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Anaplastic lymphoma kinase (ALK) rearrangements represent the molecular driver of a subset of non-small cell lung cancers (NSCLCs). Despite the initial response, virtually all ALK-positive patients develop an acquired resistance to the ALK inhibitor crizotinib, usually within 12 months. Several next-generation ALK inhibitors have been developed in order to overcome crizotinib limitation, providing an unprecedented survival for this subset of patients. The aim of this review to summarize the current knowledge on ALK tyrosine kinase inhibitors (TKIs) in the treatment of advanced ALK-positive NSCLC, focusing on the role of novel ALK inhibitors in this setting. In addition, we will discuss their role in the pharmacological management of ALK-positive brain metastasis. Next-generation ALK inhibitors showed an impressive clinical activity in ALK-positive NSCLC, also against the sanctuary site of CNS. Sequential therapy with ALK TKIs appears to be effective in patients who fail a first ALK TKI and translates in clinically meaningful benefit. However, these agents display different activity profiles against crizotinib resistance mutation; therefore re-genotyping the disease at progression in order to administer the right TKI to the right patient is going to be necessary to correctly tailor the treatment. To avoid repeated invasive procedure, noninvasive methods to detect and monitor ALK rearrangement are under clinical investigation.

Glioblastoma multiforme (GBM) is the most malignant brain tumor and is associated with poor prognosis due to its thorny localization, lack of efficacious therapies and complex biology. Among the numerous pathways driving GBM biology studied so far, PTEN/phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) signaling plays a pivotal role, as it controls cell survival, proliferation and metabolism and is involved in stem cell maintenance. In front of recent and numerous evidences highlighting mTOR upregulation in GBM, all the strategies developed to inhibit this pathway have been substantially unsuccessful. Our study focused on mTOR complex 2 (mTORC2) to understand its involvement in GBM cell growth, proliferation, migration and invasiveness. We utilized an in vitro model, characterized by various genetic alterations (i.e., GL15, U257, U87MG and U118MG cell lines) in order to achieve the clonal heterogeneity observed in vivo . Additionally, being the U87MG cell line endowed with glioblastoma stem cells (GSCs), we also investigated the role of the PTEN/PI3K/AKT/mTOR pathway in this specific cell population, which is responsible for GBM relapse. We provide further insights that explain the reasons for the failure of numerous clinical trials conducted to date targeting PI3K or mTOR complex 1 (mTORC1) with rapamycin and its analogs. Additionally, we show that mTORC2 might represent a potential clinically valuable target for GBM treatment, as proliferation, migration and GSC maintenance appear to be mTORC2-dependent. In this context, we demonstrate that the novel ATP-competitive mTOR inhibitor PP242 effectively targets both mTORC1 and mTORC2 activation and counteracts cell proliferation via the induction of high autophagy levels, besides reducing cell migration, invasiveness and stemness properties.

It has long been proven that neurogenesis continues in the adult brains of mammals in the dentatus gyrus of the hippocampus due to the presence of neural stem cells. Although a large number of studies have been carried out to highlight the localization of vitamin D receptor in hippocampus, the expression of vitamin D receptor in neurogenic dentatus gyrus of hippocampus in Parkinson's disease (PD) and the molecular mechanisms triggered by vitamin D underlying the production of differentiated neurons from embryonic cells remain unknown. Thus, we performed a preclinical in vivo study by inducing PD in mice with MPTP and showed a reduction of glial fibrillary acidic protein ( GFAP) and vitamin D receptor in the dentatus gyrus of hippocampus. Then, we performed an in vitro study by inducing embryonic hippocampal cell differentiation with vitamin D. Interestingly, vitamin D stimulates the expression of its receptor. Vitamin D receptor is a transcription factor that probably is responsible for the upregulation of microtubule associated protein 2 and neurofilament heavy polypeptide genes. The latter increases heavy neurofilament protein expression, essential for neurofilament growth. Notably N-cadherin, implicated in activity for dendritic outgrowth, is upregulated by vitamin D.

Depending on the species, microglial cells represent 5-20% of glial cells in the adult brain. As the innate immune effector of the brain, microglia are involved in several functions: regulation of inflammation, synaptic connectivity, programmed cell death, wiring and circuitry formation, phagocytosis of cell debris, and synaptic pruning and sculpting of postnatal neural circuits. Moreover, microglia contribute to some neurodevelopmental disorders such as Nasu-Hakola disease (NHD), and to aged-associated neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and others. There is evidence that human and rodent microglia may become senescent. This event determines alterations in the microglia activation status, associated with a chronic inflammation phenotype and with the loss of neuroprotective functions that lead to a greater susceptibility to the neurodegenerative diseases of aging. In the central nervous system (CNS), Triggering Receptor Expressed on Myeloid Cells 2-DNAX activation protein 12 (TREM2-DAP12) is a signaling complex expressed exclusively in microglia. As a microglial surface receptor, TREM2 interacts with DAP12 to initiate signal transduction pathways that promote microglial cell activation, phagocytosis, and microglial cell survival. Defective TREM2-DAP12 functions play a central role in the pathogenesis of several diseases. The CX3CL1 (fractalkine)-CX3CR1 signaling represents the most important communication channel between neurons and microglia. The expression of CX3CL1 in neurons and of its receptor CX3CR1 in microglia determines a specific interaction, playing fundamental roles in the regulation of the maturation and function of these cells. Here, we review the role of the TREM2-DAP12 and CX3CL1-CX3CR1 axes in aged microglia and the involvement of these pathways in physiological CNS aging and in age-associated neurodegenerative diseases., Competing Interests: The authors declare no conflict of interest.

Cancer of the oral cavity is known to have a diverse aetiology that includes infectious agents. Human papilloma virus has been found to be associated with several types of human cancer, inclusive of cervical, vulvar, vaginal, penile, anal, and cancer of tonsil. The aim of this manuscript is to investigate the presence of human papilloma virus in tonsillar microbiota of an Afghan population group. A sample of the tonsillar microbiota was collected by oral swab paper stick from 80 healthy donors. The sample was investigated for the presence of high-risk human papillomavirus types 16, 18, 31 and 45 by real time PCR. Eight samples produced some positive endpoint signals for human papillomaviruses. The human papillomavirus 31 was the unique papillomavirus detected; its calculated prevalence rate was 0.10 (C.I. 0.05-0.19). However, the viral load was always very low, in the order of 10-3 viral genomes per cell. The high prevalence of high-risk human papillomavirus in healthy population suggest a need for further investigation on virus spreading and supports the development of vaccination strategies.

