Search

Graphical Abstract:

This article presents a method for the automatic learning of the potentials of a stochastic model, in particular a conditional random field (CRF), in a non-parametric fashion. The proposed model is based on a neural architecture, in order to leverage the modeling capabilities of deep learning (DL) approaches to directly learn semantic and spatial information from the input data. Specifically, the methodology is based on fully convolutional networks and fully connected neural networks. The idea is to access the multiscale information intrinsically extracted in the intermediate layers of a fully convolutional network through the integration of fully connected neural networks at different scales, while favoring the interpretability of the hidden layers as posterior probabilities. The potentials of the CRF are learned through an additional convolutional layer, whose kernel models the local spatial information considered. The loss function is computed as a linear combination of cross-entropy losses, accounting for the multiscale and the spatial information. To evaluate the capabilities of the proposed approach for the semantic segmentation of remote sensing images, the experimental validation was conducted with the ISPRS 2-D semantic labeling challenge Vaihingen and Potsdam datasets and with the IEEE GRSS data fusion contest Zeebruges dataset. As the ground truths of these benchmark datasets are spatially exhaustive, they have been modified to approximate the spatially sparse ground truths common in real remote sensing applications. The results are significant, as the proposed approach obtains higher average classification accuracies than recent state-of-the-art techniques considered in this article. The code is available at https://github.com/Ayana-Inria/CRFNet-RS.

Oral candidiasis is an opportunistic infection of the oral mucosa sustained by fungi of the genus Candida. Various Candida species, with a predominance of C. albicans, normally a saprophyte of the oral cavity, may become virulent and infect the oral mucosa with variegated clinical presentation, in case of imbalance of the oral microbiota, the presence of local predisposing factors and systemic conditions that weaken the immune system. Conventionally, oral candidiasis eradication is done with the help of antifungal drugs. However, the growing phenomena of drug resistance and the increase in infections sustained by non-albicans species being less responsive to common antifungals have orientied researches towards the experimentation of alternative therapies. The present review considered the most promising alternative therapeutic proposals. The use of plant derivatives with phytotherapy is a promising option, such as probiotics, to rebalance the oral microbiota in case of dysbiosis. Finally, antimicrobial photodynamic therapy (aPDT), with highly selective fungicidal activity and free of side effects, is also being studied as a powerful alternative to drug administration. All these therapies are alternatives or supportive to the conventional treatment of recurrent and non-drug-responsive forms of oral candidiasis. However, further studies are needed to define the most active compounds, the efficacy of the therapies compared with the conventional ones, and the planning of regulated and standardized protocols.

Institutional review boards (IRBs) are permitted by regulation to seek assistance from outside experts when reviewing research applications that are beyond the scope of expertise represented in their membership. There is insufficient understanding, however, of when, why, and how IRBs consult with outside experts, as this practice has not been the primary focus of any published literature or empirical study to date. These issues have important implications for IRB quality. The capacity IRBs have to fulfill their mission of protecting research participants without unduly hindering research is influenced by IRBs’ access to and use of the right type of expertise to review challenging research ethics, regulatory, and scientific issues. Through a review of the regulations and standards permitting IRBs to draw on the competencies of outside experts and through examination of the needs, strategies, challenges, and concerns related to doing so, we identify critical gaps in the existing literature and set forth an agenda for future empirical research.

New federal rules require researchers to submit plans for how to manage and share their scientific data, but institutional ethics boards may be underprepared to review them.

Human research protection programs (HRPP) generate an abundance of data on performance, capacity, and compliance. When used effectively, this information can be instrumental in helping HRPPs meet programmatic and institutional goals, demonstrate growth and success, and improve the HRPP overall. Metrics must be grounded in professional insight so that HRPPs can pair analytics with strategies for future action or improvement. The purpose of this paper is to demonstrate how high‐performing HRPPs develop, adopt, and implement a metrics framework that benefits everyday operations and produces real‐world results. Through a three‐part thematic framework (of insight, data, and action) and by providing case examples and actionable strategies, this article will address how HRPPs iteratively develop and characterize their metrics, build a metrics framework that leverages both quantitative and qualitative data to validate outcomes, and activate human insight to produce meaningful communication, visualization, and dissemination of data.

The understanding of how spins move and can be manipulated at pico- and femtosecond timescales has implications for ultrafast and energy-efficient data-processing and storage applications. However, the possibility of realizing commercial technologies based on ultrafast spin dynamics has been hampered by our limited knowledge of the physics behind processes on this timescale. Recently, it has been suggested that inertial effects should be considered in the full description of the spin dynamics at these ultrafast timescales, but a clear observation of such effects in ferromagnets is still lacking. Here, we report direct experimental evidence of intrinsic inertial spin dynamics in ferromagnetic thin films in the form of a nutation of the magnetization at a frequency of ~0.5?THz. This allows us to reveal that the angular momentum relaxation time in ferromagnets is on the order of 10?ps.

