Micro-computed tomographic assessment of dentinal microcrack formation in straight and curved root canals in extracted teeth prepared with hand, rotary and reciprocating instruments.

AIM: To compare microcrack formation in roots of extracted teeth after the shaping of straight and curved root canals with hand, rotary and reciprocating files using micro-computed tomographic (micro-CT) analysis. METHODOLOGY: Thirty straight mandibular incisors and 30 severely curved mesial roots of mandibular molars were randomly divided into 6 experimental groups (n = 10) according to the systems used for the root canal preparation and the root canal curvature: ProTaper Universal for Hand Use (Dentsply Sirona, Ballaigues, Switzerland), HyFlex EDM (Coltene-Whaledent, Altstätten, Switzerland) and Reciproc Blue (VDW, Munich, Germany) files used in mandibular incisors (straight canals) and mesial roots of mandibular molars (curved canals). The roots were imaged with micro-CT scanning at an isotropic resolution of 14 µm before and after root canal preparation, and the cross-sectional images generated were assessed to detect microcracks. RESULTS: All dentinal defects identified after root canal preparation were already present before instrumentation, and no new microcracks were detected. Dentinal microcracks were present in 19% (ProTaper Universal for Hand Use), 11% (Hyflex EDM) and 23% (Reciproc Blue) of the cross-sections when the instrumentation was performed in mandibular incisors. Instrumentation of mandibular molars revealed microcracks in 15% (ProTaper Universal for Hand Use), 16% (Hyflex EDM) and 17% (Reciproc Blue) of the cross-sections. CONCLUSIONS: Preparation of straight and curved root canals with ProTaper Universal for Hand Use, HyFlex EDM and Reciproc Blue systems did not produce microcracks in extracted teeth when evaluated with micro-CT.

Moldless Printing of Silicone Lenses With Embedded Nanostructured Optical Filters.

Optical lenses are among the oldest technological innovations (3000 years ago) and they have enabled a multitude of applications in healthcare and in our daily lives. The primary function of optical lenses has changed little over time; they serve mainly as a light-collection (e.g. reflected, transmitted, diffracted) element, and the wavelength and/or intensity of the collected light is usually manipulated by coupling with various external optical filter elements or coatings. This generally results in losses associated with multiple interfacial reflections, and increases the complexity of design and construction. In this work we introduce a change in this paradigm, by integrating both light-shaping and image magnification into a single lens element using a moldless procedure that takes advantage of the physical and optical properties of mesoporous silicon (PSi) photonic crystal nanostructures. Casting of a liquid poly(dimethyl) siloxane (PDMS) pre-polymer solution onto a PSi film generates a droplet with contact angle that is readily controlled by the silicon nanostructure, and adhesion of the cured polymer to the PSi photonic crystal allows preparation of lightweight (10 mg) freestanding lenses (4.7 mm focal length) with an embedded optical component (e.g. optical rugate filter, resonant cavity, distributed Bragg reflector). Our fabrication process shows excellent reliability (yield 95%) and low cost and we expect our lens to have implications in a wide range of applications. As a proof-of-concept, using a single monolithic lens/filter element we demonstrate: fluorescence imaging of isolated human cancer cells with rejection of the blue excitation light, through a lens that is self-adhered to a commercial smartphone; shaping the emission spectrum of a white light emitting diode (LED) to tune the color from red through blue; and selection of a narrow wavelength band (bandwidth 5 nm) from a fluorescent molecular probe.

The laparoscopic mini-gastric bypass: the Italian experience: outcomes from 974 consecutive cases in a multicenter review.