In addition to tobacco and alcohol consumption, the two main risk factors for oral squamous cell carcinoma (OSCC), recent studies have revealed infections with human papilloma virus (HPV) as an additional risk factor for OSCC development. In the field of head and neck malignancies, the prevalence of HPV infections in oropharyngeal cancer (OC) ranges in different studies up to 84%. While HPV infection is discussed as an independent risk factor in this region, its distinguished role in carcinogenesis of tumours localized to the oral cavity remains uncertain. A systematic literature search was performed using PubMed, Cochrane library, Science Direct, and the Internet search, with language restricted to English. The search included published studies which dealt with detection methods of HPV-related oral and oropharyngeal cancers and biomolecular studies, particularly regarding the compromising of p53 p16 and e-cadherin’s. P53 Tumour suppressor protein p53 has several functions that are related to maintaining genomic stability and inhibiting cell proliferation in response to DNA damage. For preventing neoplasia to occur, the most important of these functions are cessation of cell growth and induction of either apoptosis or senescence. P16 is a cellular protein involved in cell cycle regulation. It is a cyclin-dependent kinase 4 (CDK4) inhibitor, and is integral to Rb mediated regulation of G1-S phase of the cell cycle. P16 is expressed at a very low level in normal cell as Rb inhibits transcription of p16. Various detection methods ranging from immunohistochemistry (IHC) to molecular techniques have been used to determine the HPV status of HNSCC. E-cadherin, a 120 kDa Type I classical cadherin, is expressed primarily on epithelial cells. It is found on the surface of keratinocytesand Langerhans cells (LC) and E-cadherin mediated adhesion between these cell types is required for LC retention in the epidermis. It is also an important tumour suppressor protein: its loss or inactivation is associated with epithelial-to-mesenchymal transition (EMT), a process involving dedifferentiation, infiltration and metastasis of tumours. Oral carcinogenesis is a multi-factorial process involving socioeconomic, environmental and microbial factors leading to multistep changes. Smoking and tobacco exposure seems to modify the survival and recurrence of HPV positive tumours and should be considered in future trials for risk stratification of HPV positive patients. HPV associated oropharynx cancer represents a distinct clinical and biologic entity with many unresolved issues that will be investigated in future translational, clinical research. We need to further explore and understand why the disease occurs predominantly in males, and whether the natural history of oral HPV infection differences in men and women.

The aim of this paper is to describe the efficacy of Human Papilloma Virus (HPV) vaccines for preventing oral cancer. A systematic review of the literature was conducted to describe the state of the art about HPV vaccines for preventing oral cancer. The aspects of prevention and control of infection by administering vaccines and the diffusion of sexual education campaigns are discussed also. In recent years there has been a growing interest in HPV in dentistry, suggesting a role of such a family of viruses in the development of oral cancers as well as of the uterine cervix. Even if the mass media have increasingly faced the problem, causing frequent alarming among patients, the dentist therefore needs a complete and up-to-date knowledge of this infectious condition that is one of the most common causes of sexually transmitted mucous membrane infections (eg genital, anal and oral). Recent studies about HPV infection are a basic requirement in order to promote the HPV vaccinations and patient’s health.

Nowadays, an increasing number of dentists are using intraoral scanners (IOS) in their daily practice as an alternative to conventional impression taking. One of the main concerns is related to the capability of scanning the subgingival anatomy of the die, usually very challenging due to the limited operative field and the presence of oral fluids. The radiosurgery assisted gingival displacement technique (RAGD) may enhance the intraoral optical scanning of the finish line and neighbor tooth anatomy. The contour of the interim prosthesis is used to drive the tip of radiosurgery electrode along the tooth surface and open selectively the gingival crevice with a prosthetically-driven and minimally invasive approach. The clinical implication of this technique is related to increasing the efficiency and accuracy of the digital impression technique in the critical zone of the prosthetic shoulder.

Muscles of sarcopenic people show hypotrophic myofibers and infiltration with adipose and, at later stages, fibrotic tissue. The origin of infiltrating adipocytes resides in fibro-adipogenic precursors and nonmyogenic mesenchymal progenitor cells, and in satellite cells, the adult stem cells of skeletal muscles. Myoblasts and brown adipocytes share a common Myf5 + progenitor cell: the cell fate depends on levels of bone morphogenetic protein 7 (BMP-7), a TGF-β family member. S100B, a Ca 2+ -binding protein of the EF-hand type, is expressed at relatively high levels in myoblasts from sarcopenic humans and exerts anti-myogenic effects via NF-κB-dependent inhibition of MyoD, a myogenic transcription factor acting upstream of the essential myogenic factor, myogenin. Adipogenesis requires high levels of ROS, and myoblasts of sarcopenic subjects show elevated ROS levels. Here we show that: (1) ROS overproduction in myoblasts results in upregulation of S100B levels via NF-κB activation; and (2) ROS/NF-κB-induced accumulation of S100B causes myoblast transition into brown adipocytes. S100B activates an NF-κB/Ying Yang 1 axis that negatively regulates the promyogenic and anti-adipogenic miR-133 with resultant accumulation of the brown adipogenic transcription regulator, PRDM-16. S100B also upregulates BMP-7 via NF-κB/Ying Yang 1 with resultant BMP-7 autocrine activity. Interestingly, myoblasts from sarcopenic humans show features of brown adipocytes. We also show that S100B levels and NF-κB activity are elevated in brown adipocytes obtained by culturing myoblasts in adipocyte differentiation medium and that S100B knockdown or NF-κB inhibition in myoblast-derived brown adipocytes reconverts them into fusion-competent myoblasts. At last, interstitial cells and, unexpectedly, a subpopulation of myofibers in muscles of geriatric but not young mice co-express S100B and the brown adipocyte marker, uncoupling protein-1. These results suggest that S100B is an important intracellular molecular signal regulating Myf5 + progenitor cell differentiation into fusion-competent myoblasts or brown adipocytes depending on its levels.

Objectives: The purpose of this paper is to investigate the effectiveness and to describe a clinical protocol with digital CAD CAM chairside workflow for the rehabilitation of severely compromised and worn dentitions., Methods: This article reports 4 consecutive cases, where a clinical digital chairside workflow is used for the rehabilitation of severely compromised and worn dentitions. Advantages and limitations of this method compared with the traditional prosthetic protocol are also described and discussed., Results: With all four patients treated with this protocol, we obtained a good aesthetic and functional result, improvement in chewing function, loss of cold sensitivity, better preservation of most of the left hard tissue and a good level of satisfaction. In a two-year follow-up, all patients also maintained the condition obtained with prosthetic chairside rehabilitation, resulting in almost 100% cumulative survival rate., Conclusion: Within the limitations of this study, we can assert that the aforementioned restorative treatment with digital CAD/CAM chairside workflow represents a valid alternative to rehabilitate this kind of patients, because it is a safe, predictable and personalized procedure but also it seems easier, faster and cheaper than traditional protocols.

