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.

Modified technique for rehabilitation of facial paralysis using autogenous fascia lata grafts.

PURPOSE: In this retrospective study we used a modified surgical technique for midface reanimation in patients with facial nerve paralysis. Facial atonicity can cause functional impairment regarding speech articulation, oral competence, breathing, and eyelid closure. Furthermore, esthetic and psychological aspects play an important role in patients' emotional interaction and social integration. The chosen rehabilitative technique should offer support against prolapse of facial structures and remedy of functional disabilities and, thereby, prevention of social stigmatization due to disease-related changes in appearance. MATERIALS AND METHODS: Between 2005 and 2013, fascia lata grafts were used as static support in 15 cases of unilateral facial paralysis. Two fascia lata grafts were subcutaneously inserted in the upper and lower lips crossing the midline and sutured at 4 points, including the unaffected part of the orbicularis oris muscle and modiolus. The slings were suspended against the zygomatic arch with an osteosynthesis plate. RESULTS: The patients perceived surgery results as considerably improving their appearance, speech, and alimentation. In 93.3% of cases, no postoperative complications occurred. The follow-up results (8 months to 8 years) remained stable. CONCLUSIONS: This retrospective study showed the advantages of static facial reanimation in appropriate cases. The bony fixated support of the fascial slings allows an immediate improvement of facial symmetry. Additional attachment points including the unaffected part of the orbicularis oris muscle and the use of 2 independent fascia lata slings allow a more accurate adjustment of suspension forces and an incomplete dynamic reanimation of the mouth corner. With respect to its simplicity and minimal invasiveness, this surgical procedure is associated with low morbidity and rapid improvement of the patient's esthetic appearance.

Effects of a new piezoelectric device on periosteal microcirculation after subperiosteal preparation.

INTRODUCTION: Subperiosteal preparation using a periosteal elevator leads to disturbances of local periosteal microcirculation. Soft-tissue damage can usually be considerably reduced using piezoelectric technology. For this reason, we investigated the effects of a novel piezoelectric device on local periosteal microcirculation and compared this approach with the conventional preparation of the periosteum using a periosteal elevator. MATERIAL AND METHODS: A total of 20 Lewis rats were randomly assigned to one of two groups. Subperiosteal preparation was performed using either a piezoelectric device or a periosteal elevator. Intravital microscopy was performed immediately after the procedure as well as three and eight days postoperatively. Statistical analysis of microcirculatory parameters was performed offline using analysis of variance (ANOVA) on ranks (p<0.05). RESULTS: At all time points investigated, intravital microscopy demonstrated significantly higher levels of periosteal perfusion in the group of rats that underwent piezosurgery than in the group of rats that underwent treatment with a periosteal elevator. CONCLUSION: The use of a piezoelectric device for subperiosteal preparation is associated with better periosteal microcirculation than the use of a conventional periosteal elevator. As a result, piezoelectric devices can be expected to have a positive effect on bone metabolism.

Non-radiological method for three-dimensional implant position evaluation using an intraoral scan method.

INTRODUCTION: This technical innovation presents a method that reproduces the position of a dental implant after insertion without the reuse of X-ray radiation. MATERIAL AND METHODS: An implant was inserted into the natural gap between the canines and premolars of three domestic pigs. A Straumann Scanbody was then screwed to the implant, and a digital impression of the jaw segment was made. The scanbody was scanned using a hand-held scanner. This was followed by the radiological detection of implant position on a CBCT. On the computer, the position of the implant was calculated and compared with the radiologically detected position. RESULTS: The calculated and determined position of the dental implant by the scanner is in good agreement with the radiologically controlled position. DISCUSSION: Evaluating the position of implants using intraoral scans is an easy and radiation-free method of three-dimensional site assessment after superimposition over a three-dimensional data set.

Diagnosis and treatment of optic nerve trauma.

Decreasing visual acuity secondary to orbital trauma or orbital and anterior skull base surgery may be caused by either sudden space-occupying intraorbital lesions, including retrobulbar hemorrhage (RBH), or direct damage to the prechiasmatic pathway. Contrary to traumatic optic neuropathy, RBH must be diagnosed and treated immediately to prevent permanent damage to the visual system. Therefore, monitoring and handling of visual pathway damage are mandatory. Flash visual evoked potentials and electroretinograms can provide evidence of the status of conductivity of the visual pathway when clinical assessment is not feasible. Both are thus essential diagnostic procedures not only for primary diagnosis but also for intraoperative evaluation. In case of RBH surgical decompression is compulsory. However, traumatic optic neuropathy does not respond to either corticosteroids or optic canal surgery. Modern craniomaxillofacial surgery requires detailed consideration of the diagnosis and treatment of traumatic visual pathway damage with the ultimate goal of preserving visual acuity.

Modulation of the Serum Metabolome by the Short-Chain Fatty Acid Propionate: Potential Implications for Its Cholesterol-Lowering Effect.