Background: West Syndrome is a rare epileptic encephalopathy involving infantile spasms, altered electroencephalographic pattern with hypsarrhythmia, and psychomotor development delay. It arises in paediatric patients, generally within the first year of life, in symptomatic or idiopathic form depending on the presence of hereditary features or not. Case Report: In this report it is described the case of a West syndrome patient affected by multiple caries, gingival enlargement, dental eruption abnormalities, high-arched palate and MIH, treated at the dental clinic of University of Bari “Aldo Moro”. Discussion: West patients present with multiple oral abnormalities, including altered eruption timing, teeth agenesis, teeth shape and position abnormalities, plaque and calculus accumulation, malocclusions and bad oral habits (mouth breathing, nails biting). Conclusion: West Syndrome patients’ oral hygiene is generally bad due to their motor difficulty and to their low compliance towards dentists, which entails general anaesthesia to perform dental treatment. West Syndrome pharmacological treatment is usually based on antiepileptic drugs and/or ACTH. These medications are well known for their ability to induce gingival enlargement, increasing the possibility of plaque accumulation and gingivitis development.

Introduction:Transplantation is a field with unique medical and administrative challenges that involve an equally diverse array of stakeholders. Expectantly, the litigation stemming from this field should be similarly nuanced. There is a paucity of comprehensive reviews characterizing this medicolegal landscape. Design:The Caselaw Access Project Database was used to collect official court briefs of 2053 lawsuits related to kidney, liver, heart, lung, and pancreas transplantation. A thematic analysis was undertaken to characterize grounds for litigation, defendant type, and outcomes. Cases were grouped into policy, discrimination, poor or unsuccessful outcome, or other categories. Results:One hundred sixty-four court cases were included for analysis. Cases involving disputes over policy coverage were the most common across all organ types (N = 55, 33.5%). This was followed by poor outcomes (N = 51, 31.1%), allegations of discrimination against prison systems and employers (N = 37, 22.6%) and other (N = 21, 12.8%). Defendants involved in discrimination trials won with the greatest frequency (N = 29, 90.62%). Defendants implicated in policy suits won 65.3% (N = 32), poor outcomes 62.2% (N = 28), and other 70% (N = 14). Of the 51 cases involving poor outcomes, plaintiffs indicated lack of informed consent in 23 (45.1%). Conclusion:Reconsidering the informed consent process may be a viable means of mitigating future legal action. Most discrimination suits favoring defendants suggested previous concerns of structural injustices in transplantation may not be founded. The prevalence of policy-related cases could be an indication of financial burden on patients. Future work and advocacy will need to substantiate these concerns and address change where legal recourse falls short.

Heterogeneous treatment effects represent a major issue for medicine as they undermine reliable inference and clinical decision-making. To overcome the issue, the current vision of precision and personalized medicine acknowledges the need to control individual variability in response to treatment. In this paper, we argue that gene-treatment-environment interactions (G × T × E) undermine inferences about individual treatment effects from the results of both genomics-based methodologies—such as genome-wide association studies (GWAS) and genome-wide interaction studies (GWIS)—and randomized controlled trials (RCTs). Then, we argue that N-of-1 trials can be a solution to overcome difficulties in handling individual variability in treatment response. Although this type of trial has been suggested as a promising strategy to assess individual treatment effects, it nonetheless has limitations that limit its use in everyday clinical practice. We analyze the existing variability within the designs of N-of-1 trials in terms of a continuum where each design prioritizes epistemic and pragmatic considerations. We then support wider use of the designs located at the pragmatic end of the explanatory-pragmatic continuum.

Lipid metabolic changes in cancer are attracting increased attention. BAFF/APRIL axis is a multifaceted immune regulator of adipose tissue function and an emerging target for anti-BCMA therapy in multiple myeloma (MM). However, lipid analyses are scarce in MM onset and response to treatment.

Thiopurines are commonly used in the maintenance of remission for children with inflammatory bowel diseases (IBDs). Variation in drug metabolism may affect hepatotoxicity or therapeutic effect. We aimed to describe our center's experience with thiopurine optimization through the use of reduced thiopurine dosing in combination with allopurinol upon hepatotoxicity, drug metabolite levels, and clinical outcomes in children with IBD. Patients aged 2 to 21 years with IBD treated with the combination of thiopurines/allopurinol between 2008 and 2015 were retrospectively reviewed. Patients previously treated with antitumor necrosis factor therapy were excluded. Demographic data, transaminase levels (aspartate transaminase, alanine transaminase), drug metabolites levels (6-thioguanine [6-TG], 6-methylmercaptopurine), physician global assessment, and corticosteroid use were recorded at baseline, 6, and 12 months. Fifty-two patients (29 girls, 56%) met inclusion criteria. Thirty-two of 52 (62%) remained on the combination for 12 months. In those remaining on the thiopurine/allopurinol combination, median alanine transaminase and aspartate transaminase levels were reduced (P< 0.001) and median 6-TG levels were increased (P< 0.001) at both 6 and 12 months. Corticosteroid use was decreased at both 6 (P< 0.001) and 12 months (P< 0.001) compared to use at baseline. Remission rates also improved at both 6 (P= 0.013) and 12 months (P= 0.003). Twenty of the 52 patients (38%) had discontinued the thiopurine/allopurinol combination within 12 months of initiation with 17 of 52 (33%) initiating antitumor necrosis factor therapy. Low-dose thiopurines in combination with allopurinol improved hepatotoxicity and increased 6-TG levels in children with IBD. Corticosteroid use was reduced and remission rates improved in those patients remaining on this combination for 1 year. However, approximately 40% of patients required a change in therapy within 12 months.