In vertebrates, during an early wave of hematopoiesis in the yolk sac between embryonic day E7.0 and E9.0, cells of mesodermal leaflet addressed to macrophage lineage enter in developing central nervous system (CNS) and originate the developing native microglial cells. Depending on the species, microglial cells represent 5-20% of glial cells resident in adult brain. Here, we briefly discuss some canonical functions of the microglia, i.e., cytokine secretion and functional transition from M1 to M2 phenotype. In addition, we review studies on the non-canonical functions of microglia such as regulation of phagocytosis, synaptic pruning, and sculpting postnatal neural circuits. In this latter context the contribution of microglia to some neurodevelopmental disorders is now well established. Nasu-Hakola (NHD) disease is considered a primary microgliopathy with alterations of the DNAX activation protein 12 (DAP12)-Triggering receptor expressed on myeloid cells 2 (TREM-2) signaling and removal of macromolecules and apoptotic cells followed by secondary microglia activation. In Rett syndrome Mecp2 -/- microglia shows a substantial impairment of phagocytic ability, although the role of microglia is not yet clear. In a mouse model of Tourette syndrome (TS), microglia abnormalities have also been described, and deficient microglia-mediated neuroprotection is obvious. Here we review the role of microglial cells in neurodevelopmental disorders without inflammation and on the complex role of microglia in developing CNS.

Lysosomal alpha-mannosidase with acidic pH optimum is ubiquitous in human tissues where is expressed in two major forms, A and B that are the product of a single gene located on chromosome 19. Mutations in the gene encoding for alpha-mannosidase cause alpha- mannosidosis, an autosomal recessive disease, resulting in the accumulation of unprocessed mannose containing oligosaccharide material. This rare disease has an estimated incidence of 1/500.0.00 live births and clinically is divided into three subgroups. Today the most promising therapy for this disease is the enzyme replacement therapy. To develop this strategy a mouse model for alpha-mannosidosis has been generated and a recombinant human alpha-mannosidase has been produced from Chinese-hamster ovary cells. Interestingly it has been shown that the recombinant enzyme, used in high dose, can cross the blood brain barrier. This recombinant enzyme has been tested in the first randomized study investigating the efficacy of enzyme replacement therapy in patients with alpha-mannosidosis. This review contains the scientific progresses on lysosomal alpha-mannosidase from the cloning to the beginning of the therapy.

Neutral sphingomyelinase is known to be implicated in growth arrest, differentiation, proliferation, and apoptosis. Although previous studies have reported the involvement of neutral sphingomyelinase in hippocampus physiopathology, its behavior in the hippocampus during Parkinson's disease remains undetected. In this study, we show an upregulation of inducible nitric oxide synthase and a downregulation of neutral sphingomyelinase in the hippocampus of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced mouse model of Parkinson's disease. Moreover, the stimulation of neutral sphingomyelinase activity with vitamin 1,25-dihydroxyvitamin D3 reduces specifically saturated fatty acid sphingomyelin by making sphingomyelin a less rigid molecule that might influence neurite plasticity. The possible biological relevance of the increase of neutral sphingomyelinase in Parkinson's disease is discussed.

Glioblastoma (GBM) is the most malignant and aggressive among primary brain tumors, characterized by very low life expectancy. In vivo, glioma and glioblastoma in particular contain large numbers of immune cells (myeloid cells) such as microglia and tumour-infiltrating macrophages (or glioma associated macrophages). These glioma-infiltrating myeloid cells comprise up to 30% of total tumor mass and have been suggested to play several roles in glioma progression including proliferation, survival, motility and immunosuppression. Although tumor microglia and macrophages can acquire proinflammatory (M1) phenotype being capable of releasing proinflammatory cytokines, phagocytosing and presenting antigens, their effector immune function in gliomas appears to be suppressed by the acquisition of an anti-inflammatory (M2) phenotype. In the present work we review the microglia-glioma interactions to highlight the close relationship between the two cell types and the factors that can influence their properties (chemokines, cytokines, S100B protein). A future therapeutic possibility might be to simultaneously targeting, for example with nanomedicine, glioma cells and microglia to push the microglia towards an antitumor phenotype (M1) and/or prevent glioma cells from "conditioning" by microglia.

Aim: The objective of this study was to compare different approaches temporary restoration in an immediate implant placement. To determine the respective influence of each parameter, two treatment groups were formed; a strict and standardized study protocol was applied to minimize the influence of bias and confounding factors. The Pink Esthetic Score (PES) - the esthetic out-come of soft tissue appearance was evaluated., Material and Methods: Sixteen patients with a single failing tooth in the maxilla and a natural contralateral site were randomly distributed into two groups. Treatment variations affected the provisional restorative in detail, group 1 with immediate implant placement and immediate temporary restoration with the simulation of the first three mm of the root and the seal of the socket, group 2 with immediate implant placement and immediate temporary restoration without the seal of the socket. All patients received the final prosthetic restoration 10-12 weeks after implant placement. Standardized photographs were taken eight months after tooth extraction. Five competent observers analyzed the esthetic outcome according to the PES., Results: The overall scores of the four treatment groups revealed PES values of 8.47 (SD 2.08, group 1), 6.62 (SD 3.24, group 2). The differences between groups 1 and 2 and were statistically significant (P=0.015 and P=0.047). The single parameter analysis displayed a certain range of fluctuation and heterogeneity., Conclusions: Immediate implant placement and restoration appear to be a suitable alternative to early implant placement if an experienced surgeon is entrusted with the implantation procedure.

Purpose: The aim of the present study is to demonstrate the efficacy of HyBeNX® to decontaminate the implant surface, both in the case mucositis and severe peri-implantitis and to allow future bone regeneration., Materials and Methods: We describe three case reports of peri-implantitis successfully treated with HyBeNX®. In our study, we have used microbiological tests to demonstrate the efficacy of HyBeNX® in decreasing bacterial load., Results: The microbiological results of the clinical cases described show that there was a reduction in the total bacterial count after treatment., Conclusions: The ability of HyBeNX® to dry the surface and remove biofilm may explain the efficacy of the decontamination and subsequent clinical improvements in all three cases.

Purpose: The aim of this article is to make a comparative assessment between the modification of the soft-tissue profile, around the healing cap screws (HCSs), following both the traditional flapless surgery (TFS) and a new modified flapless surgery, named Modified Connective Tissue Punch (MCTP) technique., Materials and Methods: 8 patients (3M and 5F) (mean age 54.25±11.247 years) were enrolled in this study. Sixteen two-piece implants were placed on upper jaws, 2 for each patient, 8 with TFS and 8 with MCTP technique. In each patient the implants were placed in edentulous areas, of 2 or 3 adjacent teeth long. MCTP technique was performed on the front implant site (FIS) while the TFS was performed on the rear implant site (RIS). All implants were inserted and covered with healing cap screws (HCSs). Alginate impressions were carried out at the moment of the surgery, at 1 month and 4 months post-operative. Plaster models were poured and subsequently digitally scanned, in order to measure the distance between the gingival outline and the free margin of the HCS. The recorded values were analyzed with the ANOVA test., Results: The use of MTCP technique, in comparison to TFS, showed a significative better outcome, in terms of vertical increments, of gingiva, on the VS toward the HCSs, during the entire observation period (p = 0.000 for all)., Conclusion: The Authors recommend the use of MCTP technique for a better vestibular soft tissue outcome in flapless implant surgery.

