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Introduction: Survivin is a member of the Inhibitor of Apoptosis (IAP) proteins family, broadly expressed in most solid and haematological malignancies, but almost undetectable in normal adult tissues. Regarding Oral Squamous Cell Carcinoma (OSCC), Survivin expression seems to be correlated with aggressive phenotype and unfavorable outcome. In this work, the effectiveness of Survivin detection in saliva samples as diagnostic tool was investigated. Methods: 55 saliva samples from patients with histological diagnosis of OSCC and 30 samples from healthy controls matched for age and gender were collected. All samples from OSCC were collected before therapy. Saliva was analyzed using Assay Designs human Total Survivin TiterZyme® Enzyme Immunometric Assay (EIA) kit for Survivin detection and quantification. Survivin concentration (pg/ml) was studied in relationship to clinical data. Univariate statistical analysis was performed. Results: 35/55 (63.6%) among OSCC patients were found to be positive for surviving expression in saliva vs 12/30 (40%) among health controls; but the mean value was found to be higher in OSCC group (8,69 pg/ml ± 10,15 vs 2.44 pg/ml ± 4.22) reaching statistical significance (p

The aim of this study was to investigate the presence of an inflammatory infiltrate in the peri-implant soft tissue of single-implant crowns supported by either zirconia or titanium abutments in healthy subjects. Serial sections from formalin-fixed, paraffin-embedded blocks from peri-implant mucosa of 25 patients were immunohistochemically analyzed for CD3 and CD20 lymphocyte marker expression. The results showed that levels of T cells (CD3) were higher around zirconia than titanium abutments (p

Oral squamous cell carcinoma (OSCC) is the most common malignancy of oral cavity. Human cancers are characterized by an imbalance of regulatory mechanisms controlling different cellular pathways, including apoptosis. Apoptosis occurs in a wide variety of physiological processes, such as embryonic development, tissue homeostasis or immune defense, and its role is to remove harmful, damaged, or unwanted cells. Defective apoptosis represents an important causative factor in the development/progression of cancer, and the ability of tumor cells to evade apoptosis can play a significant role in their resistance to conventional anticancer treatment. We investigated the expression profile of genes involved in the apoptotic mechanism in 21 paired tissue samples (OSCC and adjacent normal oral mucosa) by cDNA macroarray, in order to identify differentially expressed genes in oral cancer compared to normal tissue. To validate the results obtained by cDNA macroarray, quantitative real-time PCR, Western blot, and immunohistochemical analyses were performed. Results obtained by cDNA macroarray analysis showed different expression levels of CRADD, FADD, ATM, APAF1, and TP63 genes in OSCC compared to normal mucosa. Differential gene expression measurements (tumor vs. normal tissue) performed by real-time PCR showed an overexpression of FADD and a downregulation of ATM. Moreover, Western blot analysis confirmed that both CRADD and APAF-1 were decreased in OSCC compared to normal oral mucosa. As showed by immunohistochemistry, OSCC exhibited increased expression of p63 compared to normal tissue. Interestingly, a statistically significant positive correlation was found between p63 expression and the histological grade.

Oral squamous cell carcinoma (OSCC) is the most common form of head and neck cancer worldwide. In recent decades, the 5-year mortality rate is approximately 50% around the world. As reliable biomarkers of oral cancer are still lacking, it is necessary to identify new target molecules for early diagnosis, effective therapy, and monitoring of the disease. In the present work, we focused on the expression of the enzyme nicotinamide N-methyltransferase (NNMT). We analyzed enzyme activity in 37 paired tumor and non-tumor tissues and found that activity levels are significantly higher in tumor compared with adjacent normal oral mucosa. Interestingly, oral epithelium surrounding tumor of unfavorable cases (N+) seems to display higher activity levels compared with that of favorable ones (N0). Western blot analyses were performed to evaluate protein levels in saliva samples from patients with OSCC and healthy subjects. Preliminary results indicated an up-regulation of salivary NNMT in tumor. This study shows a marked increase in enzyme activity in oral cancer and suggests that adjacent normal tissue of unfavorable cases seems to change toward cancer. Moreover, it is conceivable to hypothesize that NNMT could represent a potential biomarker for early and non-invasive diagnosis of oral cancer.

This paper describes the first outcomes of an activity aiming at validating the H-SAF soil moisture products derived from Metop-ASCAT data. For this purpose, an extensive comparison between SMOS and ASCAT derived soil moisture retrievals has been accomplished by considering the 25 km resolution ASCAT products and the SMOS L2 products. Both Europe and Northern Africa have been considered and data acquired during 2010 have been used. The procedure that has been followed to accomplish the comparison is described together with the first results. The way the ASCAT soil moisture relative index has been converted into a volumetric moisture content, which represents a critical aspect of the comparison, is also described. Results have demonstrated that, after the conversion of the H-SAF estimates into absolute volumetric soil moisture, the two products show a relatively good degree of correlation. Additional factors, such as spatial property features are also preliminary investigated.

