Alendronate reduces periosteal microperfusion in vivo.

Objectives: Bisphosphonates are known to induce a severe adverse effect known as medication-related osteonecrosis of the jaw (MRONJ). Previous studies have proven the impact of bisphosphonates on microperfusion; therefore, this study aimed to investigate alendronate-induced microcirculatory reactions in the calvarial periosteum of rats. Study design: Bone chambers were implanted into 48 Lewis rats. Microhemodynamics, inflammatory parameters, functional capillary density and defect healing were examined after alendronate treatment for two and six weeks using repetitive intravital fluorescence microscopy for two weeks. Results: Microhemodynamics remained unchanged. In alendronate-treated rats, inflammation was slightly increased, functional capillary density was significantly reduced (day 10: controls 100.45 ± 5.38 cm/cm2, two weeks alendronate treatment 44.77 ± 3.55 cm/cm2, six weeks alendronate treatment 27.54 ± 2.23 cm/cm2) and defect healing was decelerated. The changes in functional capillary density and defect healing were dose-dependent. Conclusion: The bisphosphonate alendronate has a significant negative impact on periosteal microperfusion in vivo. This could be a promising target for the treatment of MRONJ.

Impact of acceleration on bone depiction quality by ultrashort echo time magnetic resonance bone imaging sequences in medication-related osteonecrosis of the jaw.

Objectives: To assess the impact on bone depiction quality by decreasing number of radial acquisitions (RA) of a UTE MR bone imaging sequence in MRONJ. Material and methods: UTE MR bone imaging sequences using pointwise encoding time reduction with RA (PETRA) with 60'000, 30'000 and 10'000 RA were acquired in 16 patients with MRONJ and 16 healthy volunteers. Blinded readout sessions were performed by two radiologists. Qualitative analysis compared the detection of osteolytic lesions and productive bony changes in the PETRA sequences of the patients with MRONJ. Quantitative analysis assessed the differences in image artifacts, contrast-to-noise ratio (CNR) and image noise. Results: Acquisition times were reduced from 315 to 165 and 65 s (60'000, 30'000, 10'000 RA, respectively), resulting in a fewer number of severe motion artifacts. Bone delineation was increasingly blurred when reducing the number of RA but without any trade-off in terms of diagnostic performance. Interreader agreement for the detection of pathognomonic osteolysis was moderate (κ = 0.538) for 60'000 RA and decreased to fair (κ = 0.227 and κ = 0.390) when comparing 30'000 and 10'000 RA, respectively. Image quality between sequences was comparable regarding CNR, image noise and artifact dimensions without significant differences (all P > 0.05). Conclusions: UTE MR bone imaging sequences with a lower number of RA provide sufficient image quality for detecting osteolytic lesions and productive bony changes in MRONJ subjects at faster acquisition times compared to the respective standard UTE MR bone imaging sequence.

Correlation of dynamic contrast-enhanced bone perfusion with morphologic ultra-short echo time MR imaging in medication-related osteonecrosis of the jaw.

OBJECTIVES: To investigate whether dynamic contrast-enhanced (DCE)-MR bone perfusion could serve as surrogate for morphologic ultra-short echo time (UTE) bone images and to correlate perfusion with morphologic hallmarks in histologically proven foci of medication-related osteonecrosis of the jaw (MRONJ). METHODS: Retrospective study including 20 patients with established diagnosis of MRONJ. Qualitative consensus assessment of predefined jaw regions by two radiologists was used as reference standard using Likert scale (0-3) for standard imaging hallmarks in MRONJ (osteolysis, sclerosis, periosteal thickening). DCE-MRI measurements performed in corresponding regions of the mandible were then correlated with qualitative scores. Regions were grouped into "non-affected" and "pathologic" based on binarized Likert scores of different imaging hallmarks (0-1 vs 2-3). DCE-MRI measurements among hallmarks were compared using Mann-Whitney-U-testing. ROC (receiver-operating-characteristic) analysis was performed for each of the perfusion parameters to assess diagnostic performance for identification of MRONJ using morphologic ratings as reference standard. RESULTS: Median perfusion measurements of "pathologic" regions in wash-in, peak enhancement intensity and integrated area under the curve are significantly higher than those of "non-affected" regions, irrespective of reference imaging hallmark (p < 0.05). No significant perfusion differences were found between "pathologic" regions with and without osteolysis (p = 0.180). ROC analysis showed fair diagnostic performance of DCE-MRI parameters for identification of MRONJ (AUC 0.626-0.727). CONCLUSIONS: DCE bone perfusion parameters are significantly increased in MRONJ compared to non-affected regions, irrespective of osteolysis. Due to certain overlap DCE-MRI bone perfusion cannot serve as full surrogate for UTE bone imaging but may enhance reader confidence.