BACKGROUND: Due to the failure of the "old Mason loop," the mini-gastric bypass (MGB) has been viewed with skepticism. During the past 12 years, a growing number of authors from around the world have continued to report excellent short- and long-term results with MGB. METHODS: One university center, three regional hospitals, and two private hospitals participated in this study. From July 2006 to December 2012, 475 men (48.8 %) and 499 women (51.2 %) underwent 974 laparoscopic MGBs. The mean age of these patients was 39.4, and their preoperative body mass index was 48 ± 4.58 kg/m(2). Type 2 diabetes mellitus (T2DM) affected 224 (22.9 %) of the 974 patients, whereas 291 of the 974 patients (29.8 %) presented with hypertension. The preoperative gastrointestinal status was explored in all the patients through esophagogastroduodenoscopia. The major end points of the study were definitions of both MGB safety and efficacy in the long term as well as the endoscopic changes in symptomatic patients eventually produced by surgery. RESULTS: The rate of conversion to open surgery was 1.2 % (12/974), and the mortality rate was 0.2 % (2/974). The perioperative morbidity rate was 5.5 % (54/974), with 20 (2 %) of the 974 patients requiring an early surgical revision. The mean hospital length of stay was 4.0 ± 1.7 days. At this writing, 818 patients are being followed up. Late complications have affected 74 (9 %) of the 818 patients. The majority of these complications (66/74, 89.1 %) have occurred within 1 year after surgery. Bile reflux gastritis was symptomatic, with endoscopic findings reported for 8 (0.9 %) and acid peptic ulcers for 14 (1.7 %) of the 818 patients. A late revision surgery was required for 7 (0.8 %) of the 818 patients. No patient required revision surgery due to biliary gastritis. At 60 months, the percentage of excess weight loss was 77 ± 5.1 %, the T2DM remission was 84.4 %, and the resolution of hypertension was 87.5 %. CONCLUSIONS: Despite initial skepticism, this study, together with many other large-scale, long-term similar studies from around the world (e.g., Taiwan, United States, France, Spain, India, Lebanon) demonstrated the MGB to be a short, simple, low-risk, effective, and durable bariatric procedure.

Phantomless calibration of CT scans for hip fracture risk prediction in silico: Comparison with phantom-based calibration.

Finite element models built from quantitative computed tomography images rely on element-wise mapping of material properties starting from Hounsfield Units (HU), which can be converted into mineral densities upon calibration. While calibration is preferably carried out by scanning a phantom with known-density components, conducting phantom-based calibration may not always be possible. In such cases, a phantomless procedure, where the scanned subject's tissues are used as a phantom, is an interesting alternative. The aim of this study was to compare a phantom-based and a phantomless calibration method on 41 postmenopausal women. The proposed phantomless calibration utilized air, adipose, and muscle tissues, with reference equivalent mineral density values of -797, -95, and 38 mg/cm3, extracted from a previously performed phantom-based calibration. A 9-slice volume of interest (VOI) centred between the femoral head and knee rotation centres was chosen. Reference HU values for air, adipose, and muscle tissues were extracted by identifying HU distribution peaks within the VOI, and patient-specific calibration was performed using linear regression. Comparison of FE models calibrated with the two methods showed average relative differences of 1.99% for Young's modulus1.30% for tensile and 1.34% for compressive principal strains. Excellent correlations (R2 > 0.99) were identified for superficial maximum tensile and minimum compressive strains. Maximum normalised root mean square relative error (RMSRE) values settled at 4.02% for Young's modulus, 2.99% for tensile, and 3.22% for compressive principal strains, respectively. The good agreement found between the two methods supports the adoption of the proposed methodology when phantomless calibration is needed.

In Silico clinical trial to predict the efficacy of hip protectors for preventing hip fractures.

Osteoporosis is characterized by loss of bone mineral density and increased fracture risk. Reduction of hip fracture incidence is of major clinical importance. Hip protectors aim to attenuate the impact force transmitted to the femur upon falling, however different conclusions on their efficacy have been reported; some authors suggest this may be due to differences in compliance. The aim of this study was to apply an In Silico trial methodology to predict the effectiveness of hip protectors and its dependence on compliance. A cohort of 1044 virtual patients (Finite Element models of proximal femur) were generated. A Markov chain process was implemented to predict fracture incidence with and without hip protectors, by simulating different levels of compliance. At each simulated follow-up year, a Poisson distribution was randomly sampled to determine the number of falls sustained by each patient. Impact direction and force were stochastically sampled from a range of possible scenarios. The effect of wearing a hip protector was simulated by applying attenuation coefficients to the impact force (12.9 %, 19 % and 33.8 %, as reported for available devices). A patient was considered fractured when impact force exceeded the femur strength. Without hip protector, virtual patients experienced 66 ± 5 fractures in 10 years. Wearing the three devices, fracture incidence was reduced to 43 ± 4, 35 ± 4 and 17 ± 2 respectively, at full compliance. As expected, effectiveness was dependent on compliance. This In Silico trial technology can be applied in the future to test multiple interventions, optimise intervention strategies, improve clinical trial design and drug development.