This study sought to assess whether transradial intervention, by minimizing access-site bleeding and vascular events, improves outcomes in patients with ST-segment elevation myocardial infarction compared with the transfemoral approach.Bleeding and consequent blood product transfusions have been causally associated with a higher mortality rate in patients with myocardial infarction undergoing coronary angioplasty.We identified all adults undergoing percutaneous intervention for acute myocardial infarction in Emilia-Romagna, a region in the north of Italy of 4 million residents, between January 1, 2003, and July 30, 2009, at 12 referral hospitals using a region-mandated database of percutaneous coronary intervention procedures. Differences in the risk of death at 2 years between patients undergoing transfemoral versus transradial intervention, assessed on an intention-to-treat basis, were determined from vital statistics records and compared based on propensity score adjustment and matching.A total of 11,068 patients were treated for acute myocardial infarction (8,000 via transfemoral and 3,068 via transradial route). According to analysis of matched pairs, the 2-year, risk-adjusted mortality rates were lower for the transradial than for the transfemoral group (8.8% vs. 11.4%; p = 0.0250). The rate of vascular complications requiring surgery or need for blood transfusion were also significantly decreased in the transradial group (1.1% vs. 2.5%, p = 0.0052).In patients undergoing angioplasty for acute myocardial infarction, transradial treatment is associated with decreased 2-year mortality rates and a reduction in the need for vascular surgery and/or blood transfusion compared with transfemoral intervention.

Background: Despite the well-known prognostic impact of systolic dysfunction in unselected patients undergoing percutaneous coronary intervention (PCI), limited data are available on its current predictive role after PCI for unprotected left main disease (ULM). We thus appraised the prognostic role of left ventricular ejection fraction (LVEF) in patients undergoing PCI for ULM with drug-eluting stents (DES). Methods: Consecutive eligible subjects were retrospectively enrolled in a national registry. Patients were divided into three groups: LVEF < 30%, LVEF 30-45%, and LVEF > 45%. Relevant baseline and outcome data were compared with bivariate and multivariable tests. Results: A total of 975 subjects was included (LVEF < 30%: 46, LVEF 30-45%: 208, LVEF > 45%: 721). Patients with LVEF < 30% had several other unfavorable clinical features, including older age and higher EuroSCORE. Adverse event rates were different already at 7 days (p = 0.012 for all-cause death and p = 0.015 for major adverse cardiac events [MACE]), with even more significant trends up to 30 days and at long-term (p < 0.001 for death, and p < 0.001 for MACE). After a median of 18 months, risk of death totaled 39 versus 13 versus 8% (p < 0.001) and risk of MACE 44 versus 24 versus 22% (p = 0.003). Multivariable analyses showed however that reduced LVEF was not an independent predictor of adverse events at any time-point. Conclusions: Whereas reduced LVEF is apparently a significant predictor of adverse events after PCI with DES for ULM, its prognostic impact is mostly due to clustering with other adverse feature

The enzyme Nicotinamide N-methyltransferase (NNMT) catalyzes the methylation of nicotinamide and other pyridines, playing a pivotal role in the biotransformation and detoxification of many drugs and xenobiotic compounds. Several tumours have been associated with abnormal NNMT expression, however its role in tumour development remains largely unknown. In this study we investigated expression levels of Nicotinamide N-methyltransferase in a cancer cell line and we evaluated the effect of shRNA-mediated silencing of NNMT on cell proliferation. Cancer cells were examined for NNMT expression by semiquantitative RT-PCR and Western blot analysis. A HPLC-based catalytic assay was performed to assess enzyme activity. Cells were transfected with four shRNA plasmids against NNMT and control cells were treated with transfection reagent only (mock). The efficiency of gene silencing was detected by Real-Time PCR and Western blot analysis. MTT cell proliferation assay and the soft agar colony formation assay were then applied to investigate the functional changes in cancerous cell. NNMT mRNA was detected in cancer cells, showing a very high expression level. In keeping with the results of RT-PCR analysis, the protein level and NNMT enzyme activity were particularly high in KB cells. ShRNA vectors targeted against NNMT efficiently suppressed gene expression, showing inhibition observed at both the mRNA and protein levels. Down-regulation of NNMT significantly inhibited cell proliferation and decreased colony formation ability on soft agar. The present data support the hypothesis that the enzyme plays a role in tumour expansion and its inhibition could represent a possible molecular approach to the treatment of cancer.

β- and γ-catenin are components of catenin family involved in cadherin adhesion function. Recently it has been shown that this family is involved in other functions such as signaling and activation of transcription factors. The final goal of this study was to evaluate the role of β- and γ-catenin in bone cell physiology and bone regeneration. Formalin-fixed-paraffin embedded specimens of 15 human bone specimens after sinus lift were collected and examined by immunohistochemstry using primary antibodies against β- and γ-catenin. Staining intensity and cellular localization were evaluated. β and γ-catenin showed a very high level of expression in human bone tissues. In particular catenins were expressed in cells with morphological findings of osteoblasts in the areas of new bone formation at the junction between mineralized and unmineralized tissue, between osteoid matrix and bone. Osteoclasts showed also positivity for catenins. Osteocytes, cells located in lacunae of mature mineralized bone with function of bone vitality maintenance, showed no expression for catenins. Specimens characterized by high amount of catenins in osteoblasts at 1° month showed high grade of bone maturation at 3° month. Data demonstrated an overall involvement of catenins in human bone tissues and in particular during bone regeneration process. The presence of staining for β- and γ-catenin particularly in osteoblasts demonstrates a significant role of catenins in functions, other than in cadherin interaction, such as signaling and activation of transcription factors during differentiation of bone tissues.