Propionate attenuates atherosclerosis by immune-dependent regulation of intestinal cholesterol metabolism.

AIMS: Atherosclerotic cardiovascular disease (ACVD) is a major cause of mortality and morbidity worldwide, and increased low-density lipoproteins (LDLs) play a critical role in development and progression of atherosclerosis. Here, we examined for the first time gut immunomodulatory effects of the microbiota-derived metabolite propionic acid (PA) on intestinal cholesterol metabolism. METHODS AND RESULTS: Using both human and animal model studies, we demonstrate that treatment with PA reduces blood total and LDL cholesterol levels. In apolipoprotein E-/- (Apoe-/-) mice fed a high-fat diet (HFD), PA reduced intestinal cholesterol absorption and aortic atherosclerotic lesion area. Further, PA increased regulatory T-cell numbers and interleukin (IL)-10 levels in the intestinal microenvironment, which in turn suppressed the expression of Niemann-Pick C1-like 1 (Npc1l1), a major intestinal cholesterol transporter. Blockade of IL-10 receptor signalling attenuated the PA-related reduction in total and LDL cholesterol and augmented atherosclerotic lesion severity in the HFD-fed Apoe-/- mice. To translate these preclinical findings to humans, we conducted a randomized, double-blinded, placebo-controlled human study (clinical trial no. NCT03590496). Oral supplementation with 500 mg of PA twice daily over the course of 8 weeks significantly reduced LDL [-15.9 mg/dL (-8.1%) vs. -1.6 mg/dL (-0.5%), P = 0.016], total [-19.6 mg/dL (-7.3%) vs. -5.3 mg/dL (-1.7%), P = 0.014] and non-high-density lipoprotein cholesterol levels [PA vs. placebo: -18.9 mg/dL (-9.1%) vs. -0.6 mg/dL (-0.5%), P = 0.002] in subjects with elevated baseline LDL cholesterol levels. CONCLUSION: Our findings reveal a novel immune-mediated pathway linking the gut microbiota-derived metabolite PA with intestinal Npc1l1 expression and cholesterol homeostasis. The results highlight the gut immune system as a potential therapeutic target to control dyslipidaemia that may introduce a new avenue for prevention of ACVDs.

ASA score and procedure type predict complications and costs in maxillofacial reconstructive surgery: a retrospective study using a hospital administrative database.

BACKGROUND: Reconstruction of osseous and soft tissue defects after surgical resection of oral cavity cancers can be achieved by a single-stage procedure with a microvascular bone flap or by a two-step approach with a soft tissue flap and subsequent bone augmentation. The therapeutic approach should be selected based on the patient’s needs. Economic pressure requires preoperative risk assessment and estimation of the postoperative course. Flat-rate reimbursement systems via diagnosis-related groups with insufficient morbidity adjustments and financial sanction of medical complications might additionally cause false incentives in the choice of treatment. OBJECTIVE: This study aimed to assess the influence of the type of flap chosen for maxillofacial reconstructive surgery on the total costs. Complication rates of different types of flap surgery and their prediction by a preoperative risk assessment tool (American Society of Anesthesiologists [ASA] score) were determined. Overall, the fairness of the current reimbursement system was rated. METHODS: Patient characteristics, clinical data, and data on total costs and reimbursement of patients aged 18 years and older having undergone maxillofacial reconstructive flap surgery at the University Hospital of Zurich (Switzerland) between 2012 and 2014 were analysed. The preoperative risk was classified by the ASA score. Complications were graded according to the Clavien-Dindo classification system and the comprehensive complication index (CCI). Statistical analysis included Spearman and Pearson rank correlation, Kruskal-Wallis and Mann-Whitney nonparametric tests, and linear regression analysis. RESULTS: 129 patients were included in this study. Soft tissue flaps were performed in 82 patients, of which 56 were radial forearm flaps (43.4%), bone flaps in 41 patients, of which 32 were fibula flaps (24.8%), and combined flaps in 6 patients (4.7%). Patients with fibula flaps showed a significantly higher CCI and higher total costs. Higher preoperative ASA scores were significantly associated with increased length of stay, total costs and complications. Both the ASA score and reconstruction with a radial forearm flap were significant predictors of complications and total costs. Total median costs for radial forearm flaps were CHF 50,560 (reimbursement: CHF 60,851; difference: CHF 10,291) and for fibula flaps CHF 66,982 (reimbursement: CHF 58,218; difference: CHF −8,764). CONCLUSION: The ASA score allows a reliable preoperative assessment of patient outcomes and financial burden in maxillofacial reconstructive flap surgery. The type of flap reconstruction significantly influences complications and ultimately total costs. The current reimbursement system via diagnosis-related groups (DRGs) does not take sufficient account of this fact. Adaptations are therefore needed to prevent misplaced incentives to the detriment of patients.