Background: The aim of this paper was to evaluate the efficacy and safety of topical cyclosporine applied as mouthwash in the treatment of burning mouth syndrome (BMS)., Methods: This was a prospective and pilot study conducted by the Department of Dermatology of the University of Rome Tor Vergata. Patients were treated with cyclosporine topically applied as mouthwash for 4 weeks. Clinical improvement was assessed using a 5 grade clinical evaluation scale and a visual analogue scale from 0 to 10 was also used to evaluate the burning symptoms., Results: Fifteen patients between 22-85 years (61.1±19.3), 11 female and 4 male, with a mean duration of BMS of 12.5 months, completed the study. Five out of 15 patients presented a marked improvement, 6 patients showed a moderate response, 3 patients had a slight improvement and 1 patient did not show any change. The VAS showed a reduction from 8.7 to 3.5. Adverse events were not reported., Conclusions: Cyclosporine mouthwash appeared to be safe and beneficial for reducing the burning sensation in patients with BMS representing an alternative therapy in this condition.

The importance of HPV in world healthy is high, in fact high-risk HPV types contribute significantly to viral associated neoplasms. In this article we will analyze vary expression of HPV in oral cavity both benign and malignant, their prevalence and the importance in early diagnosis and prevention. The classical oral lesions associated with human papillomavirus are squamous cell papilloma, condyloma acuminatum, verruca vulgaris and focal epithelial hyperplasia. Overall, HPV types 2, 4, 6, 11, 13 and 32 have been associated with benign oral lesions while HPV types 16 and 18 have been associated with malignant lesions, especially in cancers of the tonsils and elsewhere in the oropharynx. Transmission of the virus can occur with direct contact, genital contact, anal and oral sex; latest studies suggest a salivary transmission and from mother to child during delivery. The number of lifetime sexual partners is an important risk factor for the development of HPV-positive head-neck cancer. Oral/oropharyngeal cancer etiologically associated with HPV having an increased survival and a better prognostic (85%-90% to five years). There is no cure for the virus. There are two commercially available prophylactic vaccines against HPV today: the bivalent (16 and 18) Cervarix® and the tetravalent (6, 11, 16 and 18) Gardasil® and new vaccine Gardasil 9 (6, 11, 16, 18, 31, 33, 45, 52, 58) was approved in the United States. To be effective, such vaccination should start before "sexual puberty". The vaccine could be an important preventive strategy, in fact the scientific community is in agreement on hypothesis that blocking the contagion it may also limit the distance complications as the oropharyngeal cancer.

Purpose: This study describes the ability to perform a technique for bone regeneration in maxillary posterior deficit (TGSL) without the use of bone grafting materials using a highly minimally invasive protocol., Materials and Methods: Sixty six implants have been inserted in the sinus floor of a total of 39 patients through the transcrestal guided sinus lift technique (TGSL). All patients have been followed for at least three years in function. The drilling protocol was adapted on the basis of bone density of each implant site to achieve a torque between 45 and 55 Ncm. Healing titanium abutments tightened to 35 Ncm have been used. A CAD/CAM metal ceramics final prosthetic restoration has been generated a six months after the tissues healing and the provisional functionalization of the occlusion. Survival rate of implants and prostheses, biological and biomechanical complications, changes in marginal bone levels, and total height of alveolar crest bone before and after surgery have been evaluate and measured by the results obtained in this prospective study. It was also measured the periodontal parameters as well as levels of perception of pain by the patient during the entire recovery period., Results: The result of the data of follow-up was 41.96 (24 to 36) months. Cumulative implant survival was 98.53% at 3 years. There were no biological and mechanical complications and there were no prosthetic failures during the whole period of follow-up. The Marginal Bone Loss (MBL) average during the first year of operation was from 0.33 to 0.36 mm, while the 3-year follow-up, the MBL average was 0.51 to 0.29 mm. The average of residual bone height of alveolar ridge before treatment was 6.7 to 1.6 mm (range 5.1 to 9.2 mm), while the average bone height was gained 6,4 - 1.6 mm (range 3.2 to 8.1 mm). All patients reported lower pain levels and found to have normal periodontal parameters., Conclusions: This study suggests that the use of guided surgery to perform transcrestal maxillary sinus lift to increase the sub-antral crestal height is a minimally invasive technique of success for the short and medium-term of follow-up, thus avoiding the extended treatment time and reducing the morbidity associated with the lifting of the floor of the maxillary sinus with traditional technique using bone grafting materials. Furthermore, this protocol without the use of graft materials does not vary the final outcome that have demonstrated the presence of newly formed bone around implants offering always predictable results, and giving a further reduction in the costs of the procedure rehabilitation.

Objectives: Modern dentistry increasingly tends to use materials aesthetically acceptable and biomimetic. Among these are zirconia and ceramics for several years, a combination that now has becoming synonym of aesthetic; however, what could be the real link between these two materials and especially its nature, remains a controversial topic debated in the literature. The aim of our study was to "underline" the type of bonding that could exist between these materials., Materials and Methods: To investigate the nature of this bond we used a SEM microscopy (Zeiss SUPRA 25). Different bilaminar specimens: "white" zirconia Zircodent® and ceramic "Noritake®", after being tested with loading test in bending (three-point-bending) and FEM analysis, were analyzed by SEM. Fragments' analysis in closeness of the fracture's point has allowed us to be able to "see" if at large magnifications between these two materials, and without the use of linear, could exist a lasting bond and the possible type of failure that could incur., Results: From our analysis of the specimens' fragments analyzed after test Equipment, it is difficult to highlight a clear margin and no-adhesion zones between the two materials, although the analysis involving fragments adjacent to the fracture that has taken place at the time of Mechanical test Equipment., Conclusions: According to our analysis and with all the clarification of the case, we can assume that you can obtain a long and lasting bond between the zirconia and ceramics. Agree to the data present in the literature, we can say that the type of bond varies according to the type of specimens and of course also the type of failure. In samples where the superstructure envelops the ceramic framework Zirconium we are in the presence of a cohesive failure, otherwise in a presence of adhesive failure.