Background: To present the outcomes for a case of unilateral mandibular subcondylar fracture with dislocation in an 11-year-old female treated with an acrylic splint for functional repositioning of the mandible.Clinical presentation: A splint was placed in the upper arch to restore the functional repositioning of the mandible. The splint’s height was increased up to 5.5 mm on the side of the fracture to stimulate growth on the deficient side. To correct the mandibular asymmetry, a construction bite was made by 4 mm advancing. The total treatment time was 16 months. Long-term five-year follow up showed complete healing. A portion of the ramus appeared lateral with respect to the condylar head, whereas the mandibular deviation to the right side was fully corrected.Conclusion: Conservative treatment may be an appropriate method for children in select cases, as they have an increased potential for spontaneous regeneration.

(Abstracted from Contraception, https://doi.org/10.1016/j.contraception.2019.04.004)Globally, nearly half of pregnancies are unintended. Sociodemographic factors associated with unintended pregnancy include age, parity, education, and economic status.

To enhance shared decision-making for patients with breast cancer, we developed an evidence-based educational breast cancer video (BCV) providing an overview of breast cancer biology, prognostic indicators, and surgical treatment options while introducing health care choice. By providing patients access to a BCV with information necessary to make informed surgical decisions before seeing a surgeon, we aimed to increase patient participation in the decision-making process, while decreasing distress. Patients with a new diagnosis of breast cancer were provided a link to the BCV. Group 1 participated in online pre- and postvideo questionnaires, with the BCV embedded in between. The questionnaires evaluated self-reported baseline knowledge of breast cancer and perceived distress related to the diagnosis. Changes in self-reported responses were analyzed using the Wilcoxon matched pairs test. Group 2 received a survey collecting demographics, decision-making information, and perceptions of the BCV at the time of clinic visit before meeting the surgeon. Group 1 included 69 subjects with 62 per cent reporting improved knowledge and 30 per cent reporting reduced distress in regard to their breast cancer diagnosis. Group 2 included 87 subjects; 94 to 98 per cent felt the BCV provided information and stimulated thoughts and questions to assist in breast cancer treatment decision-making. The BCV was positively received by participants and feasible to implement into clinical practice. Evidence-based media tools improve knowledge and reduce distress in patients with a new diagnosis of breast cancer as well as contributing to the shared decision-making process.

This article reports on a successful project for 3D imaging research, digital applications, and use of new technologies in the museum. The article will focus on the development and implementation of a viable workflow for the production of high-quality 3D models of museum objects, based on the 3D laser scanning and photogrammetry of selected ancient Egyptian artefacts. The development of a robust protocol for the complete process chain for imaging cultural heritage artefacts, from the acquisition of 2D and/or 3D images to the development of interactive applications for the public audience, was a specific objective of the project. The workflow devised by the university museum team combines reference photography and 3D imaging with a curatorial review of the actual object to its digital counterpart. It also integrates methodologies for managing the accompanying metadatasets to record these activities. As final stage deliverables from the process, the museum is making high-quality 3D images of artefacts from its collection available through creation and dissemination of digital 3D multiplatform interactive applications in order to allow remote access and to enhance the museum's public engagement. This short article concludes with practical considerations for a 3D imaging workflow such as time and skills needed, 3D model quality, and expectation management.

We consider an hysteresis model recently proposed, where the magnetic constitutive law M(H) is derived from considerations on domain wall motion. For this model we show that it is possible to build up the inverse constitutive law H(M), exactly. The inverse constitutive relation is applied to one-dimensional numerical computation of flux distributions and eddy currents in a magnetic slab.