This study aims to evaluate whether results of "off-hours" and "regular-hours" primary angioplasty (primary percutaneous coronary intervention [pPCI]) are comparable in an unselected population of patients with ST-segment elevation acute myocardial infarction treated within a regional network organization.Conflicting results exist on the outcome of off-hours pPCI.We analyzed in-hospital and 1-year cardiac mortality among 3,072 consecutive ST-segment elevation myocardial infarction (STEMI) patients treated with pPCI between January 1, 2004, and June 30, 2006, during regular-hours (weekdays 8:00 AM to 8:00 PM) and off-hours (weekdays 8:01 PM to 7:59 AM, weekends, and holidays) within the STEMI Network of the Italian Region Emilia-Romagna (28 hospitals: 19 spoke and 9 hub interventional centers).Fifty-three percent of patients were treated off-hours. Baseline findings were comparable, although regular-hours patients were older and had more incidences of multivessel disease. Median pain-to-balloon (195 min, interquartile range [IQR]: 140 to 285 vs. 186 min, IQR: 130 to 280 min; p = 0.03) and door-to-balloon time (88 min, IQR: 60 to 122 vs. 77 min, IQR: 48 to 116 min; p0.0001) were longer for off-hours pPCI. However, unadjusted in-hospital (5.8% off-hours vs. 7.2% regular-hours, p = 0.11) and 1-year cardiac mortality (8.4% off-hours vs. 10.3% regular-hours, p = 0.08) were comparable. At multivariate analysis, off-hours pPCI did not predict an adverse outcome either for the overall population (odds ratio [OR]: 0.70, 95% confidence interval [CI]: 0.49 to 1.01) or for patients directly admitted to the interventional center (OR: 0.79, 95% CI: 0.52 to 1.20).When pPCI is performed within an efficient STEMI network focused on reperfusion, the clinical effectiveness of either off-hours or regular-hours pPCI is comparable.

Aims: Percutaneous coronary intervention (PCI) is increasingly being used for unprotected left main (ULM) disease. Limited data are available on sex-related differences in this setting. We investigated gender-associated differences in patients undergoing stent-based PCI for ULM. Methods and results: We analysed baseline, procedural and long-term data of patients with ULM undergoing stent-based PCI at participating centres. The primary end-point was the long-term rate of major cardiovascular events rate (MACE, i.e., the composite of death, myocardial infarction, or target lesion revascularisation). The study population included 1,452 cases, with 27.8% females and 72.2% males. Women were older, more frequently diabetic, hypertensive or presenting with an acute coronary syndrome, and thus with a higher EuroSCORE, but were less commonly treated with drug-eluting stents (DES), in comparison to men (all p

In 20 patients with recurrent episodes of lone paroxysmal atrial fibrillation we assessed the onset pattern of each episode of either atrial fibrillation or of atrial flutter during a 24-h Holter monitoring. We evaluated 24 twenty-four-hour Holter tape recordings and our data are related to 168 episodes of paroxysmal atrial fibrillation and 27 episodes of paroxysmal atrial flutter. Eighty-five percent of atrial fibrillations and 67% of atrial flutters were of short duration (less than 5 min). The majority of patients (80%) had either nocturnal or daily episodes of arrhythmia and PP intervals immediately before onset of arrhythmia did not show significant variations in 77% of cases. The coupling interval of the supraventricular premature beats eliciting atrial fibrillation was significantly shorter than the coupling intervals of the spontaneous isolated supraventricular premature beats (p less than 0.0001); again, in 6 patients with either atrial fibrillation or flutter, the coupling interval at onset of fibrillation was significantly shorter in comparison to flutter (p less than 0.0001). In conclusion, vagal or sympathetic prevalence does not seem to influence significantly the beginning of the arrhythmia, while the coupling interval of the atrial premature beats plays a critical role in the inducibility of atrial flutter or fibrillation.

Craniofacial morphology of patients with nevoid basal cell carcinoma syndrome (NBCCS) has sometimes been reported at clinical examination, but any investigation has described it on the basis of cephalometric measurements.The purpose of this study was to conduct a cephalometric analysis of patients with NBCCS and to compare measurements with non-NBCCS subjects of similar ages, to elucidate if there is any relationship between NBCCS and craniofacial morphology.The study population consisted of 14 adult patients (9 men and 5 women), ranging in age from 18.2 to 56.8 years, with the diagnosis of NBCCS, with good-quality lateral cephalometric radiographs, and 14 adult healthy patients matched for age and sex to the NBCCS group. Cephalometric measurements were carried out on radiographs, and measurements of angles and distances were performed.Statistical differences between NBCCS subjects and controls were observed. Data analysis displayed that the measurements of the anterior cranial base (P

Purpose: Survivin, an inhibitor of apoptosis protein and a cell cycle regulator, has been detected in the majority of human cancers. Five splice variants (survivin, survivin-2α, survivin-2B, survivin-3B, and survivin-ΔEx3) have been identified; their expressions have been investigated here. Methods: By means of RT real-time PCR and immunohistochemistry, we have evaluated survivin isoform expressions at both mRNA and protein levels in human normal oral tissue, precancerous lesions, and oral squamous cell carcinoma (OSCC). Their correlations with the pathological findings have also been analyzed. Results: Expression levels of all survivin transcript variants were markedly elevated in OSCC when compared to normal tissues. One-way analysis of variance (ANOVA) revealed highly significant up-regulation of survivin (P = 0.001), survivin-ΔEx3 (P = 0.001) and survivin-2B (P = 0.004), whereas survivin-3B showed a minor increase in OSCC compared to normal mucosa. Conclusions: Our findings suggest that survivin isoforms deregulation may have significant implications in tumor aggressiveness and prognosis. © 2008 Springer-Verlag.