Development and validation of a semi-automated and unsupervised method for femur segmentation from CT.

Quantitative computed tomography (QCT)-based in silico models have demonstrated improved accuracy in predicting hip fractures with respect to the current gold standard, the areal bone mineral density. These models require that the femur bone is segmented as a first step. This task can be challenging, and in fact, it is often almost fully manual, which is time-consuming, operator-dependent, and hard to reproduce. This work proposes a semi-automated procedure for femur bone segmentation from CT images. The proposed procedure is based on the bone and joint enhancement filter and graph-cut algorithms. The semi-automated procedure performances were assessed on 10 subjects through comparison with the standard manual segmentation. Metrics based on the femur geometries and the risk of fracture assessed in silico resulting from the two segmentation procedures were considered. The average Hausdorff distance (0.03 ± 0.01 mm) and the difference union ratio (0.06 ± 0.02) metrics computed between the manual and semi-automated segmentations were significantly higher than those computed within the manual segmentations (0.01 ± 0.01 mm and 0.03 ± 0.02). Besides, a blind qualitative evaluation revealed that the semi-automated procedure was significantly superior (p < 0.001) to the manual one in terms of fidelity to the CT. As for the hip fracture risk assessed in silico starting from both segmentations, no significant difference emerged between the two (R2 = 0.99). The proposed semi-automated segmentation procedure overcomes the manual one, shortening the segmentation time and providing a better segmentation. The method could be employed within CT-based in silico methodologies and to segment large volumes of images to train and test fully automated and supervised segmentation methods.

Statistical Properties of a Virtual Cohort for In Silico Trials Generated with a Statistical Anatomy Atlas.

Osteoporosis-related hip fragility fractures are a catastrophic event for patient lives but are not frequently observed in prospective studies, and therefore phase III clinical trials using fractures as primary clinical endpoint require thousands of patients enrolled for several years to reach statistical significance. A novel answer to the large number of subjects needed to reach the desired evidence level is offered by In Silico Trials, that is, the simulation of a clinical trial on a large cohort of virtual patients, monitoring the biomarkers of interest. In this work we investigated if statistical aliasing from a custom anatomy atlas could be used to expand the patient cohort while retaining the original biomechanical characteristics. We used a pair-matched cohort of 94 post-menopausal women (at the time of the CT scan, 47 fractured and 47 not fractured) to create a statistical anatomy atlas through principal component analysis, and up-sampled the atlas in order to obtain over 1000 synthetic patient models. We applied the biomechanical computed tomography pipeline to the resulting virtual cohort and compared its fracture risk distribution with that of the original physical cohort. While the distribution of femoral strength values in the non-fractured sub-group was nearly identical to that of the original physical cohort, that of the fractured sub-group was lower than in the physical cohort. Nonetheless, by using the classification threshold used for the original population, the synthetic population was still divided into two parts of approximatively equal number.

Deep Learning Method for Estimation of Morphological Parameters Based on CT Scans.

In this study, we propose a Convolutional Neural Network (CNN) with an assembly of non-linear fully connected layers for estimating body height and weight using a limited amount of data. This method can predict the parameters within acceptable clinical limits for most of the cases even when trained with limited data.

MicroRNAs affecting the susceptibility of melanoma cells to CD8+ T cell-mediated cytolysis.