Background: The prognosis of the oral squamous cell carcinoma (OSCC) patients remains very poor, mainly due to their high propensity to invade and metastasize. E-cadherin reduced expression occurs in the primary step of oral tumour progression and gene methylation is a mode by which the expression of this protein is regulated in cancers. In this perspective, we investigated E-cadherin gene (CDH1) promoter methylation status in OSCC and its correlation with Ecadherin protein expression, clinicopathological characteristics and patient outcome. ; Methods: Histologically proven OSCC and paired normal mucosa were analyzed for CDH1 promoter methylation status and E-cadherin protein expression by methylation-specific polymerase chain reaction and immunohistochemistry. Colocalization of E-cadherin with epidermal growth factor (EGF) receptor (EGFR) was evidenced by confocal microscopy and by immunoprecipitation analyses. ; Results: This study indicated E-cadherin protein down-regulation in OSCC associated with protein delocalization from membrane to cytoplasm. Low E-cadherin expression correlated to aggressive, poorly differentiated, high grade carcinomas and low patient survival. Moreover, protein down-regulation appeared to be due to E-cadherin mRNA downregulation and CDH1 promoter hypermethylation. In an in vitro model of OSCC the treatment with EGF caused internalization and co-localization of E-cadherin with EGFR and the addition of demethylating agents increased E-cadherin expression. ; Conclusion: Low E-Cadherin expression is a negative prognostic factor of OSCC and is likely due to the hypermethylation of CDH1 promoter. The delocalization of E-cadherin from membrane to cytoplasm could be also due to the increased expression of EGFR in OSCC and the consequent increase of E-cadherin co-internalization with EGFR.

Oral candisosis is an heterogeneous group of diseases, caused by different species of Candida fungus. The incidence of drug-resistant species is increasing dramatically; furthermore, in recent years higher incidences of non-albicans and antimycotic-resistant species of Candida have been reported, thus increasing necessity of a non-antibiotic agent, which should be both highly effective and safe. It has been showed that the main polyphenols component of green tea, epigallocatechin-gallate (EGCG), has antibacterial activity; recently, it has been reported its antifungal activity too. We tested the effectiveness of a 0.20% EGCG (TEAVIGO®) gel, a non-pharmaceutical product suitable for oral in vivo use, on four species of Candida yeast (C.albicans, Cparapsilosis, C.tropicalis, C.glabrata), evaluating its antifungal activity and its capacity to inhibit biofilm formation. The EGCG gel showed a remarkable activity against C. parapsilosisand C. tropicalis.This preliminary study confirms EGCG effectiveness on fungi; for this reason, a product with such a low concentration of EGCG could be used with no side-effect for every-day oral hygiene. Anyway, mechanisms of antifungal activity of EGCG are not comprehended and need further studies to better understand the reasons of some Candida species' resistance.

Some species of Candida are opportunistic pathogens that can cause disease in a host immunocompromised by underlying local or systemic pathological processes. C. albicansis the species most often associated with oral lesions, but other species of Candida, including C. glabrata, C. tropicalisand C. parapsilosis, have also been isolated in the saliva of subjects with and without candidiasis. In the present study we evaluated the host defence mechanisms induced by Candida albicansand other Candida species in monocytes and oral epithelial cells in order to establish the existence of a species-specific cellular response. Our results indicated that, during Candida species infection, the epithelial cells actively participate in the host defence by producing antimicrobial peptides and proinflammatory cytokines. Moreover, in infections caused by Candida tropicalisand Candida glabrata, the host defence may be strengthened by the release of perforin and granzyme by polymorphonuclear leukocytes recruited at the site of infection.

The EGFR (epidermal growth factor receptor) a member of the family of transmembrane protein kinase receptors known as the erbB family shows a significant correlation with the presence of metastases and poorly differentiated oral cancer. Aim of the present work is to define the key-role of EGFR in oral cancer prognosis. We have analyzed the EGFR expression on 149 cases of oral squamous cell cancers (OSCC) and we have found that it was poorly expressed in normal oral epithelium, but its expression was significantly increased in OSCCs. Moreover, we have recorded that both pEGFR-Tyr 845 and pEGFR-Tyr 1068 were mainly distributed in high histological grading and in advanced stages. Western blotting has confirmed the total absence of EGFR phosphorylation in normal oral epithelium and the higher level of protein phosphorylation in representative cases of OSCCs. The EGF-R amplification was found by fluorescence in situ hybridization (FISH) in 14% of OSCC; interestingly, EGF-R amplification was mainly observed in OSCC with higher histological grading (G2 and G3) and advanced stage (pT4) sub-groups. Kaplan-Meyer survival analysis suggested that patients with positive pEGFR-Tyr 845 tumors had a worse prognosis and were bad responders to chemotherapy. These results confirm the central role of EGF-R activation status as a prognostic biomarker in OSCC.

Oral Squamous Cell Carcinoma (OSCC) is the sixth most frequent malignant tumour. There is some evidence that tongue cancer has a higher local failure rate and poorer prognosis than other anatomical sites in the oral cavity. We used tongue squamous cell carcinoma cell lines harbouring mutated p53/p16 as tongue cancer models to study the influences exerted by p53 and p16 genes on the expression of micro RNAs (miRNAs). The study was performed on microarray chips harbouring 298 miRNA sequences. OSCC cell lines used in this study were SCC-4, SCC-15 and SCC-25, all three carrying mutated/hypermethylated p53/p16. The expression values normalized to healthy control of 298 miRNAs were obtained for each cell line. MiRNA 196b was found hyperexpressed in the three cell lines. MiRNAs 19b-1, 21, 27a, 30d, 134, 339, 379 and 465 were found altered in two out of three cell lines. miRNAs found altered in one cell line out of three were: 7b, 23a, 25, 30c, 30e-3p, 107,125b, 124a, 214, 216, 325 and 384. A literature review for each miRNA found significant was undertaken. Some miRNAs have a well-known role in oral cancer, some have been put in correlation with other cancers/diseases, others are found significant for the first time. These early results in tongue cancer cell lines harbouring mutation of p16/p53 need further analyses to understand whether this variation of miRNA levels are directly influenced by the malfunction of these proteins or if, vice-versa, altered miRNA levels influence the function of p16 and p53.