Head and neck cancer is the eighth most common cause of cancer death worldwide. Its incidence varies widely among different regions. In North America and the European Union, head and neck cancer accounts for 3% to 4% of all cancer diagnoses. Conversely, in Southeast Asia and Africa, head and neck cancer accounts for approximately 8% to 10% of all cancers1. Although the incidence of head and neck cancers has decreased slightly from 1975 to 2002 in the United States5, approximately 46 000 new cases are still expected in 2007 alone. Even if surgery and radiotherapy have remained the core therapy in squamous cell carcinoma of the head and neck (HNSCC). Radiotherapy following surgery was the standard approach to the treatment of locoregionally advanced (LA-HNSCC) resectable disease. However, some recent developments highlighted the expanding role of chemotherapy, which is increasingly being incorporated in the management of HNSCC. Concurrent chemo-radiotherapy has shown benefits in randomized trials; in addition, chemotherapy is used by itself as palliative therapy for patients with metastatic disease. As our understanding of the molecular and cellular mechanisms involved in cancer development improves, we are better able to identify potential targets for biological therapy and to apply novel strategies to the preclinical study and clinical treatment of head and neck cancers. Current avenues of research, focusing on clinical studies evaluating antibody directed therapies and gene replacement strategies for head and neck cancer are discussed

The long-term safety and efficacy of drug eluting stents (DES) implanted during primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) is unclear. The purpose of this study was to compare the long-term outcome of STEMI patients undergoing primary PCI with DES vs. bare metal stent (BMS) implantation.In the present analysis 4764 patients were enrolled (706, 15%, received DES). We assessed the cumulative incidence of major adverse cardiac events (MACE) and stent thrombosis (ST).Overall, no significant difference emerged for the rates of death and reinfarction. DES implantation was associated to a reduction of target vessel revascularization (TVR) (HR 0.65, 95%CI 0.47-0.91; p=0.01), leading to a MACE reduction (HR 0.7, 95%CI 0.56-0.86; p0.01). In particular, during the first 2 years we observed less adverse events in the DES group, mainly because of a lower TVR rate (TVR: HR 0.56, 95%CI 0.37-0.83, p0.01; MACE: HR 0.71, 95%CI 0.54-0.94, p=0.01). On the contrary, during the third year, adverse events tended to be higher in the DES group. ST did not differ between DES and BMS groups (p=0.6). No differences were observed between sirolimus eluting stents and paclitaxel eluting stents.DES implantation during primary PCI is safe and associated with a significant TVR and MACE reduction in the first two years, whereas a trend to have more adverse events in the third year is observed. More data about long-term follow-up are needed to better evaluate both safety and efficacy of DES in the setting of STEMI.

Data are limited about the relative efficacy of drug-eluting stents (DESs) versus bare-metal stents (BMSs) for the treatment of unprotected left main coronary artery (ULMCA) stenosis. The survey promoted by the Italian Society of Invasive Cardiology on ULMCA stenosis was an observational study involving 19 high-volume Italian centers of patients with ULMCA stenosis treated using percutaneous coronary intervention (PCI). From January 2002 to December 2006, of 1,453 patients identified with ULMCA stenosis treated with PCI, 1,111 were treated with DESs and 342 were treated with BMSs. During a 2-year follow-up, risk-adjusted survival free from cardiac death was significantly higher in patients treated with DESs than in those treated with BMSs. The propensity-adjusted hazard ratio for risk of 2-year cardiac mortality after DES versus BMS implantation was 0.49 (95% confidence interval 0.32 to 0.77). The benefit of DESs in reducing cardiac mortality was obtained in the period from 3 to 6 months and maintained up to 2 years. In conclusion, for patients with ULMCA stenosis undergoing PCI, DES implantation was associated with higher adjusted rates of 2-year survival free from cardiac death. The benefit of DESs in reducing cardiac mortality was obtained in the period in which clinical manifestations of restenosis usually peak.

Aims In this study, we compared the clinical outcomes of elderly patients with unprotected left main coronary artery (ULMCA) stenosis treated with either coronary artery bypass grafting (CABG) or drug-eluting stent (DES). Methods and results From January 2003 to April 2006, 259 patients with ULMCA stenosis and age ≥75 years underwent coronary revascularization with either CABG or DES. One hundred and sixty-one patients were treated with CABG and 98 with DES. The cumulative unadjusted rates of 2-year mortality were 17% in CABG-treated patients and 18% in those treated with DES ( P = 0.71). The adjusted rates of 2-year survival were 85% for CABG-treated patients and 87% for DES-treated patients ( P = 0.74). The incidence of 2-year myocardial infarction was 6% in CABG-treated patients and 4% in DES-treated patients ( P = 0.11). The incidence of target lesion revascularization (TLR) was 3% in CABG-treated patients and 25% in DES-treated patients ( P < 0.0001). In the multivariable analysis, peripheral vascular disease, left ventricular ejection fraction and acute coronary syndrome were independent predictors of 2-year mortality. Conclusion In this study, we could not demonstrate a difference in mortality between CABG-treated patients and those treated with DES. However, the rate of TLR was higher in the DES group.

The mucosa around implants and the gingiva around teeth respond to plaque formation with the development of an inflammatory lesion which has similar magnitude and histological features. Different cell types in inflamed and healthy periodontal and peri-implant tissues are capable of producing a variety of important pro-inflammatory and anti-inflammatory cytokines and growth factors which mediate the host response. The aim of this study is to compare the expression levels of anti-inflammatory cytokines detectable in the peri-implant soft tissue of two single-implant crowns supported either by zirconia or titanium abutments. Two frozen samples of peri-implant soft tissue of two single-implant crowns supported either by zirconia or titanium abutments were treated to obtain mRNA. The mRNA extracted from these specimens was converted in cDNA and analyzed with “SuperArray GEArray Q Series Human Inflammatory Cytokine/Receptor Gene Array kit”, planned for studying 96 genes involved in inflammatory response. Data showed that gene expression levels of anti-inflammatory cytokines were higher in specimens sampled from the zirconia abutment compared with those from the titanium abutment. It was considered important to detect the mRNA levels of the anti-inflammatory mediators in healthy peri-implant tissues to verify the biological tolerability of zirconia compared with titanium abutments. The difference detected in cytokine expression could be due to the intrinsic biological tolerability of zirconia ceramics or to a lesser bacterial accumulation.

