration point. However, only BCEUS enabled precise mapping of the epifascial and subcutaneous (suprafascial) course, including the skin point of the perforators with a clear delineation. Precise knowledge of the suprafascial course of the perforators is mandatory for successful supermicrosurgery and perforator flap planning. BCEUS imaging facilitates full perforator mapping, which improves the safety of flap harvesting. However, BCEUS is technically demanding and requires an experienced sonographer.

Background/aimAtrial fibrillation (AF) is a major health problem and causes heart failure and stroke. Pathophysiological mechanisms indicate a link with oral health including periodontitis (PD), but supporting data are scarce. The aim was to investigate the link between features of oral health and the prevalence of AF.MethodsThis cross-sectional analysis of the Hamburg City Health Study included 5,634 participants with complete data on their PD and AF status. AF was assessed via self-reported questionnaire or medically diagnosed by standard 12-lead resting ECG. The oral health examination included full-mouth measurements of the dental plaque index (PI), the clinical attachment loss (CAL) at 6 sites per tooth, the bleeding on probing (BOP) and the decayed, missing and filled teeth (DMFT) index. Descriptive analyses for all variables stratified by the status of PD were performed. To test for an association between prevalent PD and prevalent AF, multivariable logistic regression models were used. Mediation analysis was used to test if interleukin-6 (IL-6) and/or C-reactive protein (CRP) mediated the association between PD and AF.ResultsAtrial fibrillation (prevalence: 5.6%) and the severity of PD (prevalence: moderate: 57.7%, severe: 18.9%) increased with age in men and women. Prevalent severe PD, CAL ≥3 mm, PI, and BOP were all associated with prevalent AF in unadjusted regression analysis. However, no association except for PI (odds ratio (OR): 1.22, 95% confidence interval (CI): 1.1-1.35, pConclusionThe study shows an association between prevalent AF and increased dental plaque levels indicated by a higher PI. In contrast, an association of prevalent PD with prevalent AF after adjustments for several confounders could not be demonstrated. Further studies are necessary to investigate the mechanisms underlying poor oral hygiene and AF as well as the influence of improved oral hygiene on AF onset.

Abstract Background Shared decision-making (SDM) has become increasingly important in health care. However, despite scientific evidence, effective implementation strategies, and a prominent position on the health policy agenda, SDM is not widely implemented in routine practice so far. Therefore, we developed a program for routine implementation of SDM in oncology by conducting an analysis of the current state and a needs assessment in a pilot study based on the Consolidated Framework for Implementation Research (CFIR). Based on these results, the main aim of our current study is to evaluate the process and outcome of this theoretically and empirically grounded multicomponent implementation program designed to foster SDM in routine cancer care. Methods We use a stepped wedge design, a variant of the cluster randomized controlled trial. The intervention to be implemented is SDM. Three participating clinics of one comprehensive cancer center will be randomized and receive the multicomponent SDM implementation program in a time-delayed sequence. The program consists of the following strategies: (a) SDM training for health care professionals, (b) individual coaching for physicians, (c) patient activation strategy, (d) provision of patient information material and decision aids, (e) revision of the clinics’ quality management documents, and (f) critical reflection of current organization of multidisciplinary team meetings. We will conduct a mixed methods outcome and process evaluation. The outcome evaluation will consist of four measurement points. The primary outcome is adoption of SDM, measured by the 9-item Shared Decision Making Questionnaire. A range of other implementation outcomes will be assessed (i.e., acceptability, readiness for implementing change, appropriateness, penetration). The implementation process will be evaluated using stakeholder interviews and field notes. This will allow adapting interventions if necessary. Discussion This study is the first large study on routine implementation of SDM conducted in German cancer care. We expect to foster implementation of SDM at the enrolled clinics. Insights gained from this study, using a theoretically and empirically grounded approach, can inform other SDM implementation studies and health policy developments, both nationally and internationally. Trial registration clinicaltrials.gov, NCT03393351. Registered 8 January 2018.

Objective: Despite numerous existing treatments for keloids, the responses in the clinic have been disappointing, due to either low efficacy or side effects. Numerous studies dealing with preclinical and clinical trials have been published about effective therapies for fibrotic diseases using mesenchymal stem cells; however, no research has yet been reported to scientifically investigate the effect of human dental pulp stem cells (HDPSCs) on the treatment of keloids. The objective is to provide an experimental basis for the application of stem cells in the treatment of keloids. Methods: Human normal fibroblasts (HNFs) and human keloid fibroblasts (HKFs) were cultured alone and in combination with HDPSCs using a transwell cell-contact-independent cell culture system. The effects of HDPSCs on HKFs were tested using a CCK-8 assay, live/dead staining assay, quantitative polymerase chain reaction, Western blot and immunofluorescence microscopy. Results: HDPSCs did not inhibit the proliferation nor the apoptosis of HKFs and HNFs. HDPSCs did, however, inhibit their migration. Furthermore, HDPSCs significantly decreased the expression of profibrotic genes (CTGF, TGF-β1 and TGF-β2) in HKFs and KNFs (p < 0.05), except for CTGF in HNFs. Moreover, HDPSCs suppressed the extracellular matrix (ECM) synthesis in HKFs, as indicated by the decreased expression of collagen I as well as the low levels of hydroxyproline in the cell culture supernatant (p < 0.05). Conclusions: The co-culture of HDPSCs inhibits the migration of HKFs and the expression of pro-fibrotic genes, while promoting the expression of anti-fibrotic genes. HDPSCs’ co-culture also inhibits the synthesis of the extracellular matrix by HKFs, whereas it does not affect the proliferation and apoptosis of HKFs. Therefore, it can be concluded that HDPSCs can themselves be used as a tool for restraining/hindering the initiation or progression of fibrotic tissue.