This paper focuses on the classification of multichannel images. The proposed supervised Bayesian classification method applied to histological (medical) optical images and to remote sensing (optical and synthetic aperture radar) imagery consists of two steps. The first step introduces the joint statistical modeling of the coregistered input images. For each class and each input channel, the class-conditional marginal probability density functions are estimated by finite mixtures of well-chosen parametric families. For optical imagery, the normal distribution is a well-known model. For radar imagery, we have selected generalized gamma, log-normal, Nakagami and Weibull distributions. Next, the multivariate d-dimensional Clayton copula, where d can be interpreted as the number of input channels, is applied to estimate multivariate joint class-conditional statistics. As a second step, we plug the estimated joint probability density functions into a hierarchical Markovian model based on a quadtree structure. Multiscale features are extracted by discrete wavelet transforms, or by using input multiresolution data. To obtain the classification map, we integrate an exact estimator of the marginal posterior mode.

The oral cavity is home to numerous viruses and micro-organisms recognized as having a role in various oral diseases as well as in infections in other parts of the body. Indeed, in general a microbial infection underlies or is believed to underlie the ample spectrum of oral diseases, from tooth enamel decay to periodontal lesions, from candidiasis to virus-induced oral squamous cell carcinomas, and bullous autoimmune oral disorders. This clinico-pathological context stresses the need of targeted therapies to specifically kill infectious agents in a complex environment such as the oral cavity, and explains the current interest in exploring peptide-based therapeutic approaches in oral and dental research. Here, we review the therapeutic potential of antimicrobial peptides such as LL-37, beta defensins, adrenomedullin, histatins, and of various peptides modulating gene expression and immuno-biological interaction(s) in oral diseases.

Previous studies have demonstrated that patients affected by Oral Lichen Plauns (OLP) show lower levels of salivary fibronectin when compared with normal controls. Similarly, tissutal fibronectin expression is lost in epidermal basal layer and papillary dermis of OLP patients. To date, no data exist on the potential role of Plasma Fibronectin(PFn) in OLP pathogenesis, diagnosis and treatment. The objectives of the present study are: a) to determine the PFn levels in OLP patients; b) to evaluate a possible association between OLP clinical form and PFn levels; and c) to determine the PFn levels in relation to OLP signs and symptoms treatment. Twenty consecutive patients affected by OLP were enrolled. All patients were treated for eight weeks with topical clobetasol 0.05%. OLP signs and symptoms were scored before and after treatment. PFn level was determined by a nephelometric system. OLP signs and symptoms significantly improved after treatment. The mean levels of PFn were 31.84mg/dL at the beginning and 26.76mg/dL at the end of the study. The difference was not statistically significant (p=0.60). PFn in OLP patients remains in normal value range. OLP clinical form does not influence the PFn levels. Amelioration of symptoms and signs of atrophic-erosive and reticular OLP are induced by clobetasol treatment and the PFn seems not to interfere in the healing processes induced by topical corticosteroid. In contrast to what is observed in traumatic or diabetic wound healing, levels of PFn do not promote OLP lesion healing. PFn is not to be considered as a marker of OLP disease activity and its role in OLP pathogenesis still remains unclear.

Oncogenic HPVs are necessarily involved in cervical cancer but their role in oral carcinogenesis is debated. To detect HPV in oral cancer, 38 cases of formalin fixed-paraffin embedded OSCC were studied by both DNA genotyping (MY09/11 L1 consensus primers in combination with GP5-GP6 primer pair followed by sequencing) and immunohistochemistry (monoclonal Abs against capsid protein and HPV-E7 protein, K1H8 DAKO and clone 8C9 INVITROGEN, respectively). HPV-16 tonsil cancer was used as positive control. The overall prevalence of HPV infection in OSCCs was 10.5%. Amplification of DNA samples showed single HPV DNA infection in 3 cases (HPV16; HPV53; HPV70) and double infection in one case of cheek cancer (HPV31/HPV44). The overall HR-HPV prevalence was 7.5%. E-7 antigen was immunohistochemically detected in all HPV-positive cases. HPV+ OSCC cases showed an overall better outcome than HPV negative oral cancers, as evaluated by Kaplan-Meier curves. HPVs exert their oncogenic role after DNA integration, gene expression of E5, E6 and E7 loci and p53/pRb host proteins suppression. This study showed that HPV-E7 protein inactivating pRb is expressed in oral cancer cells infected by oncogenic HPV other than classical HR-HPV-16/18. Interestingly HPV-70, considered a low risk virus with no definite collocation in oncogenic type category, gives rise to the expression of HPV-E7 protein and inactivate pRb in oral cancer. HPV-70, as proved in current literature, is able to inactivates also p53 protein, promoting cell immortalization. HPV-53, classified as a possible high risk virus, expresses E7 protein in OSCC, contributing to oral carcinogenesis. We have identified among OSCCs, a subgroup characterized by HPV infection (10.5%). Finally, we have proved the oncogenic potential of some HPV virus types, not well known in literature.