[Cinematic Rendering in Cone Beam Computed Tomography: Advanced 3D Reconstructions of Dental and Maxillofacial Pathologies]. / Cinematic Rendering in der Digitalen Volumentomografie.

Cinematic rendering (CR) is a novel 3D visualisation technique, which provides photorealistic image reconstructions with a high level of image details. Aim of this case series is to show the application of CR in Cone Beam Computed Tomography (CBCT) in dentomaxillofacial pathologies. Four exemplary CBCTs of clinical dentomaxillofacial cases were selected. 3D CR reconstructions were generated from the CBCT by using a vendor-provided standard CR software. Cases include 1) external tooth resorption, 2) ankylosed maxillary molar tooth, 3) giant cell-associated osteolytic lesion of the mandible, 4) unilateral cleft lip/palate with additional skeletofacial deformity. CBCTs of four patients showing dental and osseous pathologies were successfully reconstructed. Overall, a subjectively improved 3D understanding of the presented pathologies was observed. The CR images seem to present more plasticity, giving a better feeling for the spatial depth of the tissue. CR can be applied to CBCT images in dentomaxillofacial patients. The photorealistic appearance might improve the understanding of complex anatomy or pathology, could facilitate patient communication, and might be helpful for advanced medical education. We see potential in the use of CR for additional 3D visualization. The actual image diagnosis is done in the classic sectional planes. The significance of CR reconstruction for image diagnostics must be investigated in appropriate studies.

Cell seeding accelerates the vascularization of tissue engineering constructs in hypertensive mice.

Rapid blood vessel ingrowth into transplanted constructs represents the key requirement for successful tissue engineering. Seeding three-dimensional scaffolds with suitable cells is an approved technique for this challenge. Since a plethora of patients suffer from widespread diseases that limit the capacity of neoangiogenesis (e.g., hypertension), we investigated the incorporation of cell-seeded poly-L-lactide-co-glycolide scaffolds in hypertensive (BPH/2J, group A) and nonhypertensive (BPN/3J, group B) mice. Collagen-coated scaffolds (A1 and B1) were additionally seeded with osteoblast-like (A2 and B2) and mesenchymal stem cells (A3 and B3). After implantation into dorsal skinfold chambers, inflammation and newly formed microvessels were measured using repetitive intravital fluorescence microscopy for 2 weeks. Apart from a weak inflammatory response in all groups, significantly increased microvascular densities were found in cell-seeded scaffolds (day 14, A2: 192 ± 12 cm/cm2, A3: 194 ± 10 cm/cm2, B2: 249 ± 19 cm/cm2, B3: 264 ± 17 cm/cm2) when compared with controls (A1: 129 ± 10 cm/cm2, B1: 185 ± 8 cm/cm2). In this context, hypertensive mice showed reduced neoangiogenesis in comparison with nonhypertensive animals. Therefore, seeding approved scaffolds with organ-specific or pluripotent cells is a very promising technique for tissue engineering in hypertensive organisms.

Antimicrobial peptide gene expression in medication-related osteonecrosis of the jaw.