BACKGROUND: The regulatory functions of microRNAs (miRNAs) in anti-tumour immunity have been mainly described in immune effector cells. Since little is known about miRNA effects on the susceptibility of target cells during T cell-target cell interaction, this study focused on the identification of miRNAs expressed in tumour cells controlling their susceptibility to CD8+ T cell-mediated cytotoxicity. METHODS: Luciferase expressing B16F10 melanoma (B16F10 Luci+ ) cells transfected with individual miRNAs covering a comprehensive murine miRNA library were screened for their susceptibility to lysis by an established cytotoxic T lymphocyte (CTL) line (5a, clone Nß) specific for the melanoma-associated antigen tyrosinase-related protein 2. miRNAs with the most pronounced effects on T cell-mediated lysis were validated and stably expressed in B16F10 cells. In silico analyses identified common targets of miRNA sets determined by the screen, which were further confirmed by small interfering RNA (siRNA)-mediated silencing experiments modulating immune surveillance. The Ingenuity Pathway Analysis (IPA) software and RNA sequencing (RNA-seq) data from miRNA-overexpressing cell lines were applied to investigate the underlying mechanisms. The Cancer Genome Atlas (TCGA)-derived miRNA sequencing data were used to assess the correlation of miRNA expression with melanoma patients' survival. RESULTS: The miRNA screen resulted in the selection of seven miRNAs enhancing CTL-mediated melanoma cell killing in vitro. Upon stable overexpression of selected miRNAs, hsa-miR-320a-3p, mmu-miR-7037-5p and mmu-miR-666-3p were determined as most effective in enhancing susceptibility to CTL lysis. In silico analyses and subsequent siRNA-mediated silencing experiments identified Psmc3 and Ndufa1 as common miRNA targets possibly involved in the functional effects observed. The analyses of RNA-seq data with IPA showed pathways, networks, biological functions and key molecules potentially involved in the miRNA-mediated functional effects. Finally, based on TCGA data analysis, a positive correlation of the conserved miRNAs among the panel of the seven identified miRNAs with overall survival of melanoma patients was determined. CONCLUSIONS: For the first time, this study uncovered miRNA species that affect the susceptibility of melanoma cells to T cell-mediated killing. These miRNAs might represent attractive candidates for novel therapy approaches against melanoma and other tumour entities.

Surgical strategy for the treatment of sporadic medullary thyroid carcinoma: our experience.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare disease which accounts for approximately 5-9% of all thyroid cancers and originates from the calcitonin-screening parafollicular C cells. MTC can be divided into two subgroups: sporadic (75%) or inherited (25%). The majority of patients with invasive MTC have metastasis to regional lymph nodes at the time of diagnosis, as evidenced by the frequent finding of persistently elevated calcitonin levels after thyroidectomy and the high rates of recurrence in the cervical lymph nodes reported in retrospective studies. OBJECTIVES: The purpose of the study is to review our single institution's experience with MTC since 1998 and to evaluate surgical strategy, patterns of lymph node metastases and calcitonin response to compartment-oriented lymphadenectomy in patients with primary or recurrent sporadic medullary thyroid carcinoma. METHODS: A retrospective review of 26 patients treated for MTC at the "Antonio Cardarelli" Hospital referral center, in Naples, between 1998 and 2012. There were 18 female and 8 male patients, median age at presentation was 55 years, and median follow-up for survivors was 5 years. Total thyroidectomy was performed in all 26 patients; central compartment (CC) node dissection (level VI) in 12 (46%) patients; central plus lateral compartment (LC) node dissection (levels II, III, and IV) in 7 (27%) patients. 4 patients (15%) underwent reoperation for loco-regional recurrent/persistent MTC. Results. After a median post-surgical follow-up of 5 years (range 1-10 years), 63 % of patients were living disease-free, 15% were living with disease and/or persistently elevated calcitonin levels after surgery, 11% were deceased due to MTC and 11 % were lost to follow-up. CONCLUSIONS: We agree with most authors advocating for a total thyroidectomy and prophylactic central neck dissection in the setting of clinically detected MTC. Lateral neck dissection may be best reserved for patients with positive preoperative imaging. Nevertheless MTC has a high rate of lymph node metastases that are sub optimally detected preoperatively in the central compartment by neck ultrasound or intra-operatively by the surgeon, and reoperation is associated with a higher rate of surgical complications. In our limited experience, patients with thyroid confined nodular pathology, without nodal disease and unknown preoperative diagnosis of MTC, underwent only total thyroidectomy with a good prognosis.

[Management of ascites due to portal hypertension]. / Hypertension portale et prise en charge de l'ascite.