The aim of this study is to investigate the expression of the chromosomal passenger protein Aurora B and its activated (phosphorylated) form in a large series of human oral squamous cell cancers (OSCC) and to evaluate its clinical and prognostic significance. Western blotting analysis revealed overexpression of both Aurora B and Thr-232 Phopsho-Aurora B in OSCC lines as compared to normal keratinocytes and bladder cancer cells. Furthermore, protein expression was analysed by immunohistochemistry in 101 OSCC of different site, stage and histological grade and in normal peritumoural areas. The intracellular localization of Aurora B in tumour cells was mainly nuclear, especially in proliferative areas, and significant overexpression was found in tumours in comparison to normal peritumoural areas (P=0.012). Staining results were correlated with clinicopathological parameters and long-term follow-up, and a significant association was found between protein expression and tumour stage (stage II, III and IV vsstage I, P=0.030) and size (<2cm vs>2cm, P=0.010). Cox regression analysis confirmed a poorer disease-free survival in cases with high expression of Aurora B protein. Kaplan-Meier curves showed shorter time to progression in patients with high levels of Aurora B expression (p<0.05). Moreover, the tumoral group with nuclear Aurora B immunolocalization had the worst prognosis (P=0.0364 in disease free survival). Our results suggest that assessing Aurora B expression might help in patients' risk stratification and serve as a novel therapeutic target in advanced OSCCs.

Herpes labialis are the most frequent clinical manifestations of HSV-1 infection. Epithelial cells are able to respond to HSV-1 presence inducing the expression of IL-6, IL-1, TNF-α and IL-8. These proinflammatory cytokines have a function in the acute-phase response mediation, chemotaxis, inflammatory cell activation and antigen-presenting cells. In the human epithelial cell models, it has been demonstrated that, after an early induction of proinflammatory host response, HSV-1 down-modulates the proinflammatory cytokine production through the accumulation of two viral proteins, ICP4 and ICP27, whose transcription is induced by tegument protein VP16. These viral proteins, through the decreasing of stabilizing the mRNAs of proinflammatory genes, delay cytokine production to an extent that allows the virus to replicate. Moreover, viral transactivating proteins, ICP-0 and VP-16 induce IL-10 expression. The conventional treatment of herpes labialis involves the topical and systemic use of antiviral drugs but it is necessary to find new therapies that can act in a selective and non-cytotoxic manner in viral infection. Laser diode therapy has been considered as a non-invasive alternative treatment to the conventional treatment of herpes labialis in pain therapy, in modulation of inflammation and in wound healing. This study aims to report a possible mechanism of action of laser diode irradiation in prevention and reduction of severity of labial manifestations of herpes labialis virus. We investigated, in an in vitromodel of epithelial cells HaCat, the laser-effect on HSV-1 replication and we evaluated the modulation of expression of certain proinflammatory cytokines (TNF-α, IL-1β and IL-6), antimicrobial peptide HBD2, chemokine IL-8 and the immunosuppressive cytokine, IL-10. Our results lead us to hypothesize that LD-irradiation acts in the final stage of HSV-1 replication by limiting viral spread from cell to cell and that laser therapy acts also on the host immune response unblocking the suppression of proinflammatory mediators induced by accumulation of progeny virus in infected epithelial cells.

Thymomas are rare tumors, which can be associated to a variety of paraneoplastic syndromes, including a fatal hypogammaglobulinemia, namely Good's Syndrome (GS). Although the combination of thymoma and hypogammaglobulinemia is regarded as sufficient for diagnosis of Good's syndrome, some thymoma patients with a clear clinical picture of immunodeficiency present normal levels of immunoglobulins. We describe the case of a patient, with a 20-year history of thymoma, who underwent several operations and lines of chemotherapy, and suffered from recurrent infections, including one rare skin infection from Pseudoallescheria boydii. The patient constantly presented normal levels of gammaglobulins.