Bisphosphonates and denosumab are commonly used antiresorptive therapies in patients with bone metastasis and osteoporosis. Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect of these drugs, and infection has been recognized as a contributing factor. Current therapeutic options for MRONJ show limited effectiveness, therefore necessitating novel treatment strategies. Bisphosphonates have recently been reported to induce the expression of antimicrobial peptides (AMPs), an inherent component of the immune system. Therefore, the aim of the present study was to investigate and compare the influence of the anti-RANKL antibody denosumab and bisphosphonates on the gene expression of selected AMPs: human α-defensin-1, human α-defensin-3, human ß-defensin-1, and human ß-defensin-3. Bone specimens were collected from patients with MRONJ who had been treated with bisphosphonates (n = 6) or denosumab (n = 6), and from healthy subjects (n = 6) with no history of treatment with bone metabolism-influencing drugs. Reverse transcription-quantitative polymerase chain reaction was used to quantify the expression levels of selected AMPs. Samples from patients treated with denosumab showed significantly higher mRNA expression of human α-defensin-3 and human ß-defensin-3 than those from healthy subjects. This finding is similar to previously described upregulated expression of human defensins in patients with MRONJ after bisphosphonates treatment. This suggests that the elevated expression of defensins may be at least a part of the mechanism underlying the pathogenesis of osteonecrosis induced by antiresorptive therapies, which can serve as a new target for potential treatment of MRONJ.

Age-related differences in actual-ideal personality trait level discrepancies.

People differ from each other in their typical patterns of behavior, thought, and emotion and these patterns are considered to constitute their personalities (Funder, 2001). For various reasons, for example, because certain trait levels may help to attain certain goals or fulfill certain social roles, people may experience that their actual trait levels are different from their ideal trait levels. In this study, we investigated (a) the impact of age on discrepancies between actual and ideal Big Five personality trait levels and (b) the impact of these discrepancies on personality trait changes across a period of 2 years. We use data of a large, nationally representative, and age-diverse sample (N = 4,057, 17-94 years, M = 53 years). Results largely confirmed previously reported age effects on actual personality trait levels but were sometimes more complex. Ideal trait levels exceeded actual trait levels more strongly for younger compared with older adults. Unexpectedly, neither ideal trait levels nor their interaction with beliefs about the extent to which personality is malleable versus fixed predicted trait change over 2 years (controlling for actual trait levels). We conclude that ideal-actual trait level discrepancies may provide an impetus for change but that they appear to neither alone nor in combination with the belief that personality trait change is possible suffice to produce such change. We discuss commitment, self-efficacy, and strategy knowledge as potential additional predictors of trait change. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Histometabolic Tumor Imaging of Hypoxia in Oral Cancer: Clinicopathological Correlation for Prediction of an Aggressive Phenotype.

INTRODUCTION: Fluorodeoxyglucose-positron emission tomography (FDG-PET) is a widely used imaging tool for oral squamous cell carcinoma (OSCC). Preliminary studies indicate that quantification of tumor metabolic uptake may correlate with tumor hypoxia and aggressive phenotypes. METHODS: Retrospective review of a consecutive cohort of OSCC (n = 98) with available pretherapeutic FDG-PET/CT, treated at the University Hospital Zurich. Clinico-pathologico-radiological correlation between maximum standard uptake value (SUVmax) of the primary tumor, immunohistochemical staining for hypoxia-related proteins glucose transporter 1 (GLUT1) and hypoxia-inducible factor 1-alpha (HIF1a), depth of invasion (DOI), lymph node metastasis, and outcome was examined. RESULTS: Positive staining for GLUT1 and HIF1a on immunohistopathological analysis correlated with increased SUVmax on pretherapeutic imaging and with increased DOI (Kruskal-Wallis, P = 0.037, and P = 0.008, respectively). SUVmax and DOI showed a strong positive correlation (Spearman Rho, correlation coefficient = 0.451, P = 0.0003). An increase in SUVmax predicted nodal metastasis (Kruskal-Wallis, P = 0.017) and poor local control (log rank, P = 0.047). CONCLUSION: In OSCC, FDG-PET-derived metabolic tumor parameter SUVmax serves as a surrogate marker for hypoxia and can be used to predict tumor aggressiveness, with more invasive phenotypes and poorer local control.