Aim: In order to provide adequate treatment to a patient with a subtype of Oromandibular Limb Hypogenesis Syndromes (OLHS), this study aimed to review and to analyze the current literature and treatment options of OLHS. Methods: Literature review in PubMed and Sciencedirect. Due to the small number of results, all available references were analyzed precisely. Results: Cases of OLHS are formerly rare and often incomplete. There are various classifications available, which, however, often seem confusing and are of little practical relevance. Furthermore, we present a complete case report of a patient with Charlie M syndrome, a type IV (Chicarilli)/ V (Hall) OLHS malformation. We also describe embryologic pathogenesis and differential diagnoses. Conclusion: As a result of our literature review, we recommend an adjusted classification for OLHS.

Periapical radiolucencies, which can be detected on panoramic radiographs, are one of the most common radiographic findings in dentistry and have a differential diagnosis including infections, granuloma, cysts and tumors. In this study, we seek to investigate the ability with which 24 oral and maxillofacial (OMF) surgeons assess the presence of periapical lucencies on panoramic radiographs, and we compare these findings to the performance of a predictive deep learning algorithm that we have developed using a curated data set of 2902 de-identified panoramic radiographs. The mean diagnostic positive predictive value (PPV) of OMF surgeons based on their assessment of panoramic radiographic images was 0.69 (±0.13), indicating that dentists on average falsely diagnose 31% of cases as radiolucencies. However, the mean diagnostic true positive rate (TPR) was 0.51 (±0.14), indicating that on average 49% of all radiolucencies were missed. We demonstrate that the deep learning algorithm achieves a better performance than 14 of 24 OMF surgeons within the cohort, exhibiting an average precision of 0.60 (±0.04), and an F1 score of 0.58 (±0.04) corresponding to a PPV of 0.67 (±0.05) and TPR of 0.51 (±0.05). The algorithm, trained on limited data and evaluated on clinically validated ground truth, has potential to assist OMF surgeons in detecting periapical lucencies on panoramic radiographs.

Despite increasing knowledge gained based on multidisciplinary research, plasma medicine still raises various questions regarding specific effects as well as potential risks. With regard to significant statements about in vivo applicability that cannot be prognosticated exclusively based on in vitro data, there is still a deficit of clinical data. This study included a clinical follow-up of five probands who had participated five years previously in a study on the influence of cold atmospheric pressure plasma (CAP) on the wound healing of CO2 laser-induced skin lesions. The follow-up included a complex imaging diagnostic involving dermatoscopy, confocal laser scanning microscopy (CLSM) and hyperspectral imaging (HSI). Hyperspectral analysis showed no relevant microcirculatory differences between plasma-treated and non-plasma-treated areas. In summary of all the findings, no malignant changes, inflammatory reactions or pathological changes in cell architecture could be detected in the plasma-treated areas. These unique in vivo long-term data contribute to a further increase in knowledge about important safety aspects in regenerative plasma medicine. However, to confirm these findings and secure indication-specific dose recommendations, further clinical studies are required.

Atherosclerotic lesions that critically narrow the artery can necessitate an angioplasty and stent implantation. Long-term therapeutic effects, however, are limited by excessive arterial remodeling. We here employed a miniaturized nitinol-stent coated with star-shaped polyethylenglycole (star-PEG), and evaluated its bio-functionalization with RGD and CXCL1 for improving in-stent stenosis after implantation into carotid arteries of mice. Nitinol foils or stents (bare metal) were coated with star-PEG, and bio-functionalized with RGD, or RGD/CXCL1. Cell adhesion to star-PEG-coated nitinol foils was unaltered or reduced, whereas bio-functionalization with RGD but foremost RGD/CXCL1 increased adhesion of early angiogenic outgrowth cells (EOCs) and endothelial cells but not smooth muscle cells when compared with bare metal foils. Stimulation of cells with RGD/CXCL1 furthermore increased the proliferation of EOCs. In vivo, bio-functionalization with RGD/CXCL1 significantly reduced neointima formation and thrombus formation, and increased re-endothelialization in apoE-/- carotid arteries compared with bare-metal nitinol stents, star-PEG-coated stents, and stents bio-functionalized with RGD only. Bio-functionalization of star-PEG-coated nitinol-stents with RGD/CXCL1 reduced in-stent neointima formation. By supporting the adhesion and proliferation of endothelial progenitor cells, RGD/CXCL1 coating of stents may help to accelerate endothelial repair after stent implantation, and thus may harbor the potential to limit the complication of in-stent restenosis in clinical approaches.