We present a new treatment algorithm aimed to assist surgeons to develop a rational diagnostic protocol and establish effective conservative surgical management in patients with mandibular ameloblastoma. Fifteen consecutive cases treated by conservative management were reviewed. Data collected included age, sex, symptoms and signs at diagnosis, anatomical distribution of the lesions, numbers and types of operations, number of recurrences, and duration of follow-up post-operatively. Curettage was the first operation for all patients and they were closely followed-up post-operatively. During the follow-up period (4-10 years), small recurrences were diagnosed early in 7 patients who were treated by radical surgery including marginal or "box" resection. No further recurrences were observed after the second operation. When detected early, recurrences are small and surrounded by a large amount of uninvolved normal bone so it is possible to manage them with a radical resection, so lowering the risk of further recurrence and avoiding severe cosmetic and functional problems.

We compared the clinical outcome of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in a real-world scenario.In selected patients, SES has been associated with lower late luminal loss than PES. Whether this emerging biological difference could translate into different clinical efficacy in daily practice is presently unknown.This analysis included 1,676 consecutive patients with de novo coronary lesions treated solely with drug-eluting stents (SES = 992; PES = 684). All patients were enrolled in a dynamic prospective registry comprising 13 hospitals. We assessed the cumulative incidence of major adverse cardiac events (MACE), defined as death, myocardial infarction (MI), and target vessel revascularization (TVR) during follow-up.Overall, 29% of the patients had diabetes, 23% had prior MI, and 9% had poor left ventricular function. ST-segment elevation MI was diagnosed at admission in 12%. Multivessel intervention was performed in 16%. At 1-year follow-up, SES was associated with a reduced incidence of MACE (9.2% SES vs. 14.1% PES; p = 0.007) and TVR (5.0% SES vs. 10.0% PES; p = 0.0008) compared to PES. A propensity analysis with many clinical and angiographic variables was carried out to adjust for baseline differences. In this analysis, SES was associated with a 44% risk reduction of MACE (hazard ratio 0.56, 95% confidence interval 0.39 to 0.78) and a 55% reduction of TVR (hazard ratio 0.45, 95% confidence interval 0.29 to 0.70). This result was consistent across most subgroups tested. Similar rates of death and MI were observed in the 2 treatment groups.In this large real-world population, SES improved 1-year clinical results as compared to PES.

We investigated mRNA expression of the genes involved in the apoptotic mechanism in oral squamous cell carcinoma (OSCC) by cDNA microarray. The aim of this study was to identify genes mainly involved in tumorigenesis, comparing the difference of gene expression in neoplastic and non-neoplastic tissues. Eight frozen samples of OSCC and the corresponding normal oral mucosa were treated to obtain mRNA. The mRNA extracted from these specimens was converted into cDNA and analyzed with “SuperArray GEArray Q Series Human Apoptosis Gene Array kit”. Our results showed that in OSCC there is a different expression of CRADD, FADD, ATM and APAF-1 genes compared to normal mucosa. Real-Time PCR, and Western blot analysis were performed on a separate cohort of patients in order to confirm the results obtained by DNA microarray. Our analysis of apoptotic process through microarray technology confirmed that different molecules could be responsible or favour the imbalance of apoptosis in cancer tissues. Microarray technology has made it possible to analyze the expression of multiple genes in a single experiment. However, most commercial array kits, designed to include as many genes as possible, produce a vast amount of data that often is difficult to interpret. In addition, the cost of equipment is often prohibitive. In contrast, the focused kit used was a complete, affordable and effective method to improve knowledge of molecular specific pathways.

Thirty-eight patients with lone paroxysmal atrial fibrillation (PAF) were monitored during spontaneous sleep. The starts of 111 episodes of atrial fibrillation (AF) occurred in 12 patients. Statistical analysis failed to disclose significant differences in the number of starts per hour between wakefulness and the different sleep stages. Heart rate (HR) in the 60 seconds prior to a PAF episode did not show significant changes with respect to fragments of recording taken away from PAF episodes. As expected, spectral analysis of HR variability during sleep (basal values) showed a reduction of low frequency/high frequency (LF/HF) ratio during slow sleep, while the ratio returned to values similar to wake levels during REM sleep. In the 2 minutes preceding a PAF episode the LF/HF ratio of the spectral power was more unstable with a clear-cut prevalence of sympathetic activity both in wake and in different sleep stages. A shift toward parasympathetic activation was never seen before the start of any of the 17 PAF episodes recorded during sleep.

p63 belongs to a protein family that includes 2 structurally related proteins, p53 and p73. The aim of this study was to investigate the biologic role of p63 in oral tumorigenesis and its possible role as prognostic marker in oral cancer. Ninety-four cases of oral squamous cell carcinoma and 10 cases of normal mucosa were analyzed for p63 expression by immunohistochemistry. Normal oral mucosa showed a basal and parabasal expression of p63. Five (5.3%) cases of oral cancer showed less than 10% of positive tumor cells; in 33 (35.1%) cases the positive tumor cells comprised between 10% and less than 30%, in 36 (38.3%) cases the positive tumor cells comprised between 30% and less than 50%, and in 20 (21.3%) cases the positive tumor cells were more than 50%. There was also a statistically significant correlation between p63 expression and tumor differentiation: p63 expression was amplified in poorly differentiated tumors (P < .05). When analyzed for prognostic significance, patients with perineural infiltration had poorer survival rates than the group with no perineural infiltration (P < .05) and patients with increased p63 expression had poorer survival rates than the group with reduced p63 expression (P < .05). The statistical analysis showed no significant correlation between p63 expression, sex, age, tumor size, staging, recurrence, and metastasis. Cases with diffuse p63 expression were more aggressive and poorly differentiated and related to a poorer prognosis. These data suggest that p63 expression may be useful to identify cases of oral squamous cell carcinoma with more aggressive and invasive phenotype providing novel diagnostic and prognostic information on individual patient survival with oral cancers.