Portal hypertension is regularly encountered by the general practitioner. It is defined by an elevation of the porto-systemic pressure gradient, with complications such as ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, variceal bleeding, hypersplenism, hepatopulmonary syndrome or hepatic encephalopathy occuring when a significant elevation of this gradient is reached. Cirrhosis is the primary cause of portal hypertension in industrialized countries. Symptomatic portal hypertension carries a poor prognosis. Management should be initiated rapidly, including the identification and correction of any reversible underlying condition. Liver transplantation should be considered in advanced cases.

Mindfulness-Based Interventions for Physical and Psychological Wellbeing in Cardiovascular Diseases: A Systematic Review and Meta-Analysis.

BACKGROUND: Recently, there has been an increased interest in the efficacy of mindfulness-based interventions (MBI) for people with cardiovascular diseases (CVD), although the exact beneficial effects remain unclear. METHODS: This review aims to establish the role of MBI in the management of wellbeing for patients with CVD. Seventeen articles have been included in this systematic synthesis of the literature and eleven in the meta-analysis. RESULTS: Considering physical (i.e., heart rate, blood pressure) and psychological outcomes (i.e., depression, anxiety, stress, styles of coping), the vast majority of studies confirmed that MBI has a positive influence on coping with psychological risk factors, also improving physiological fitness. Random-effects meta-analysis models suggested a moderate-to-large effect size in reducing anxiety, depression, stress, and systolic blood pressure. CONCLUSIONS: Although a high heterogeneity was observed in the methodological approaches, scientific literature confirmed that MBI can now be translated into a first-line intervention tool for improving physical and psychological wellbeing in CVD patients.

The Effect of Acceptance and Commitment Therapy for Improving Psychological Well-Being in Parents of Individuals with Autism Spectrum Disorders: A Randomized Controlled Trial.

BACKGROUND: Acceptance and Commitment Therapy (ACT) has been demonstrated as effective in improving psychological well-being in several clinical domains, but there is no evidence regarding the parents of children with Autism Spectrum Disorder (ASD). METHODS: In this randomized controlled trial, we evaluated the efficacy of the ACT matrix behavioral protocol in comparison to the Parent Training (PT) program, measuring several primary and secondary outcomes prior to and following treatments. Twelve parents were randomly and equally assigned to two demographically matched groups wherein individuals underwent 24 weekly meetings of ACT protocol (experimental group) or conventional PT (control group). RESULTS: Parents enrolled in the ACT protocol demonstrated significant improvement in psychological flexibility, awareness states, personal values in everyday life, and parental stress, whereas reduced scores were elicited in parents' perceptions of their child's disruptive behaviors. CONCLUSIONS: The results of this randomized controlled trial, if repeated with a large number of subjects, could open the way to include ACT protocols in daily practice to support the development of new parenting skills.

[Management of chronic hepatitis B]. / Prise en charge de l'hépatite B chronique: un défi en évolution constante.

Chronic hepatitis B predisposes to the development of cirrhosis and hepatocellular carcinoma. Treatment of chronic hepatitis B is aimed at halting viral replication and, thereby, hepatic inflammation. Treatment indication should be established carefully and with full knowledge of the advantages and limitations of currently available antiviral drugs. Patients on long-term nudcleos(t)ide analogue treatment should be followed regularly in order to avoid the appearance of antiviral resistance. The purpose of this review is to provide a concise overview of the diagnosis and management of chronic hepatitis B.

Bioresorbable Materials on the Rise: From Electronic Components and Physical Sensors to In Vivo Monitoring Systems.

Over the last decade, scientists have dreamed about the development of a bioresorbable technology that exploits a new class of electrical, optical, and sensing components able to operate in physiological conditions for a prescribed time and then disappear, being made of materials that fully dissolve in vivo with biologically benign byproducts upon external stimulation. The final goal is to engineer these components into transient implantable systems that directly interact with organs, tissues, and biofluids in real-time, retrieve clinical parameters, and provide therapeutic actions tailored to the disease and patient clinical evolution, and then biodegrade without the need for device-retrieving surgery that may cause tissue lesion or infection. Here, the major results achieved in bioresorbable technology are critically reviewed, with a bottom-up approach that starts from a rational analysis of dissolution chemistry and kinetics, and biocompatibility of bioresorbable materials, then moves to in vivo performance and stability of electrical and optical bioresorbable components, and eventually focuses on the integration of such components into bioresorbable systems for clinically relevant applications. Finally, the technology readiness levels (TRLs) achieved for the different bioresorbable devices and systems are assessed, hence the open challenges are analyzed and future directions for advancing the technology are envisaged.