Photodynamic therapy (PDT) is a selective modality of killing targeted cells, mostly known for its application in neoplasms. PDT can be considered to be an alternative method for the elimination of periodontal bacteria from the pocket without harms for the resident tissues. Therefore, PDT may replace systemic antibiotics and enhance the effect of mechanical treatments of periodontal defects. This effort focused on the in vitrosensitization of periopathogens (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatumand Prevotella intermedia) Toluidine Blue mediated and on the use of a Diode laser emitting source. The objective of this research was to evaluate the bactericidal in vitroeffect of laser diodes 830 nm (as the light source) after photosensitization with Toluidine Blue (TBO) on the following periopathogenic bacteria: Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatumand Prevotella intermedia. After evaluating the effect on the single bacterial strain, the ability of Diode Laser to disrupt the structure of biofilms produced by A. actinomycetemcomitansafter photosensitization with TBO was also analyzed. The study suggests that the association of TBO and diode laser light 830 nm is effective for the killing of bacteria strains and determines the photoinactivation of Aggregatibacter biofilms. In summary, photodynamic therapy has effectively shown its capabilities and, therefore, it can be considered a valid alternative approach to antimicrobial therapy of periodontitis.

Human papillomavirus (HPV) 16 E7 gene product encodes the major transforming activity of the virus so as to induce neoplastic transformation. Continued expression of HPV16 E7 protein is required for both the establishment and maintenance of the transformed cellular phenotype. Therefore, understanding of the molecular and biochemical factors leading to the expression of E7 protein is important in relation to HPV-associated diseases. Previously, we identified a rare codon usage and a specific interaction between cytokeratin (CK) 7 and HPV16 E7 mRNA as factors modulating HPV16 E7 expression. In the present study we report that CK19, a biochemical marker of squamous oral and cervical cancer carcinogenesis, promotes the expression of HPV16 E7 oncoprotein by binding to the CK792–97SEQIKA peptide. These findings shed light on the dynamic functionality of the intermediate filament cytoskeleton, open new perspectives for investigating the role of CKs in controlling HPV16 E7 expression, and suggest new therapeutic avenues for HPV-associated carcinomas.

Stick-Slip motion is the basis for the description of a great variety of phenomena characterized by the presence of sliding friction between bodies with elastic features. In this article a simple experimental equipment for the analysis of this kind of dynamics is described. A wide set of possible experimental observations and measures are presented. This equipment has been tested at the university of Napoli Federico II in courses for undergraduate students and in the teacher training school for secondary education.

The complex pathophysiology of human immunodeficiency virus (HIV) infection and the relatively high mutation rate of the retrovirus make it challenging to design effective anti-HIV vaccines. Several attempts have been made during the last decades to elucidate the enigmatic immunology of HIV infection and to predict potential immunogenic peptides for active vaccination using bioinformatic analysis methods. The results obtained to date to address this important problem are scarce. In this study, we exploit available HIV databases and analyse previously characterized HIV-encoded linear B-cell epitopes for their amino acid sequence similarity to the human or murine host proteome. We obtained further documentation that the HIV-derived antibody-targeted sequences mostly coincide with peptide areas rarely shared with the host proteins. In toto, our past and present data give clear-cut support to the statement that low-similarity to the host proteome is a major mechanism in defining viral peptide immunogenicity and indicate a possible way for inducing effective, high-titer, and non-cross-reactive antibodies to be used in anti-HIV vaccine therapy.

In an attempt to understand the molecular factors underlying squamous cell carcinogenesis in HPV-infected oral and cervical tissues, we examined the Sp3-dependent cytokeratin expression in HPV-positive CaSki cells. Two sets of cytokeratins were examined: the simple epithelial CK 7, 8, 18, 19, and 20, which are generally expressed in simple epithelia and CK4, 10, 13, and 17, which are expressed in squamous epithelia. Two additional CK pairs, i.e. CK6/CK16 and CK4/CK13 were analyzed as controls of the proliferation/differentiation cell status, respectively. We report that Sp3 gene silencing specifically hits CK18 and CK19, which are markers of oral and cervical squamous tumors. These data may be of help in immunopathological definition of squamous carcinogenesis.

Contrary to early beliefs, celiac disease (CD) is relatively common; however, it still remains underdiagnosed since most cases are atypical, with few or no gastrointestinal symptoms and predominance of extraintestinal manifestations. As a consequence, the diagnosis of the disorder often requires a multidisciplinary approach. Also some oral ailments have been described in celiac patients. In this study, we review the papers that have reported oral manifestations in subjects with CD.

Squamous cell carcinoma (SSC) is the most frequent malignant tumor of the oral cavity. A study on the effect of all-trans retinoic acid (RA) on cell growth, expression of GRIM-19 and content and activity of complex I of the mitochondrial respiratory chain in normal human keratinocytes (NHEK) and mouth carcinoma cells with low (HN) and high (KB) transformation grade was carried out. In NHEK cells, RA treatment resulted in growth suppression, significant overexpression of GRIM-19 protein, enhanced content of complex I but depressed activity of NADH-UQ oxidoreductase activity of the complex. In HN cells, RA treatment depressed cell growth, inhibited the enzymatic activity of complex I but had no significant effect on the levels of GRIM-19 and complex I. In KB cells RA had no effect on cell growth, GRIM-19 expression, content and activity of complex I.