A total of 123 cases of odontogenic cysts, distributed as follows: 30 follicular (FC), 35 radicular (RC), 53 keratocysts, 1 glandular odontogenic and 4 calcifying odontogenic cysts, were analysed by immunohistochemistry for expression of p63, a component of p53 protein family. In RCs p63 positivity was not only in basal and parabasal layers but also in the intermediate layer and about 1/3 of cases displayed a percentage of stained cells comprised between 0 and5%, and about 2/3 between5% and50%. In FCs positivity was confined to basal and parabasal layers of the epithelium and in the majority of FCs the stained cells were comprised between 0 and5%. OKCs displayed the most intense and diffuse p63 labeling. In conclusion, these data suggest that p63 expression may be useful to identify cysts type with more aggressive and invasive phenotype supporting the hypothesis of a suprabasal proliferative compartment in OKCs.

We report the clinical, radiographic and histological features of 15 paradental cysts of the first and second molars and recommend conservative surgical treatment. Twelve young patients were operated on for 15 paradental cysts of the first and second molars, and had conservative operations with partial preservation of the mandibular cortical bone. After 2 years there had been no recurrences. The differential diagnosis of paradental cyst was fundamental to allow the correct treatment and the early diagnosis of lesions on the opposite side. The maintenance of periodontal hygiene in the immediate and late postoperative periods was an aid to ensure complete remission of the lesions.

Tako-tsubo syndrome is a clinical entity of transient left ventricular apical ballooning, frequently precipitated by a stressful event. The syndrome can be complicated by left ventricular outflow tract (LVOT) obstruction and can be recurrent. Herewe describe a case of a 64 years old female who had two episodes of tako-tsubo syndrome characterized by a similar stressful event and similar clinical and instrumental characteristics. Apical ballooning syndrome (or Tako-tsubo cardiomyopathy) is a clinical entity characterized by acute but rapidly reversible left ventricular (LV) systolic dysfunction. Recurrence of Tako-stubo syndrome is not frequent as well as LVOT obstruction, mitral regurgitation and shock. We describe a case of recurrent tako-tsubo cardiomyopathy with recurrence of LVOT obstruction and mitral regurgitation and complicated by cardiogenic shock. A 64 years old female with hypertension and chronic obstructive pulmonary disease (COPD) was admitted to the hospital in June 2005 with an acute recurrent chest pain. The patient was on cortisone from 24 h before because of an asthma exacerbation and she reported having also vomit and fright. The clinical symptom started in the morning but she had the first medical contact only in the evening. At the admission in intensive care unit (ICU) the patients was asymptomatic, the electrocardiogram (ECG) showed a 1.5 mm ST elevation from V3 to V6, DI, DII and aVL. Systolic blood pressure was 90 mm Hg, and an echocardiography exam showed an apical ballooning of the left ventricle with moderate mitral regurgitation secondary to left ventricular outflow tract (LVOT) obstruction (Fig. 1). Promptly, glycoprotein inhibitors and heparine were started and coronary angiography was performed the day after. Ventriculography confirmed the apical ballooning and normal coronary artery. Left ventricular ejection fraction (LVEF) was 35% (Fig. 2). The peak of plasma MB-creatinine kinase and of troponin I was 28.5 ng/mL and 6.9 ng/mL respectively. The systolic pressure remained stable at 90 mm Hg for four days with gradually recover until 110 mm Hg. The patient had no signs of congestive heart failure and was discharged after six days. Complete normalization of LVEF was documented at the follow-up. In December 2009 the woman was admitted in hospital for an exacerbation of her COPD. She was treated for eight days with cortisone, ipratropium, salmeterol and antibiotics with a good clinical response. During her stay she presented chest pain and the ECG showed a 2.5 mm STelevation fromV3 to V6, DI and aVL. The coronary angiography showed no obstructive coronary lesions and an apical ballooning aspect at the ventriculogram (Fig. 3). In ICU the patient developed a cardiogenic shock (initial systolic blood pressure of 90 mm Hg with rapid deterioration until 60 mm Hg). An urgent echocardiogram showed the apical ballooning with the concomitance of LVOT obstruction, systolic anterior motion of mitral valve and severe mitral regurgitation (Figs. 3 and 4). Peak dynamic intraventricular pressure gradient detected by echocardiography was 80 mm Hg. The LVEF was 25%. Urgently an intra-aortic balloon pump (IABP) was placed and then she was treated with low-dose beta-blockers until restoration of good pressure and initial recovery of LVEF. After a period of seven days the IABP was removed: the LVEF was 35% and the peak dynamic pressure gradient was lower (12 mm Hg). The peak of plasma MB-creatinine kinase and troponin T was 18.07 μg/L and 0.55 μg/L respectively. She was discharged after other eight days with a good pressure, no sign of congestive heart failure, a LVEF of 48% and absence of sign of LVOT obstruction and mitral regurgitation. Normalization of LVEF was after documented. Tako-tsubo syndrome, which is also called stress cardiomyopathy or transient left ventricular apical ballooning syndrome, is a clinical entity frequently precipitated by a stressful event. Initially, the syndrome was described in Japanese and afterwards an increasing number of cases has been reported also in Caucasian [1,2]. The main features are the absence of coronary atherosclerosis disease and the reversibility of left ventricular dysfunction. Recurrence of Tako-tsubo syndrome is not frequent. The yearly recurrence rate is 2.9% over the first few years, subsequently decreasing to 1.3% per year [3,4]. The syndrome can be also complicated by LVOT obstruction as previously described [5]. The report described is a rare case of recurrent Tako-Tsubo syndrome with recurrence of similar clinical and instrumental signs. In both episodes the main common findings were hypotension and an echocardiographic aspect of LVOT obstruction, systolic anterior motion and secondary mitral regurgitation. The recurrent episode was much more severe with a cardiogenic shock requiring the IABP positioning. Furthermore the patients experienced in both cases the same physical stressful event.

