Prognostic importance of mitosis quantification and PHH3 expression in oral epithelial dysplasia

Oral epithelial dysplasia (OED) is diagnosed and graded using a range of histological features, making grading subjective and challenging. Mitotic counting and phosphohistone-H3 (PHH3) staining have been used for the prognostication of various malignancies; however, their importance in OED remains unexplored. This study conducts a quantitative analysis of mitotic activity in OED using both haematoxylin and eosin (H&E)-stained slides and immunohistochemical (IHC) staining for PHH3. Specifically, the diagnostic and prognostic importance of mitotic number, mitotic type and intra-epithelial location is evaluated. Whole slide images (WSI) of OED (n = 60) and non-dysplastic tissue (n = 8) were prepared for analysis. Five-year follow-up data was collected. The total number of mitosis (TNOM), mitosis type and intra-epithelial location was manually evaluated on H&E images and a digital mitotic count performed on PHH3-stained WSI. Statistical associations between these features and OED grade, malignant transformation and OED recurrence were determined. Mitosis count increased with grade severity (H&E: p < 0.005; IHC: p < 0.05), and grade-based differences were seen for mitosis type and location (p < 0.05). The ratio of normal-to-abnormal mitoses was higher in OED (1.61) than control (1.25) and reduced with grade severity. TNOM, type and location were better predictors when combined with histological grading, with the most prognostic models demonstrating an AUROC of 0.81 for transformation and 0.78 for recurrence, exceeding conventional grading. Mitosis quantification and PHH3 staining can be an adjunct to conventional H&E assessment and grading for the prediction of OED prognosis. Validation on larger multicentre cohorts is needed to establish these findings

Heritage branding orientation: The case of Ach. Brito and the dynamics between corporate and product heritage brands

The notion of heritage branding orientation is introduced and explicated. Heritage branding orientation is designated as embracing both product and corporate brands and differs from corporate heritage brand orientation which has an explicit corporate focus. Empirical insights are drawn from an in-depth and longitudinal case study of Ach. Brito, a celebrated Portuguese manufacturer of soaps and toiletries. This study shows how, by the pursuance of a strategy derived from a heritage branding orientation Ach. Brito – after a prolonged period of decline – achieved a dramatic strategic turnaround. The findings reveal how institutional heritage can be a strategic resource via its adoption and activation at both the product and corporate levels. Moreover, the study showed how the bi-lateral interplay between product and corporate brand levels can be mutually reinforcing. In instrumental terms, the study shows how heritage can be activated and articulated in different ways. For instance, it can re-position both product and/or corporate brands; it can be meaningfully informed by product brand heritage and shape corporate heritage; and can be of strategic importance to both medium-sized and small enterprises

Nonperturbative chemical modification of graphene for protein micropatterning

International audienceGraphene's extraordinary physical properties and its planar geometry make it an ideal candidate for a wide array of applications, many of which require controlled chemical modification and the spatial organization of molecules on its surface. In particular, the ability to functionalize and micropattern graphene with proteins is relevant to bioscience applications such as biomolecular sensors, single-cell sensors, and tissue engineering.Wereport a general strategy for the noncovalent chemical modification of epitaxial graphene for protein immobilization and micropatterning. We show that bifunctional molecule pyrenebutanoic acid-succinimidyl ester (PYR-NHS), composed of the hydrophobic pyrene and the reactive succinimide ester group, binds to graphene noncovalently but irreversibly. We investigate whether the chemical treatment perturbs the electronic band structure of graphene using X-ray photoemission (XPS) and Raman spectroscopy. Our results show that the sp2 hybridization remains intact and that the π band maintains its characteristic Lorentzian shape in the Raman spectra. The modified graphene surfaces, which bind specifically to amines in proteins, are micropatterned with arrays of fluorescently labeled proteins that are relevant to glucose sensors (glucose oxidase) and cell sensor and tissue engineering applications (laminin)

X-ray radiation effects in multilayer epitaxial graphene

International audienceWe characterize multilayer graphene grown on C-face SiC before and after exposure to a total ionizing dose (TID) of 12 Mrad(SiO2) using a 10 keV X-ray source. While we observe the partial peeling of the top graphene layer and the appearance of a modest Raman D-peak, we find that the electrical characteristics (mobility, sheet resistivity, free carrier concentration) of the material are mostly unaffected by radiation exposure. Combined with X-ray photoelectron spectroscopy (XPS) data showing numerous carbon-oxygen bonds after irradiation, we conclude that the primary damage mechanism is through surface etching from reactive oxygen species created by the X-rays

Large area and structured epitaxial graphene produced by confinement controlled sublimation of silicon carbide