Objectives: Bone regeneration is often needed prior to dental implant treatment due to the lack of adequate quantity and quality after infectious diseases. The greatest regenerative power was obtained with autologous tissue, primarily the bone alive, taken from the same site or adjacent sites, up to the use centrifugation of blood with the selection of the parts with the greatest potential regenerative. In fact, various techniques and technologies were chronologically successive to cope with an ever better preparation of these concentrates of blood. Our aim is to review these advances and discuss the ways in which platelet concentrates may provide such unexpected beneficial therapeutic effects., Methods: The research has been carried out in the MEDLINE and Cochrane Central Register of Controlled Trials database by choosing keywords as "platelet rich plasma", "platelet rich fibrin", "platelet growth factors", and "bone regeneration" and "dentistry"., Results: Autologous platelet rich plasma is a safe and low cost procedure to deliver growth factors for bone and soft tissue healing., Conclusion: The great heterogeneity of clinical outcomes can be explained by the different PRP products with qualitative and quantitative difference among substance.

Systemic sclerosis (SSc) is a connective tissue disease, characterized by cutaneous and multi-organ fibrosis, and vascular abnormalities. Skin thickening is a characteristic feature of SSc and resembles myxedematous skin. Our aim was to correlate the degree of skin involvement in SSc patients with serum TSH levels, since TSH receptors are widely expressed in human tissues, including the skin. In this cross-sectional study, we enrolled 70 SSc patients, all females with a mean age of 47 ± 11 year. Thirty-five age- and sex-matched HT patients were recruited, as controls. Subjects under L-thyroxine therapy and/or with positive anti-TSH receptor antibodies were excluded. In all subjects, we measured serum TSH, FT4, and free tri-iodothyronine (FT3) levels. Skin thickness was evaluated using the modified Rodnan total skin score (mRSS). mRSS averaged 14 ± 9 for SSc and 4 ± 6 for HT patients. TSH levels positively correlated with skin scores in both SSc and HT patients groups. In SSc patients, FT3 and FT4 showed an inverse correlation with mRSS, while in HT only FT4 levels showed this inverse significance. When divided by cutaneous extent, SSc patients with diffuse disease form had higher TSH serum levels compared to those with the limited form; additionally, the correlations between TSH, FT4, and mRSS reached statistical significance. Our preliminary data clearly indicate that serum TSH is higher in SSc patients with more severe skin disease, and significantly correlate with the mRSS. Therefore, TSH could play a role in the development of cutaneous changes in SSc patients.

Trauma of anterior teeth is quite a common occurrence in both children and adults. Various degrees of trauma leading to fracture may affect teeth in different ways depending on the age of the patient and extent of fracture and other factors that will be discussed. Guidelines have been given as to how each of these situations should be treated. In the past, often more aggressive restorations were performed to restore fractured teeth. However improved and more efficient adhesion may affect the type of treatment we decide to carry out, leading to more conservative therapies through an increased preservation of tooth structures., Competing Interests: The authors deny any conflict of interests. They affirm that they have no financial affiliation (e.g., employment, direct payment, stock holdings, retainers, consultantships, patent licensing arrangements, or honoraria) or involvement with any commercial organization with direct financial interest in the subject or materials discussed in this manuscript, nor have any such arrangements existed in the past three years. Any other potential conflict of interests is disclosed.

Aim: The aim of the study was to evaluate the short-term and long-term toxicity caused by radiation treatment in the head and neck with the technique of intensity-modulated radiotherapy (IMRT)., Methods: We selected 20 patients, 18 men and 2 women aged between 21 and 71 years, undergoing radiation therapy (IMRT) in head and neck. Patients were visited during radiotherapy and followed for six months after the end of the therapy. We assessed the presence of: mucositis, xerostomia, dysgeusia, dysphagia, pain, trismus and, in the case of late-onset complications, radiation cavities., Results: Acute toxicity: in 20 patients, 18 reported mucositis, 19 xerostomia, 17, dysgeusia, 15 dysphagia, 18 had pain and 3 patients had trismus. Tardive toxicity: in 14 patients, 5 reported mucositis, 11 xerostomia, 6 dysgeusia, 2 dysphagia, 3 had pain, 4 trismus and in 4 patients were found radiation cavities., Conclusion: Acute complications with higher prevalence were xerostomia (19 of 20 patients), dysgeusia of 2nd grade (11 patients of 20), mucositis of 1st grade and pain of 1st grade (10 patients of 20). Among the late complications it was noted a maintenance of the high prevalence of xerostomia (11 patients of 14) and an increase in prevalence of trismus (4 patients of 14) against a reduction of all other complications. The presence of radiation cavities in 4 patients of 14 was also recorded.

Purpose: The aim of this paper was to describe the CEREC 3 chairside system, providing the clinicians a detailed analysis of the whole digital workflow. Benefits and limitations of this technology compared with the conventional prosthetic work-flow were also highlighted and discussed., Materials and Methods: Clinical procedures (tooth preparation, impression taking, adhesive luting), operational components and their capabilities as well as restorative materials used with CEREC 3 chairside system were reported., Results: The CEREC system has shown many positive aspects that make easier, faster and less expensive the prosthetic workflow. The operator-dependent errors are minimized compared to the conventional prosthetic protocol. Furthermore, a better acceptance level for the impression procedure has shown by the patients. The only drawback could be the subgingival placement of the margins compared with the supra/juxta gingival margins, since more time was required for the impression taking as well as the adhesive luting phase. The biocopy project seemed to be the best tool to obtain functionalized surfaces and keep unchanged gnathological data. Material selection was related to type of restoration., Conclusions: The evidence of our clinical practice suggests that CEREC 3 chairside system allows to produce highly aesthetic and reliable restorations in a single visit, while minimizing costs and patient discomfort during prosthetic treatment. However improvements in materials and technologies are needed in order to overcome the actual drawbacks.

The extraction of third molars (wisdom teeth) is one of the main surgical procedures performed in dentistry. The aim of this study was to describe the characteristics of patients undergoing the procedure in the SGC Fatebenefratelli Hospital, a large hospital in Rome (Italy), where about 20% of all third molar extractions in the Lazio Region are performed. Hospital discharge forms were analysed for patients discharged in the years 2010 and 2011 with a Diagnosis Related Group (DRG) code 169, used for the procedure. Study results indicate that the extraction of third molars is a relevant public health issue considering its frequency and associated yearly costs at the national level. The appropriateness of third molar extraction, especially when performed prophylactically in young persons, should be further explored.

We proposed that group IIA secretory phospholipase A(2) (GIIA) participates in neuritogenesis based on our observations that the enzyme migrates to growth cones and neurite tips when PC12 cells are induced to differentiate by nerve growth factor (NGF) (Ferrini et al., Neurochem Res 35:2168-2174, 2010). The involvement of other secretory PLA(2) isoforms in neuronal development has been suggested by others but through different mechanisms. In the present study, we compared the subcellular distribution of GIIA and group X sPLA(2) (GX) after stimulation of PC12 cells with NGF. We found that GIIA, but not GX, localized at the neuritic tips after treatment with NGF, as demonstrated by immunofluorescence analysis. We also found that NGF stimulated the expression and the activity of GIIA. In addition, NGF induced the expressed myc-tagged GIIA protein to migrate to neurite tips in its active form. We propose that GIIA expression, activity, and subcellular localization is regulated by NGF and that the enzyme may participate in neuritogenesis through intracellular mechanisms, most likely by facilitating the remodelling of glycerophospholipid molecular species by deacylation-reacylation reactions necessary for the incorporation of polyunsaturated fatty acids.