In eight patients (age 62 ± 6 years) a DDDR pacemaker was implanted for sick sinus syndrome (three cases) or second- and third-degree AV block (five cases). In five subjects chronotropic incompetence (maximal heart rate on effort < 110 beats/min) was present before implantation. One month after implantation the patients were randomized to DDDR or DDD pacing for 3 weeks each, with subsequent crossover, and at the end of each period a symptom limited Cardiopulmonary exercise test (25 watts/2 min) was performed and the patients were requested to fill a symptoms questionnaire. Results: DDDR pacing, compared to DDD, was associated with higher maximal heart rates (127 ± 20 vs 110 ± 27 beats/min, P < 0.02), higher (VO2 max (25.4 ± 6.1 vs 21.5 ± 7.8 mL/kg/per min, P < 0.03) and higher VO2 at the anaerobic threshold (20.3 ± 5.0 vs 15.8 ± 4.9 mL/kg per min, P < 0.03), without significant differences in mean exercise time (526 ± 193 vs 472 ± 216 sec, NS). The increase in VO2 max obtained in DDDR versus DDD was significantly related to the increase in maximal heart rate (r = 0.72, P < 0.05) and the increase in VO2 at the anaerobic threshold obtained in DDDR versus DDD was related to the increase in heart rate at the anaerobic threshold (r = 0.81, P < 0.02). In patients with chronotropic incompetence the improvement obtained in DDDR versus DDD was even more significant (VO2 max = 22.7 ± 5.9 vs 16.1 ± 4.4 mL/kg per min, P < 0.03; VO2 at the anaerobic threshold = 18.4 ± 5.1 vs 13.2 ± 2.8 mL/kg per min, P < 0.05; exercise time = 438 ± 132 vs 352 ± 150 sec, P < 0.02). In the population as a whole, no significant differences were found relative to subjective symptoms, meanwhile in patients with chronotropic incompetence a better subjective tolerance was apparent with DDDR than with DDD pacing. In conclusion, DDDR pacing induces a significant improvement of exercice capacity, in comparison to DDD pacing, related to the ability to reach higher heart rates during exercise. This phenomenon is particulary evident in patients with chronotropic incompetence in whom DDDR pacing also is subjectively better tolerated.

Since Raloxifene, a drug used in osteoporosis therapy, inhibits the osteoclast functions but not osteoblast functions, it could improve the recovery during implant surgery. This preliminary report describes a simple method to link, through a covalent bond, Raloxifene to titanium by interfacing with (3-aminopropyl)-Triethoxysilane as assessed by the IR-FT and SEM. To evaluate the biological response of osteoblast-like cells to this implant, we compared expression gene profiling of cell cultures on Raloxifene conjugated implant and normal implant by DNA microarray. By using DNA microarrays containing 19,200 genes, we identified differently expressed genes in osteoblast-like cell line (MG-63). Surface Raloxifene conjugated implants have been shown to have a relevant importance in modifying cell response. This result could be an interesting starting point for the use of an immediate functional loading of implants.

Background Oral squamous cell carcinoma (OSCC) represents the most common oral malignancy. Despite recent advances in therapy, up to 50% of the cases have relapse and/or metastasis. There is therefore a strong need for the identification of new biological markers able to predict the clinical behaviour of these lesions in order to improve quality of life and overall survival. Among tumour progression biomarkers, already known for their involvement in other neoplasia, a crucial role is ascribed to the urokinase-type plasminogen activator receptor (uPAR), which plays a multiple role in extracellular proteolysis, cell migration and tissue remodelling not only as a receptor for the zymogen pro-uPA but also as a component for cell adhesion and as a chemoattractant. The purpose of this study was to gain information on the expression of uPAR in OSCC and to verify whether this molecule can have a role as a prognostic/predictive marker for this neoplasia. Methods In a retrospective study, a cohort of 189 OSCC patients was investigated for uPAR expression and its cellular localization by immunohistochemistry. As standard controls, 8 normal oral mucosal tissues free of malignancy, obtained from patients with no evidence or history of oral cavity tumours, were similarly investigated. After grouping for uPAR expression, OSCCs were statistically analyzed for the variables age, gender, histological grading (G), tumour size, recurrence, TNM staging and overall survival rate. Results In our immunohistochemical study, 74 cases (39.1%) of OSCC showed a mostly cytoplasmic positivity for uPAR, whereas 115 were negative. uPAR expression correlated with tumour differentiation grade and prognosis: percentage of positive cases was the greatest in G3 (70.4%) and patients positives for uPAR expression had an expectation of life lower than those for uPAR negatives. Conclusion The results obtained in this study suggest a role of uPAR as a potential biomarker useful to identify higher risk subgroups of OSCC patients.