[Highlights in hepatology]. / Actualités en hépatologie.

This review highlights recent advances in hepatology, including new insights into the clinical penetrance of hereditary hemochromatosis, the development of non-immunosuppressive cyclosporin A analogs for the treatment of chronic hepatitis C, thrombopoietin receptor agonists for thrombocytopenia in cirrhosis, the development of vasopressin V2 receptor antagonists (vaptans) for the management of ascites and hyponatremia in portal hypertension, the description of chronic hepatitis E in immunosuppressed patients, and the development of sorafenib as the first molecularly targeted therapy with a demonstrated benefit in the treatment of advanced hepatocellular carcinoma. These new developments will be summarized and discussed critically, with a particular emphasis on their potential implications for current and future clinical practice.

Decoration of Porous Silicon with Gold Nanoparticles via Layer-by-Layer Nanoassembly for Interferometric and Hybrid Photonic/Plasmonic (Bio)sensing.

Gold nanoparticle layers (AuNPLs) enable the coupling of morphological, optical, and electrical properties of gold nanoparticles (AuNPs) with tailored and specific surface topography, making them exploitable in many bioapplications (e.g., biosensing, drug delivery, and photothermal therapy). Herein, we report the formation of AuNPLs on porous silicon (PSi) interferometers and distributed Bragg reflectors (DBRs) for (bio)sensing applications via layer-by-layer (LbL) nanoassembling of a positively charged polyelectrolyte, namely, poly(allylamine hydrochloride) (PAH), and negatively charged citrate-capped AuNPs. Decoration of PSi interferometers with AuNPLs enhances the Fabry-Pérot fringe contrast due to increased surface reflectivity, resulting in an augmented sensitivity for both bulk and surface refractive index sensing, namely, about 4.5-fold using NaCl aqueous solutions to infiltrate the pores and 2.6-fold for unspecific bovine serum albumin (BSA) adsorption on the pore surface, respectively. Sensitivity enhancing, about 2.5-fold, is also confirmed for affinity and selective biosensing of streptavidin using a biotinylated polymer, namely, negatively charged poly(methacrylic acid) (b-PMAA). Further, decoration of PSi DBR with AuNPLs envisages building up a hybrid photonic/plasmonic optical sensing platform. Both photonic (DBR stop-band) and plasmonic (localized surface plasmon resonance, LSPR) peaks of the hybrid structure are sensitive to changes of bulk (using glucose aqueous solutions) and surface (due to BSA unspecific adsorption) refractive index. To the best of our knowledge, this is the first report about the formation of AuNPLs via LbL nanoassembly on PSi for (i) the enhancing of the interferometric performance in (bio)sensing applications and (ii) the building up of hybrid photonic/plasmonic platforms for sensing and perspective biosensing applications.

A Novel Third Wave Contextual Approach of Positive Behavior Support in School for Adolescent at High Psychosocial Risk: Rationale, Feasibility, and First Pilot Outcomes.

Adolescence is a stage in life when dramatic physical, cognitive and socio-emotional changes occur. When adolescents grow-up in deprived social environments, the chance of psychophysical well-being severely decreases and problems such as delinquency, substance abuse and mental health issues are much more likely to ensue. Third wave cognitive-behavioral interventions are increasingly becoming the chosen instruments to support psychological intervention for young people and adolescents. In this study, we aim to test the feasibility and the adequacy of the outcome measures of an intervention for adolescents at high psychosocial risk, using a modified Discoverer, Noticer, Advisor and Values (DNA-V) protocol aimed at increasing flexible and positive values. The project was conducted in a school located in a low Socio-Economic Status (SES) and severely deprived district of a metropolitan area in Messina, Italy, with 3 classes from 6th to 8th grade. All parents and teachers allowed participants to take part in the pilot study. However, the participants' willingness to engage in the study was low (1 out of 3 classes). Overall, 13 adolescents (72% of the enrolled class) participated in the pilot and only 2 out of 7 teachers and no parents were available for interviews. In its current form, a full RCT is not considered feasible due to general low motivation showed by the participants. Although the sample size was small, the intervention program showed a statistically significant main effect for students' self-report questionnaire, suggesting that those measures were appropriate. Modifications and additional measures are suggested to increase participants' engagement and to overcome the need for parents and teachers' interviews.