Correction: Stalder, et al.; Value of SUVmax for the Prediction of Bone Invasion in Oral Squamous Cell Carcinoma. Biology 2020, 9, 23.

The authors would like to make a correction to their published paper [1][...].

Changing How Race Is Portrayed in Medical Education: Recommendations From Medical Students.

The medical community has been complicit in legitimizing claims of racial difference throughout the history of the United States. Unfortunately, a rigorous examination of the role medicine plays in perpetuating inequity across racial lines is often missing in medical school curricula due to time constraints and other challenges inherent to medical education. The imprecise use of race-a social construct-as a proxy for pathology in medical education is a vestige of institutionalized racism. Recent examples are presented that illustrate how attributing outcomes to race may contribute to bias and unequal care. This paper proposes the following recommendations for guiding efforts to mitigate the adverse effects associated with the use of race in medical education: emphasize the need for incoming students to be familiar with how race can influence health outcomes; provide opportunities to hold open conversations about race in medicine among medical school faculty, students, and staff; craft and implement protocols that address and correct the inappropriate use of race in medical school classes and course materials; and encourage a large cultural shift within the field of medicine. Adoption of an interdisciplinary approach that taps into many fields, including ethics, history, sociology, evolutionary genetics, and public health is a necessary step for cultivating more thoughtful physicians who will be better prepared to care for patients of all racial and ethnic backgrounds.

Impact of the Gut Microbiota on Atorvastatin Mediated Effects on Blood Lipids.

BACKGROUND AND AIMS: The mechanisms of interindividual variation of lipid regulation by statins, such as the low-density lipoprotein cholesterol (LDL) lowering effects, are not fully understood yet. Here, we used a gut microbiota depleted mouse model to investigate the relation between the gut microbiota and the regulatory property of atorvastatin on blood lipids. METHODS: Mice (C57BL/6) with intact gut microbiota or antibiotic induced abiotic mice (ABS) were put on standard chow diet (SCD) or high fat diet (HFD) for six weeks. Atorvastatin (10 mg/kg body weight/day) or a control vehicle were applied per gavage for the last four weeks of dietary treatment. Blood lipids including total cholesterol, very low-density lipoprotein, low-density lipoprotein, high-density lipoprotein and sphingolipids were measured to probe microbiota-dependent effects of atorvastatin. The expression of genes involved in hepatic and intestinal cholesterol metabolism was analyzed with qRT-PCR. The alteration of the microbiota profile was examined using 16S rRNA qPCR in mice with intact gut microbiota. RESULTS: HFD feeding significantly increased total blood cholesterol and LDL levels, as compared to SCD in both mice with intact and depleted gut microbiota. The cholesterol lowering effect of atorvastatin was significantly attenuated in mice with depleted gut microbiota. Moreover, we observed a global shift in the abundance of several sphingolipids upon atorvastatin treatment which was absent in gut microbiota depleted mice. The regulatory effect of atorvastatin on the expression of distinct hepatic and intestinal cholesterol-regulating genes, including Ldlr, Srebp2 and Npc1l1 was altered upon depletion of gut microbiota. In response to HFD feeding, the relative abundance of the bacterial phyla Bacteroidetes decreased, while the abundance of Firmicutes increased. The altered ratio between Firmicutes to Bacteroidetes was partly reversed in HFD fed mice treated with atorvastatin. CONCLUSIONS: Our findings support a regulatory impact of atorvastatin on the gut microbial profile and, in turn, demonstrate a crucial role of the gut microbiome for atorvastatin-related effects on blood lipids. These results provide novel insights into potential microbiota-dependent mechanisms of lipid regulation by statins, which may account for variable response to statin treatment.

Value of SUVmax for the Prediction of Bone Invasion in Oral Squamous Cell Carcinoma.