After the pioneering investigations into graphene-based electronics at Georgia Tech (GT), great strides have been made developing epitaxial graphene on silicon carbide (EG) as a new electronic material. EG has not only demonstrated its potential for large scale applications, it also has become an invaluable material for fundamental two-dimensional electron gas physics showing that only EG is on route to define future graphene science. It was long known that graphene mono and multilayers grow on SiC crystals at high temperatures in ultra-high vacuum. At these temperatures, silicon sublimes from the surface and the carbon rich surface layer transforms to graphene. However the quality of the graphene produced in ultrahigh vacuum is poor due to the high sublimation rates at relatively low temperatures. The GT team developed growth methods involving encapsulating the SiC crystals in graphite enclosures, thereby sequestering the evaporated silicon and bringing growth process closer to equilibrium. In this confinement controlled sublimation (CCS) process, very high quality graphene is grown on both polar faces of the SiC crystals. Since 2003, over 50 publications used CCS grown graphene, where it is known as the "furnace grown" graphene. Graphene multilayers grown on the carbon-terminated face of SiC, using the CCS method, were shown to consist of decoupled high mobility graphene layers. The CCS method is now applied on structured silicon carbide surfaces to produce high mobility nano-patterned graphene structures thereby demonstrating that EG is a viable contender for next-generation electronics. Here we present the CCS method and demonstrate several of epitaxial graphene's outstanding properties and applications

Radiation‐induced osteosarcoma involving the mandible – report of a rare diagnosis

Background Radiation-induced osteosarcomas of the jaws are a rare but often fatal consequence of radiation therapy in the head and neck region. Here we present a case of radiation-induced osteosarcoma of the mandible. Case Presentation A male presented with severe trismus and marked left lingual alveolus expansion 1 year following extractions in the lower left quadrant. Four years previously, he had radical radiotherapy (70Gy) and chemotherapy for a p16-positive T1N2cM0 squamous cell carcinoma of the left tonsil with a positive left level II node. Initial bone biopsies of the left mandible showed a bony sequestrum suggestive of osteoradionecrosis with the presence of abnormal osteoid suspicious of osteosarcoma. Imaging demonstrated an abnormal exophytic bone-forming lesion in the left mandibular body and parasymphysis and ruled out a metastatic lesion. The patient underwent bilateral neck dissection, left mandibulectomy with fibula flap reconstruction and full-thickness skin graft. Conclusions Osteosarcoma should be considered if changes are seen in previously stable irradiated bone with bony destruction and a soft tissue mass. This case highlights the importance of synthesis of clinical, radiological and pathological findings in the diagnosis of such lesions, especially where the histology initially suggested a benign process

Association of C-Reactive Protein With Reduced Forced Vital Capacity in a Nonsmoking U.S. Population With Metabolic Syndrome and Diabetes

OBJECTIVE—A relationship between inflammation, measured by C-reactive protein (CRP), and forced vital capacity (FVC) in diabetes or metabolic syndrome (MetS) has not been established. We investigated whether high CRP is related to reduced FVC in MetS and diabetes

Global lung function initiative 2012 reference values for spirometry in Asian Americans

Background Spirometry reference values specifically designed for Asian Americans are currently unavailable. The performance of Global Lung Function Initiative 2012 (GLI-2012) equations on assessing spirometry in Asian Americans has not been evaluated. This study aimed to assess the fitness of relevant GLI-2012 equations for spirometry in Asian Americans. Methods Asian subjects who never smoked and had qualified spirometry data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2011–2012. Z-scores of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC were separately constructed with GLI-2012 equations for North East (NE) Asians, South East (SE) Asians, and individuals of mixed ethnic origin (Mixed). In addition, Proportions of subjects with observed spirometry data below the lower limit of normal (LLN) were also evaluated on each GLI-2012 equation of interest. Results This study included 567 subjects (250 men and 317 women) aged 6–79 years. Spirometry z-scores (z-FEV1, z-FVC, and z-FEV1/FVC) based on GLI-2012 Mixed equations had mean values close to zero (− 0.278 to − 0.057) and standard deviations close to one (1.001 to 1.128); additionally, 6.0% (95% confidence interval (CI) 3.1–8.9%) and 6.4% (95% CI 3.7–9.1%) of subjects were with observed data below LLN for FEV1/FVC in men and women, respectively. In contrast, for NE Asian equations, all mean values of z-FEV1 and z-FVC were smaller than − 0.5; for SE Asian equations, mean values of z-FEV1/FVC were significantly smaller than zero in men (− 0.333) and women (− 0.440). Conclusions GLI-2012 equations for individuals of mixed ethnic origin adequately fitted spirometry data in this sample of Asian Americans. Future studies with larger sample sizes are needed to confirm these findings

Basic and clinical significance of IGF-I-induced signatures in cancer

The insulin-like growth factor (IGF) system mediates growth, differentiation and developmental processes; it is also involved in various metabolic activities. Deregulation of IGF system expression and action is linked to diverse pathologies, ranging from growth deficits to cancer development. Targeting of the IGF axis emerged in recent years as a promising therapeutic approach in cancer and other medical conditions. Rational use of IGF-I-induced gene signatures may help to identify patients who might benefit from IGF axis-directed therapeutic modalities. In the accompanying research article in BMC Medicine, Rajski et al. show that IGF-I-induced gene expression in primary breast and lung fibroblasts accurately predict outcomes in breast and lung cancer patients