Delay in diagnosing oral squamous cell carcinoma (OSCC) can be still identified as a major cause of its high morbidity and mortality. To date, the early diagnosis for OSCC is mainly based on clinical oral examination and there is an urgent need for reliable markers; thus, advancements in molecular technologies has set the stage for investigating new markers, as well as new diagnostic matrices. The aim of the present study is to investigate the presence of proteomic signatures of OSCC in saliva and their use as potential biomarkers for early and non-invasive diagnosis. Saliva from 45 OSCC patients and 30 healthy controls was analysed by SELDI-TOF mass spectrometry and ProteinChip® technology. A supervised multivariate statistical analysis (Classification and Regression Tree - CART) was used to build models for discriminating between OSCC and controls, and between early (ES-OSCC) and late stage (LS-OSCC) cancers. The peptide with 8041 Da mass was 22-fold more expressed in OSCC, thus being a suitable potential biomarker. Classification and regression analysis allowed to build a model that was capable of correctly classifying all cancers and controls in an independent testing set, using the 8041 m/z peak as splitter. Eleven peaks were also differently expressed between ES-OSCCand LS-OSCC, but, basing on these differences, it was not possible to build an algorithm to predict tumour staging. These findings confirm that saliva proteome in OSCC patients is different from healthy controls and these variations might reflect different stages of disease progression and are worthy of further validation as diagnostic and prognostic biomarkers.

PURPOSE To test in a pig model the biocompatibility and effectiveness of carbon-coated renal and iliac artery stent systems during implantation procedures and at different follow-up periods. MATERIALS AND METHODS Twenty-two miniature pigs received carbon-coated balloon-expandable stainless-steel stents in their renal and iliac arteries. Animals were killed at 7, 30, or 180 days for evaluation of acute, subacute, and chronic biologic response to the implanted devices. Histologic, histomorphometric, and scanning electron microscopy (SEM) analyses were performed to assess inflammatory reaction, endothelialization process, and neointimal growth. RESULTS Forty-four iliac stents and 42 renal stents were successfully implanted. Mural thrombi were not observed by angiography or histologic examinations. Histologically, no significant inflammatory reaction was detected: the stents appeared covered by a thin monolayer of endothelial cells even at 7-day follow-up. The neointima showed homogeneous growth and moderate thickness at 30-day and 180-day explantations (0.09 mm ± 0.06 and 0.15 mm ± 0.13, respectively, for renal arteries; 0.12 mm ± 0.04 and 0.21 mm ± 0.12, respectively, for iliac arteries). Internal and external elastic laminae were intact in 82 of 86 cases (95%) of stent-implanted arteries. Histologic validations were obtained with SEM observations for each follow-up group. CONCLUSIONS This study showed good technical results of deployment of carbon-coated renal and iliac stents and very satisfactory biologic behavior in terms of tissue and hematologic compatibility. The devices do not induce thrombus formation.

AIMS: To evaluate the long-term clinical outcome after drug-eluting stents (DES) implantation, and to test if patient selection could enhance their net clinical benefit. METHODS AND RESULTS: We assessed the incidence of major adverse cardiac events (MACE=death, acute myocardial infarction, and target vessel revascularisation, TVR) and angiographic stent thrombosis (ST) during 3-year follow-up in a prospective multicentre registry. Propensity-score analysis to adjust for different clinical, angiographic and procedural characteristics was performed. Overall, 14,115 patients enrolled in the registry received solely BMS (n=9,565) or DES (n=4,550). The incidence of definite ST was 0.6% for BMS and 1.3% for DES (p=0.003). The propensity-score adjusted incidence of cardiac death and myocardial infarction was similar between the two groups (DES 11.9% vs. BMS 12.1%, HR 0.90, 95% CI 0.77-1.04), whereas DES were associated with lower rates of TVR (DES 11.6% vs. BMS 15.2%, HR 0.67, 95% CI 0.59-0.76). The efficacy of DES in reducing TVR increased with increasing likelihood of TVR at baseline. CONCLUSIONS: The beneficial effect of DES in reducing new revascularisations compared to BMS extends out to three years without a significantly worse overall safety profile. The benefit seems more evident in patients with the highest baseline risk of clinical restenosis.

Background— Distal unprotected left main coronary artery (ULMCA) stenosis represents a technical challenge for interventional cardiologists. In this study, we compared 2-year clinical outcomes of different stenting strategies in patients with distal ULMCA stenosis treated with drug-eluting stents. Methods and Results— The survey promoted by the Italian Society of Invasive Cardiology on ULMCA stenosis was an observational study on patients with ULMCA stenosis treated with percutaneous coronary intervention. In this study, we selected patients with distal ULMCA stenosis treated with drug-eluting stents. Seven hundred seventy-three patients were eligible for this study: 456 were treated with 1 stent (group 1) and 317 with 2 stents (group 2). The primary end point of the study was the incidence of major adverse cardiac events (MACEs), defined as the occurrence of mortality, myocardial infarction, and target lesion revascularization. During a 2-year follow-up, risk-adjusted survival free from MACE was significantly higher in patients in group 1 than in patients in group 2. The propensity-adjusted hazard ratio for the risk of 2-year MACE in patients in group 1 versus group 2 was 0.53 (95% CI, 0.37 to 0.76). The propensity-adjusted hazard ratio for the risk of 2-year cardiac mortality and myocardial infarction in patients in group 1 versus group 2 was 0.38 (95% CI, 0.17 to 0.85). Conclusions— Compared with the 2-stent technique, the 1-stent technique is associated with a better 2-year MACE-free survival. The stenting strategy is a prognostic factor that should be taken into account when deciding the optimal revascularization treatment.