(1) Background: Dyslipidemia represents a major risk factor for atherosclerosis-driven cardiovascular disease. Emerging evidence suggests a close relationship between cholesterol metabolism and gut microbiota. Recently, we demonstrated that the short-chain fatty acid (SCFA) propionate (PA) reduces serum cholesterol levels through an immunomodulatory mechanism. Here, we investigated the effects of oral PA supplementation on the human serum metabolome and analyzed changes in the serum metabolome in relation to the cholesterol-lowering properties of PA. (2) Methods: The serum metabolome of patients supplemented with either placebo or propionate orally for 8 weeks was assessed using a combination of flow injection analysis-tandem (FIA-MS/MS) as well as liquid chromatography (LC-MS/MS) and mass spectrometry using a targeted metabolomics kit (MxP®Quant 500 kit: BIOCRATES Life Sciences AG, Innsbruck, Austria). A total of 431 metabolites were employed for further investigation in this study. (3) Results: We observed a significant increase in distinct bile acids (GCDCA: fold change = 1.41, DCA: fold change = 1.39, GUDCA: fold change = 1.51) following PA supplementation over the study period, with the secondary bile acid DCA displaying a significant negative correlation with the serum cholesterol levels. (4) Conclusions: Oral supplementation with PA modulates the serum metabolome with a particular impact on the circulatory bile acid profile. Since cholesterol and bile acid metabolism are interconnected, the elevation of the secondary bile acid DCA may contribute to the cholesterol-lowering effect of PA.

Additive effect of mesenchymal stem cells and VEGF to vascularization of PLGA scaffolds.

Bone marrow derived mesenchymal stem cells (bmMSCs) are widely used for the generation of tissue engineering constructs, since they can differentiate into different cell types occurring in bone tissues. Until now their use for the generation of tissue engineering constructs is limited. All cells inside a tissue engineering construct die within a short period of time after implantation of the construct because vascularization and establishment of connections to the recipient circulatory system is a time consuming process. We therefore compared the influences of bmMSC, VEGF and a combination of both on the early processes of vascularization, utilizing the mice skinfold chamber model and intravital fluorescence microscopy. Tissue engineering constructs based on collagen coated Poly d,l-lactide-co-glycolide (PLGA) scaffolds, were either functionalized by coating with vascular endothelial growth factor (VEGF) or vitalized with bmMSC. PLGA without cells and growth factor was used as the control group. Functionalized and vitalized tissue engineering constructs showed an accelerated growth of microvessels compared to controls. Only marginal differences in vascular growth were detected between VEGF containing and bmMSC containing constructs. Constructs containing VEGF and bmMSC showed a further enhanced microvascular growth at day 14. We conclude that bmMSCs are well suited for bone tissue engineering applications, since they are a valuable source of angiogenic growth factors and are able to differentiate into the tissue specific cell types of interest. The dynamic process of vascularization triggered by growth factor producing cells can be amplified and stabilized with the addition of accessory growth factors, leading to a persisting angiogenesis, but strategies are needed that enhance the resistance of bmMSC to hypoxia and increase survival of these cells until the tissue engineering construct has build up a functional vascular system.

Perspectives on resorbable osteosynthesis materials in craniomaxillofacial surgery.

Since introduction to the clinics in the 1990s, resorbable osteosynthesis systems have undergone extensive improvements in order to establish their use as a standard treatment, especially in craniomaxillofacial surgery. However, the development of osteosynthesis systems made of poly(α-hydroxy acid) polymers has been hindered by the lack of information on the mechanical properties and biocompatibility of these materials. Moreover, magnesium-based degredable osteosynthesis materials have not yet been integrated into clinical practice owing to biocompatibility problems. Osteosynthesis systems made from nonresorbable titanium alloys have shown excellent biocompatibility, stability and individual fitting to the implant bed, so these materials are currently considered the 'gold standard'. The procedure of plate removal has been subjected to intense scrutiny and controversy. Bioresorbable materials are indicated for special conditions, such as osteosynthesis of the growing skull or orbital floor reconstructions. This paper presents an overview of the currently available and investigated resorbable osteosynthesis materials in comparison with the nonresorbable 'gold standard' titanium. The main problem areas such as sterilization, biocompatibility and stability are highlighted and perspectives for further improvements are provided.

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.

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.

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.

[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.

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.

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.

Micro-computed tomography and histologic evaluation of the interface of hydrogel expander and underlying bone: influence of pressure distributors on bone resorption.

PURPOSE: Tissue expanders lead to changes in the underlying bone and can cause bone resorption. We investigated whether the insertion of mechanical devices that distribute the load on the bone can influence these effects. MATERIALS AND METHODS: A total of 28 Lewis rats were assigned to 1 of 4 groups. Hydrogel expanders were placed subcutaneously either directly on the calvaria, on titanium mesh, or on a titanium plate. The fourth group of rats served as the controls. The bone quality and thickness were assessed beneath, and at the periphery of, the expanders using micro-computed tomography and histologic examination. RESULTS: Micro-computed tomography images were obtained before and 21 days after insertion. The images revealed a significant decrease in hydroxyapatite density beneath the expanders in the group with only expanders. This decrease was reduced with the use of titanium mesh and completely prevented with the use of titanium plates. Histologic examination revealed a significant decrease in bone density and marked lacunae beneath the hydrogel expanders in the group with only expanders. In contrast, the titanium mesh decreased the size of the lacunae, and the titanium plates completely prevented both the formation of lacunae and the decrease in bone thickness. CONCLUSION: The bone resorption caused by hydrogel expanders can be diminished using titanium mesh and completely prevented by the insertion of a titanium plate.

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.

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.

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.

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.