Objective: Although waste is traditionally assessed as a pollutant which needs to be reduced or lessened, its management is certainly necessary. Nowadays, biological fuel cells, through the direct conversion of organic matter to electricity using biocatalysts, represent a technology able to produce sustainable energy by means of waste treatment. This study aims to propose a mean to generate energy from blood and saliva, that are common risk-infectious medical waste., Materials and Methods: Material employed (purchased by Sigma-Aldrich) were: Glucose oxidase (GOx), Nafion perfluorinated resin solution at 5% in a mixture of lower aliphatic alcohols and water, Polyethylene oxide. Stock solutions of D (+) glucose were prepared in a 0.1 M phosphate buffer solution and stored at 4 °C for at least 24 h before use. Carbon cloth electrode ELAT HT 140 E-W with a platinum loading of 5 gm-2 was purchased by E-Tek. Electrospun Nafion fibers were obtained as follows. Scanning electron microscopy was used to characterize the electrode morphologies., Results: In order to develop an effective immobilization strategy of GOx on the electrode surface, Nafion fibers (a fully fluorinated ion conducting polymer used as a membrane material in enzymatic fuel cells - EFC) were selected as immobilizing polymer matrix. In this work, exploiting the nafion fibers capability of being able to cathalize Gox activity, we have tried to produce an enzymatic fuel cell which could produce energy from the blood and the saliva within medical-dental waste., Conclusions: Medical waste refers to all those materials produced by the interaction among doctor and patient, such as blood and saliva. During our research we will try to complete an EFC prototype able to produce energy from blood and saliva inside the risk-infectious medical waste in order to contribute to the energy requirements of a consulting room.

The medium-long term success of osseointegrated dental implants is evaluated on the basis of the degree of osseointegration over time, assessed by radiographic or instrumental analysis (ISQ). Over the years, the question has always been which surgical technique can provide a better performance in the medium-long term and, thanks to literature studies, it has been evidenced that there are no differences between "one stage" and "two stage" interventions. The purpose of this study is to evaluate clinical and radiographic parameters, referring to interventions for the insertion of dental implants characterized by a new kind of implant surface (Synthegra® GEASS, Udine). The prospective study, not randomized and controlled, referred to the insertion of 18 implants on 9 patients with mono or bilateral edentulism, with measurements at 1, 3, 6 and 12 months and an overall follow-up at 3 years, in order to evaluate the different degree of crestal bone resorption using the submerged and transmucosal surgical technique. The results of our study show that there are no differences in the resorption of the two surgical techniques, with an average bone resorption of 2,05±0,16 mm, comparable with values reported in literature.

Objective: Over the last several years, the Finite Element Analysis (FEM) has been widely recognized as a reference method in different fields of study, to simulate the distribution of mechanical stress, in order to evaluate the relative distribution of loads of different nature. The aim of this study is to investigate through the FEM analysis the stress distribution in fixed prostheses that have a core in Zirconia and a ceramic veneer supported by implants., Materials and Methods: In this work we investigated the mechanical flexural strength of a ceramic material (Noritake(®)) and a of zirconium framework (Zircodent(®)) and the effects of the manufacturing processes of the material commonly performed during the production of fixed prostheses with CAD/CAM technology. Specifically three point bending mechanical tests were performed (three-point-bending) (1-3), using a machine from Test Equipment Instron 5566(®), on two structures in zirconium framework-ceramic (structures supported by two implant abutments with pontic elements 1 and 2). A further in-depth analysis on the mechanical behavior in flexure of the specimens was conducted carrying out FEM studies in order to compare analog and digital data., Results: The analysis of the data obtained showed that the stresses are distributed in a different way according to the intrinsic elasticity of the structure. The analysis of FPD with four elements, the stresses are mainly concentrated on the surface of the load, while, in the FPD of three elements, much more rigid, the stresses are concentrated near the inner margins of the abutments. The concentration of many stresses in this point could be correlated to chipping (4) that is found in the outer edges of the structure, as a direct result of the ceramic brittleness which opposes the resilience of the structure subjected to bending., Conclusions: The analysis of the UY linear displacement confirms previous data, showing, in a numerical way, that the presence of the ceramic is related to the lowering of the structure. So, the reference values are those of the linear lowering obtained in the Mechanical Test and in our FEM analysis. zirconium framework with four elements 4,227 10(-2)mm.zirconium framework with ceramic structure with four elements 2,266 10(-2) mm.That suggests that the presence of ceramics halves the flexion capabilities of the prosthetic materials.

Objective: Atomic force microscope (AFM) is a technology that allows analysis of the nanoscale morphology of bacteria within biofilm and provides details that may be better useful for understanding the role of bacterial interactions in the periodontal disease., Material and Methods: Five patients with periodontal ≥5 mm pockets diagnosed as generalized periodontitis and five patients with slight gingivitis were selected for the investigation. Bacteria biofilms were collected and morphologically investigated by AFM application., Results: The investigation revealed how periodontitis bacteria are characterized by specific morphologic features of the cell wall. The major representative species of bacteria causing periodontal diseases have been reproduced by a three-dimensional reconstruction showing the bacteria surface details., Conclusions: The presence of complex glycocalyx structures, bacteriophage-like vesicles, spirochetes (classic and cystic morphology) and bacterial co-aggregation has been identified by the AFM analysis. The results suggest that AFM is a reliable technique for studying bacterial morphology and for examining microbial interactions in dental plaque.

The Ca(2+)-binding protein of the EF-hand type, S100B, exerts both intracellular and extracellular regulatory activities. As an intracellular regulator, S100B is involved in the regulation of energy metabolism, transcription, protein phosphorylation, cell proliferation, survival, differentiation and motility, and Ca(2+) homeostasis, by interacting with a wide array of proteins (i.e., enzymes, enzyme substrates, cytoskeletal subunits, scaffold/adaptor proteins, transcription factors, ubiquitin E3 ligases, ion channels) in a restricted number of cell types. As an extracellular signal, S100B engages the pattern recognition receptor, receptor for advanced glycation end-products (RAGE), on immune cells as well as on neuronal, astrocytic and microglial cells, vascular smooth muscle cells, skeletal myoblasts and cardiomyocytes. However, RAGE may not be the sole receptor activated by S100B, the protein being able to enhance bFGF-FGFR1 signaling by interacting with FGFR1-bound bFGF in particular cell types. Moreover, extracellular effects of S100B vary depending on its local concentration. Increasing evidence suggests that at the concentration found in extracellular fluids in normal physiological conditions and locally upon acute tissue injury, which is up to a few nM levels, S100B exerts trophic effects in the central and peripheral nervous system and in skeletal muscle tissue thus participating in tissue homeostasis. The present commentary summarizes results implicating intracellular and extracellular S100B in tissue development, repair and regeneration.