In advanced oral squamous cell carcinoma (OSCC), accurate planning of surgical resection and reconstruction are crucial for outcome and postoperative function. For OSCC close to the maxilla or mandible, prediction of bone invasion is necessary. The aim of this study was to examine whether metabolic tumor imaging obtained by fluorodeoxyglucose positron emission tomography (FDG-PET) could enhance preoperative predictability of bone invasion. We performed an analysis of 84 treatment-naïve OSCCs arising from gum (upper and lower), hard palate, floor of mouth, and retromolar trigone treated at the University Hospital Zurich, Switzerland, who underwent wide local excision with free flap reconstruction between 04/2010 and 09/2018 and with available preoperative FDG-PET. Prediction of bone invasion by metabolic tumor imaging such as maximum standardized uptake value (SUVmax) was examined. On definitive histopathology, bone invasion was present in 47 of 84 cases (56%). The probability of bone infiltration increased with a higher pretherapeutic SUVmax in an almost linear manner. A pretherapeutic SUVmax of primary tumor below 9.5 ruled out bone invasion preoperatively with a high specificity (97.6%). The risk of bone invasion was 53.6% and 71.4% for patients with SUVmax between 9.5-14.5 and above 14.5, respectively. Patients with bone invasion had worse distant metastasis-free survival compared to patients without bone invasion (log-rank test, p = 0.032). In conclusion, metabolic tumor imaging using FDG-PET could be used to rule out bone invasion in oral cancer patients and may serve in treatment planning.

Turnover, Burnout, and Job Satisfaction of Certified Registered Nurse Anesthetists in the United States: Role of Job Characteristics and Personality.

This study, designed to identify the determinants of job satisfaction, employee burnout, and turnover intentions, was based on data derived from a survey of members of the American Association of Nurse Anesthetists (AANA) who were active Certified Registered Nurse Anesthetists (CRNAs). The relationships explored, using structural equation models, were job satisfaction as a function of job characteristics and personality factors; employee burnout as a function of job characteristics, personality factors, and demographic characteristics; and turnover as a function of job satisfaction and burnout. Job satisfaction was positively associated with the job characteristic autonomy and the personality factor agreeableness. Employee burnout was negatively associated with the job characteristics autonomy and skill variety, and with the personality factors agreeableness, stability, and openness; it was positively associated with hours worked per week. Turnover intentions were negatively associated with job satisfaction and positively associated with burnout. The results suggest that employers should structure CRNA jobs to feature greater skill variety and greater autonomy, which should result in higher job satisfaction, less burnout, and lower turnover intentions.

Medication-Related Osteonecrosis of the Jaw-Comparison of Bone Imaging Using Ultrashort Echo-Time Magnetic Resonance Imaging and Cone-Beam Computed Tomography.

OBJECTIVE: The aim of this study was to compare bone imaging between ultrashort echo-time (UTE) magnetic resonance (MR) imaging and cone-beam computed tomography (CBCT) as the reference standard in patients with medication-related osteonecrosis of the jaw (MRONJ). MATERIALS AND METHODS: A 1-year retrospective, blinded, and randomized qualitative analysis of UTE MR images and CBCT from 19 patients with clinically diagnosed MRONJ was performed by 2 independent radiologists. Medication-related osteonecrosis of the jaw imaging hallmarks such as osteolysis, periosteal thickening, and medullary osteosclerosis were rated visually (0 and 1 to 3 for normal and mild to severe changes) for defined anatomic regions of the jaw. In addition, segmentation of these regions was performed on coregistered MR/CBCT images for the following quantitative comparison of signal intensity (SI) on MR and gray values (GVs) on CBCT images. Interreader/modality agreement (Cohen kappa), standard testing for significant differences of (non)parametric values, and Pearson correlation of signal intensity/GV were used for statistical analysis. RESULTS: The anterior corpus of the mandible was most often affected by MRONJ (P < 0.001). Overall, interreader agreement of qualitative MRONJ hallmark scores was almost perfect (κ = 0.81) and without significant differences between modalities (κ = 0.81 vs 0.82, CBCT vs MR, respectively). Intermodality agreement for qualitative gradings was substantial for both readers (κ = 0.77 and 0.70). Signal intensity/GV in MRONJ-affected areas differed significantly from healthy bone (P < 0.001) as well as correlation significantly between modalities (r = -0.77; P < 0.001). CONCLUSIONS: Qualitative assessment of MRONJ with radiation-free UTE MR imaging is comparable to reference standard CBCT. Quantitative measurements of both modalities significantly distinguish diseased from normal bone with strong correlations among the quantitative values in both modalities.