Oral lichen planus (OLP) is a relatively common disorder whose cause is still unknown. It occurs mostly on the buccal mucosa, but the gingivae, tongue, floor of the mouth and retromalar pads may also be affected. It rarely occurs on the lips and usually in association with oral lesions. We report a case series of ten patients with a history of isolated swelling of the lower and/or upper lip, erosions and crusting. General medical history, examination of the oral cavity and recording of signs and symptoms were carried out for each patient. Among the six different clinical variants of OLP described by Andreasen, the atrophic-erosive form was the most common in the course of isolated LP of the lip in our series. Five cases presented HCV hepatitis. A complete remission of lesions was observed in eight patients after topical treatment with clobetasol propionate 0.05% and tocopherol oil, while partial improvement was noted in those remaining. Isolated LP of the lip is unusual and presents a diagnostic challenge, however an appropriate differential diagnosis is fundamental. Lesions of the lips might represent a more or less precocious phase of oral involvement. Moreover the reasons for the unique localization on the lips need to be explored. Several variables, including age, duration of lesions, concomitance of other diseases, and genetic predisposition may be involved. Isolated LP of the lip is a well-known condition which responds well to topical treatment with corticosteroids. A thorough medical management and active early treatment are necessary to improve symptoms and might also be a relevant prevention strategy from squamous cell carcinoma risk, although data to fully support this statement still need investigation.

COX-2 expression in tumour cells has been associated with carcinogenesis in many human neoplasms, including head and neck cancer, while the COX-1 isoform of the cyclooxygenase enzyme is constitutively expressed in normal tissues. We measured COX-1 and COX-2 m-RNA expression in samples of both oral cancer and matched oral mucosa from 22 patients by RealTime RT-PCR; clinic pathological data (grading, TNM staging, inflammation, follow-up) of all patients were available for statistical evaluation. Most of the tumor samples in our study expressed at least one cyclooxygenase enzyme (COX-1 or COX-2 mRNA) more than their matched normal oral mucosa (p<0.05), with no correlation with the entity of inflammation, and a significant inverse relationship was found between COX-1 and COX-2 in each sample. Higher levels of COX-2 expression were associated with poor disease-free survival (p<0.05), but not with overall survival and higher tumor stage and grade. Our results suggest that COX-1 may play a role in oral carcinogenesis, and could be regarded as a potential therapeutic target by chemo preventive drugs; moreover, COX-2 expression might be addressed as a new prognostic tool in the clinical management of OSCC.

Background:Lichen planus with simultaneous oral and genital involvement in males is a quite rare condition and often difficult to diagnose. The prevalence, treatment options, and management for this condition are far from being established, and research in this area primarily relies on anecdotes. We present the clinical features of eight cases of peno‐gingival lichen planus and propose a management algorithm for this condition based on the best available published evidence. Methods:Personal medical history was collected for all cases. Following careful examination of the oral and genital mucosae, pathology was obtained, previous treatments and duration of mucosal lesions ascertained, treatment initiated, and response evaluated at 8 weeks on both oral and genital lesions. The first‐line drug was topical clobetasol propionate 0.05% cream in all cases; in case of failure, topical cyclosporin was used. A review of the literature on treatment options for this rare condition was performed based upon standard literature review practices. Results:Five cases presented gingival lesions that clinically resembled lichen planus. Glans penis was involved in all patients. All patients responded to treatment except for one. Oral candidiasis was the only observed side effect. Conclusions:Genital lichen planus may be suspected in males when atrophic‐erosive gingival lichen planus is found. A thorough multidisciplinary medical management and active early treatment are necessary to improve symptoms and prevent genital sequelae and, given the risk of squamous cell carcinoma, as a preventative strategy, although this area still needs investigation. Therapeutic trials relating to the treatment of peno‐gingival lichen planus may be undertaken considering that current management relies exclusively on observations of case reports.

Squamous cell carcinoma (SCC) of the lip is a relatively common malignancy of the head and neck region. Tumour thickness, grading and perineural invasion are significant prognostic indicators. However, there is still the need of new reliable biological markers able to predict the prognosis of the single cases with an unfavourable biological behaviour unpredictable by the classic clinical-pathological parameters. 32 cases of (SCC) of the lower lip were analysed for their clinicopathologic features, and immunohistochemical expression of Fas/FasL in neoplastic cells and in inflammatory infiltrate. Moreover the density and phenotype of tumour-infiltrating lymphocytes (TIL) were analysed. The results were related with the follow-up of the patients ranging from 2 to 6 years. The cases with over-expression of Fas/FasL in neoplastic cells and Fas+ in T cells preferentially showed a more aggressive clinical behaviour (p<0.01). Moreover we found an alteration of the normal expression of CD4 and CD8 lymphocyte types in ten cases. This data suggest that the Fas/FasL pathway is involved in the close relation between neoplastic cells and T cells and so in the biological behaviour of these tumours.