OBJECTIVE.: Podoplanin is a mucin-like glycoprotein that is important in lymphangiogenesis but not in blood vessel formation. The aim of this preliminary study is to determine the role of podoplanin in the development and progression of head and neck cancer. MATERIAL AND METHODS.: Podoplanin over expression was analyzed in 20 patients with oral cancer, by immunohistochemical analysis. RESULT.: Podoplanin is not expressed in normal oral epithelial cells but was found in some hyperplastic and dysplastic lesions. Podoplanin high expression was found in 9 of 20 patients and was more frequent in cancers with lymph node metastasis, particularly in oral cavity cancers. In our preliminary study, patients who showed high levels of podoplanin had a statistically greater rate of lymph node metastasis (P<0,001); patients with lymph node metastasis and high-level podoplanin showed a shorter disease-specific survival (P = 0,004) than other patients. CONCLUSION.: The results of our preliminary study have provided interesting and encouraging data. We have observed that podoplanin expression increases in the early stages of tumourigenesis and it seems to be associated with a higher risk of head and neck cancer. While in squamous cell carcinoma podoplanin expression diminishes during tumour progression. These data support a role for podoplanin expression in the initiation but not in the progression of cancer. So we can conclude that podoplanin is involved in oral oncogenesis and can be a predictor for lymph node metastasis in asymptomatic patients. Histology and podoplanin analysis can be very useful to predict the risk of development, invasion and metastatic progression of a tumour in patients with oral cancer.

Unlabelled: INTRODUCTION.: Nasopalatine duct cysts (NPDCs) are the most common developmental epithelial non-odontogenic cysts of the maxillae. Their origin, however, is still a source of considerable debate. AIMS.: The aim of this investigation is to describe and discuss the etiology, differential diagnosis, clinic-pathological characteristics as well as to report the relative frequency and distribution of nasopalatine duct cysts in population (NPDCs) with a literature's review on the topic., Methods: The retrospective study was carried out using 36 clinical cases, with histopatological confirmation for NPDC, radiographs and oral photographs. Data included age and gender of the patient, radiographic findings, etiological factors, treatment, and prognosis of NPDC. Few surgical consideration are discussed., Results: The study results report a clear male predilection with a 3:1 ratio. No statistically significant correlation was observed between the size of the lesion and patient's gender. Lesions were usually asymptomatic. All cysts were located in the anterior maxillary midline region. Panoramic X-rays and computed tomography was used to identify the lesion. Surgical treatment was performed under local anesthesia including the dissection and removal of the cyst, adopting a usually palatine approach, with an enveloping flap from 1.4 to 2.4., Conclusions: The etiology of NPDC is unclear and a male predilection was observed. Simple surgical resection is recommended, followed by clinical and radiological control to ensure correct resolution of the case.

Aim: Tooth agenesis is characterised by the congenital absence of one or more teeth. The Pax9 gene has been associated with nonsyndromic forms., Materials and Methods: To investigate the molecular mechanisms, we evaluated specific haplotypes frequency in exon 3 of the Pax9 gene in 26 patients and 21 controls, using an Italian population., Results: Presence of His239His and the Ala240Pro were confirmed in exon 3 of the Pax9 gene. A frequency of 20.2€ of the T allele at position 717 and a C frequency of 33€ of Ala240Pro polymorphism, that reached 40.5€ in the control group, were observed. The 39 C/C-240 C/C or G/Chaplotype which we defined Pax9hapl a had a proportion of 61.9€ in control individuals. The frequency of Pax9hapl a tested in the patients was different from controls, being 81.3€ in normalcy and 18.8€ in oligodontia (p<0.05)., Conclusion: Our observations suggest that Pax9hapl a may have a protective effect against sporadic oligodontia.

OBJECTIVES.: Oral cavity rare diseases include a various group of uncommon morbid conditions. For this reason they are often called "orphan diseases", as they are not interesting for research and the description of their natural history is not easy. The aim of our study is to analyze the prevalence and the distribution of oral cavity rare diseases in order to increase their knowledge and allow a fast therapeutic approach. METHODS AND MATERIAL.: 3144 patients took part to our study, they were choosen according to specific criteria and included in a experimental program; they all were prepared for oral biopsy surgery at Fatebenefratelli Hospital - Tor Vergata University of Rome. Following the results of the histological diagnosis, patients have been grouped. RESULTS.: From 1996 to 2010, we observed 1635 men and 1509 women, average age was 53 years, higher for women (55y.) and lower for men (52y.). CONCLUSIONS.: Nevertheless the low level of accordance and the difficulty in description of natural history of diseases reported in literature, we can conclude that, according to our study the onset of rare diseases shows a percentage of appearing statistically significant.

S100B protein activates IKKβ/NF-κB within myoblasts, thereby inhibiting the expression of MyoD and the MyoD-downstream effectors, myogenin and p21(WAF1), and myoblast differentiation. Herein we show that myoblasts downregulate S100B expression once transferred from proliferation medium to differentiation medium via a p38 MAPK-driven transcriptional mechanism as well as a post-translational, proteasome-dependent mechanism, and that myoblasts that have not been committed to differentiation resume expressing S100B once transferred back to proliferation medium. Likewise, myoblasts downregulate S100B expression once transferred to quiescence medium, and interference with S100B downregulation as obtained by stable overexpression of the protein results in reduced acquisition of quiescence and a faster proliferation upon transfer of the cells from quiescence medium to proliferation medium, compared to controls. These latter effects are dependent on S100B-induced activation of JNK. Moreover, S100B reduces myoblast apoptosis in an MEK-ERK1/2, Akt, JNK, and NF-κB-dependent manner. However, myogenin(+) myoblasts (i.e., myocytes) and myotubes abundantly express S100B likely induced by myogenin. Our results suggest that (1) a timely repression of S100B expression is required for efficient myogenic differentiation; (2) S100B plays an important role in the expansion of the activated (i.e., proliferating) myoblast population; (3) under conditions associated with enhanced expression of S100B, the transition from proliferation to quiescence and from quiescence to proliferation might be altered; and (4) S100B exerts different regulatory effects in myoblasts and myocytes/myotubes/myofibers. This article is part of a Special Issue entitled: 11th European Symposium on Calcium., (2010 Elsevier B.V. All rights reserved.)