[CAD/CAM Revolution in Craniofacial Reconstruction]. / Die CAD/CAM-Revolution in der kraniofazialen Rekonstruktion.

CAD/CAM Revolution in Craniofacial Reconstruction Abstract. The face is an important part of the personality and at the same time fulfils a variety of tasks. Aesthetics and function form a unique unit. The formation of the field of oral and maxillofacial surgery began in the first decades of the last century. It includes the prevention, diagnosis, therapy and rehabilitation of diseases, injuries, malformations and changes of the complex structures of the face, oral cavity, jaw and teeth. In the meantime, oral and maxillofacial surgery has arrived in the 21st century. Today's oral and maxillofacial surgery is a link between medicine and dentistry and a protagonist in the implementation of digital workflows in clinical care. Individual solutions with patient-specific implants are the rule, computer-assisted techniques support the surgeon in the planning and performing of surgical procedures. This article intends to give you an insight into how our patients benefit from advanced technologies.

Long noncoding RNA NEAT1 modulates immune cell functions and is suppressed in early onset myocardial infarction patients.

AIMS: Inflammation is a key driver of atherosclerosis and myocardial infarction (MI), and beyond proteins and microRNAs (miRs), long noncoding RNAs (lncRNAs) have been implicated in inflammation control. To obtain further information on the possible role of lncRNAs in the context of atherosclerosis, we obtained comprehensive transcriptome maps of circulating immune cells (peripheral blood mononuclear cells, PBMCs) of early onset MI patients. One lncRNA significantly suppressed in post-MI patients was further investigated in a murine knockout model. METHODS AND RESULTS: Individual RNA-sequencing (RNA-seq) was conducted on PBMCs from 28 post-MI patients with a history of MI at age ≤50 years and stable disease ≥3 months before study participation, and from 31 healthy individuals without manifest cardiovascular disease or family history of MI as controls. RNA-seq revealed deregulated protein-coding transcripts and lncRNAs in post-MI PBMCs, among which nuclear enriched abundant transcript (NEAT1) was the most highly expressed lncRNA, and the only one significantly suppressed in patients. Multivariate statistical analysis of validation cohorts of 106 post-MI patients and 85 controls indicated that the PBMC NEAT1 levels were influenced (P = 0.001) by post-MI status independent of statin intake, left ventricular ejection fraction, low-density lipoprotein or high-density lipoprotein cholesterol, or age. We investigated NEAT1-/- mice as a model of NEAT1 deficiency to evaluate if NEAT1 depletion may directly and causally alter immune regulation. RNA-seq of NEAT1-/- splenocytes identified disturbed expression and regulation of chemokines/receptors, innate immunity genes, tumour necrosis factor (TNF) and caspases, and increased production of reactive oxygen species (ROS) under baseline conditions. NEAT1-/- spleen displayed anomalous Treg and TH cell differentiation. NEAT1-/- bone marrow-derived macrophages (BMDMs) displayed altered transcriptomes with disturbed chemokine/chemokine receptor expression, increased baseline phagocytosis (P < 0.0001), and attenuated proliferation (P = 0.0013). NEAT1-/- BMDMs responded to LPS with increased (P < 0.0001) ROS production and disturbed phagocytic activity (P = 0.0318). Monocyte-macrophage differentiation was deregulated in NEAT1-/- bone marrow and blood. NEAT1-/- mice displayed aortic wall CD68+ cell infiltration, and there was evidence of myocardial inflammation which could lead to severe and potentially life-threatening structural damage in some of these animals. CONCLUSION: The study indicates distinctive alterations of lncRNA expression in post-MI patient PBMCs. Regarding the monocyte-enriched NEAT1 suppressed in post-MI patients, the data from NEAT1-/- mice identify NEAT1 as a novel lncRNA-type immunoregulator affecting monocyte-macrophage functions and T cell differentiation. NEAT1 is part of a molecular circuit also involving several chemokines and interleukins persistently deregulated post-MI. Individual profiling of this circuit may contribute to identify high-risk patients likely to benefit from immunomodulatory therapies. It also appears reasonable to look for new therapeutic targets within this circuit.