[Gastric cancer: surgical treatment and prognostic score]. / Il cancro gastrico: trattamento chirurgico ed elaborazione di un nuovo score prognostico.

AIM: Gastric cancer is the fifth most common cause of tumor-related death in Western countries. Surgery is the only effective treatment but only 50-60% of patients can receive a curative treatment because of absent or aspecific symptoms. The aim of this study was to develop a scale for gastric cancer patients that takes into account factors related to the tumor and to the patient. METHODS: Fifty-seven patients with gastric adenocarcinoma admitted to the Department of General, Geriatric Surgery and Diagnostic and Operative Endoscopy of the University ''Federico II'' in Naples, and treated by gastrectomy from January 1998 until December 2002, were included in this retrospective cohort. The prognostic score was created according to the variables identified in Cox analysis as statistically significant (P 0.1). RESULTS: The 5-year mortality rate was 61%. Cox analysis identified these variables with a significant effect on mortality: age ?60 (odds ratio (OR) 4.16; P=0.015), smoking or alcoholism (OR 2.66; P=0.057), pTNM I (OR 0.04; P=0.003), pTNM II (OR 0.18; P=0.029), pTNM III (OR 0.27; P=0.023), pTNM IV (OR 3.28; P=0.012), lymph node ratio (LNR) <20% (OR 0.15; P=0.01), LNR 20% (OR 3.83; P=0.002), Lauren diffuse histotype (OR 2.41; P=0.1) and location of the neoplasm at superior third (OR 6.70; P=0.003), middle third (OR 5.60; P=0.003), or inferior third (OR 0.32; P=0.008). Patients have been randomized into three groups according to their scores (3-40.5; 41-78.5; 79-115.5) and the 5-year mortality rate was 46%, 59%, 90% in group 1, 2 and 3 respectively. CONCLUSION: It is necessary to consider in prognostic stratification of gastric cancer patients not only pTNM staging but also other factors such as age, smoking or alcoholism, Lauren histotype, location and linfonodal involvement. It is possible to design a more effective prognostic score predicting the individual risk and addressing the therapy and the follow-up.

miR-193b and miR-30c-1* inhibit, whereas miR-576-5p enhances melanoma cell invasion in vitro.

In cancer cells, microRNAs (miRNAs) are often aberrantly expressed resulting in impaired mRNA translation. In this study we show that miR-193b and miR-30c-1* inhibit, whereas miR-576-5p accelerates invasion of various human melanoma cell lines. Using Boyden chamber invasion assays the effect of selected miRNAs on the invasive capacity of various human melanoma cell lines was analyzed. Upon gene expression profiling performed on transfected A375 cells, CTGF, THBS1, STMN1, BCL9, RAC1 and MCL1 were identified as potential targets. For target validation, qPCR, Western blot analyses or luciferase reporter assays were applied. This study reveals opposed effects of miR-193b / miR-30c-1* and miR-576-5p, respectively, on melanoma cell invasion and on expression of BCL9 and MCL1, possibly accounting for the contrasting invasive phenotypes observed in A375 cells transfected with these miRNAs. The miRNAs studied and their targets identified fit well into a model proposed by us explaining the regulation of invasion associated genes and the observed opposed phenotypes as a result of networked direct and indirect miRNA / target interactions. The results of this study suggest miR-193b and miR-30c-1* as tumor-suppressive miRNAs, whereas miR-576-5p appears as potential tumor-promoting oncomiR. Thus, miR-193b and miR-30c-1* mimics as well as antagomiRs directed against miR-576-5p might become useful tools in future therapy approaches against advanced melanoma.