Objective: The aim of this phase 2 trial was to evaluate the tolerability and efficacy of combined gemcitabine (G) and epirubicin (E) as second-line treatment for patients with advanced ovarian cancer., Methods: Treatment with G 1000 mg/m2 (days 1 and 8) and E 60 mg/m2 (day 1) every 3 weeks for 3 or, in the absence of progression, 6 courses., Results: Fifty patients with advanced ovarian cancer (31 serous, 2 endometrioid, 10 unclassified adenocarcinoma, and 7 other) and a median age of 60 years (range, 38-74 years) were enrolled after giving their informed consent. Performance status according to the Eastern Cooperative Oncology Group was 0 in 29 patients (58%), 1 in 17 patients (34%), and 2 in 4 patients (8%), and the initial stages according to the International Federation of Gynecology and Obstetrics were I to II in 4 patients (8%), III in 31 patients (62%), and IV in 15 patients (30%). They had previously received a median of 1.5 lines of treatment (range, 1-4). The median platinum-free interval was 5 months (range, 0-12 months): 32 patients had relapse within 6 months and 18 patients had relapse after 6 months. The response rate was 42% (2% complete response and 40% partial response), with a median duration of 7.2 months: the corresponding figures were 37.5% and 5.2 months in the platinum-resistant patients and 50% and 8.8 months in the platinum-sensitive patients. The main grade 3 to 4 hematological toxicity was neutropenia (56% of cases). After a median follow-up of 13.5 months, median progression-free survival was 5 months, and median overall survival was 23.5 months., Conclusions: This E + G combination seems to be active and safe in platinum-resistant/refractory patients.

Aim of the Work: The fragile-X syndrome is the most common cause of inherited mental retardation and it is associated with the FMR1 gene on X chromosome. The origin of anatomic anomalies of maxillo-facial complex is still discussed in literature. The authors describe the syndrome and report a clinical case., Methods: Genetical and clinical aspects and the incidence of caries, periodontal disease and occlusal abrasion are reviewed. Occlusal conditions, particularly openbite and crossbite, are considered., Results: The incidence of fragile-X syndrome is 1: 2000 in males and 1:4000 in females, despite this the syndrome is diagnosed with a lot of difficulties yet, because of extreme variability of the phenomenological aspects. Patients often show severe mental retardation, linked to a peculiar profile of cognitive, behavioural, and emotional dysfunction and to distinctive anatomic features, which become more evident after puberty. Concerning oral characteristics, it doesn't seem to be a significant association between the syndrome and the incidence of caries or periodontal diseases, while an ogival shaped palate is peculiar., Conclusions: Literature review suggests that when male patients with severe mental retardation without well-known cause are visited, the ipothesis of X-fragile syndrome should be considered. Even though the diagnostic hypothesis may arise from the observation of typical somatic features, the diagnosis can be confirmed only by genetical tests.

Recently clinical studies have proved without doubts that in patients affect by neurological diseases, like stroke, parkinsonism syndromes and others neurodegenerative pathologies, there is a very elevated incidence of swallowing disorders even severe. The disease can show up in a full blown way, with clinical evident signs like suffocation or frequent and sudden cough, at the moment in which the patient tries to feed or to drink; or it can appear in a less clear way, through an unable protection of the low airway and with possible pathologies ab ingestis. The first signals are represented by frequent resulting of cough reflex at nutrition or hydratation. Important is to assess the validity of this reflection, monitoring the amount of food reflux in the mouth after swallowing, which then could be perceived like foreign body and be aspired. The main diagnostic tests are the pHmetry in 24h, ultrasound, esophagography, videofluoroscopy, endoscopic examination and scintigraphy. Through the FEES (Fiberoptic Endoscopic Evaluation of Swallowing) we can then identify the time of swallowing deficit. Early diagnosis of Dysphagia Syndrome is important to improve living condition and survival of patients.

S100B, a Ca(2+)-binding protein of the EF-hand type, is expressed in myoblasts, the precursors of skeletal myofibers, and muscle satellite cells (this work). S100B has been shown to participate in the regulation of several intracellular processes including cell cycle progression and differentiation. We investigated regulatory activities of S100B within myoblasts by stable overexpression of S100B and by inhibition of S100B expression. Overexpression of S100B in myoblast cell lines and primary myoblasts resulted in inhibition of myogenic differentiation, evidenced by lack of expression of myogenin and myosin heavy chain (MyHC) and absence of myotube formation. S100B-overexpressing myoblasts showed reduced MyoD expression levels and unchanged Myf5 expression levels, compared with control myoblasts, and transient transfection of S100B-overexpressing myoblasts with MyoD, but not Myf5, restored differentiation and fusion in part. The transcriptional activity of NF-kappaB, a negative regulator of MyoD expression, was enhanced in S100B-overexpressing myoblasts, and blocking NF-kappaB activity resulted in reversal of S100B's inhibitory effects. Yin Yang1, a transcriptional repressor that is induced by NF-kappaB (p65) and mediates NF-kappaB inhibitory effects on several myofibrillary genes, also was upregulated in S100B-overexpressing myoblasts. Conversely, silencing S100B expression in myoblast cell lines by RNA interference resulted in reduced NF-kappaB activity and enhanced MyoD, myogenin and MyHC expression and myotube formation. Thus, intracellular S100B might modulate myoblast differentiation by interfering with MyoD expression in an NF-kappaB-dependent manner., (J. Cell. Physiol. 223: 270-282, 2010. (c) 2009 Wiley-Liss, Inc.)

The Ca(2+)-binding protein of the EF-hand type, S100B, is an intracellular regulator and an extracellular signal. Within cells S100B interacts with several proteins thereby regulating energy metabolism, Ca2+ homeostasis, protein phosphorylation and degradation, and cell locomotion, proliferation and differentiation. Once secreted/released, S100B exerts autocrine and paracrine effects on responsive cells by engaging the receptor for advanced glycation end products. However, recent evidence suggests that S100B might also activate basic fibroblast growth factor receptor 1 via prior binding to basic fibroblast growth factor.

S100B belongs to a multigenic family of Ca(2+)-binding proteins of the EF-hand type and is expressed in high abundance in the brain. S100B interacts with target proteins within cells thereby altering their functions once secreted/released with the multiligand receptor RAGE. As an intracellular regulator, S100B affects protein phosphorylation, energy metabolism, the dynamics of cytoskeleton constituents (and hence, of cell shape and migration), Ca(2+) homeostasis, and cell proliferation and differentiation. As an extracellular signal, at low, physiological concentrations, S100B protects neurons against apoptosis, stimulates neurite outgrowth and astrocyte proliferation, and negatively regulates astrocytic and microglial responses to neurotoxic agents, while at high doses S100B causes neuronal death and exhibits properties of a damage-associated molecular pattern protein. S100B also exerts effects outside the brain; as an intracellular regulator, S100B inhibits the postinfarction hypertrophic response in cardiomyocytes, while as an extracellular signal, (high) S100B causes cardiomyocyte death, activates endothelial cells, and stimulates vascular smooth muscle cell proliferation.