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Chronic Obstructive Pulmonary Disease (COPD) ranks third as cause of mortality and disability-adjusted life years (DALY) worldwide and also in Italy it imposes a huge health, social and economic load. Early symptoms of COPD are often disregarded by patients and physicians, spirometry is underutilized, and the diagnosis is delayed till the disease has reached a distinct severity level. Despite the availability of various guidelines, the behavior of health workers involved in the management of COPD is still rather unlike. These considerations are the reason why in October 2013 AIMAR (Interdisciplinary Scientific Association for Research in Lung Disease) devised and organized a “Third Consensus Conference”, aimed at pointing out the standards of suitability for COPD management. In this context three important topics of discussion were identified: early and more widespread diagnosis, management of acute and subacute phases, long-term assistance to chronic patients. The procedure recommended by the Italian Health Superior Institute (ISS) for Consensus Conferences organization was applied. The Conference was structured in three sessions, each dealing with one of the above mentioned topics and including a short update of the subject-matter and presentation, discussion and voting of some statements with a choice ranging from total agreement to total disagreement or no knowledge. The results of voting were eventually recorded in the document, reviewed by an independent jury, that forms the substance of this paper. The essential role of spirometry, the need for distinguish between different COPD phenotypes, and the obligatoriness to base on the blood gas analysis findings the long-term oxygen therapy, were largely agreed, as well as the need for interventions aimed at decreasing the rate of acute exacerbations. More specific topics like the use of noninvasive ventilation, recognizing the factors affecting outcome and mortality, the choice of pharmacological and non pharmacological treatments in COPD patients led to lively discussing, but they did not always reach the total agreement, probably because of insufficient familiarity with these problems and of diversities in organization and instruments availability. The chronic respiratory assistance was treated with particular regard to smoking cessation, whose implementation is still insufficient. Many doubts rose due to uncertainty, lack of ability and standardization of procedures, insufficient institutional support, and difficulties to realize a network for assistance to chronic patients. The results of this Third Consensus Conference revealed some certainties and many doubts and diversities of view also on topics whose importance is well demonstrated in scientific literature. Thus, there is still a long distance to cover before reaching a suitable standardization of COPD management and such situation urges the need for improving not only the health professional’s operativeness but also the organizational support by competent institutions. In this context some initiatives organized by AIMAR in cooperation with other respiratory scientific societies and patients’ associations are going on.

Introduction:Cyclooxygenase-2 (COX-2) is overexpressed in several malignancies and is implicated in breast cancer progression.Objectives:We investigated whether changes in COX-2 expression may affect epithelial-to-mesenchymal transition (EMT) and then invasive potential of human breast cancer cells, in relationship with hypoxia. COX-2-null MCF-7 human breast cancer cells, MCF-7 cells transiently expressing COX-2 and COX-2-expressing MDA-MB-231 cells were employed.Results:COX-2 overexpression resulted in downregulation of E-cadherin and β-catenin, upregulation of vimentin, N-cadherin and SNAI1, suggesting EMT occurrence. COX-2-overexpressing MCF-7 cells were also characterized by increased invasiveness and release of matrix-metalloproteinase-9. The above-mentioned characteristics, homologous to those detected in highly invasive MDA-MB-231 cells, were reverted by treatment of COX-2-overexpressing MCF-7 cells with celecoxib, a COX-2-specific inhibitor, partly through the inhibition of COX-2-related intracellular generation of reactive oxygen species. Hypoxia further exacerbated COX-2 expression, EMT changes and invasive ability in both COX-2-overexpressing MCF-7 cells and MDA-MB-231 cells. Finally, immunohistochemistry performed on samples from normal and neoplastic human breast tissues revealed that COX-2-positive malignant cells were also positive for EMT-related antigens, hypoxia-inducible factor (HIF)-2α and the oxidative stress marker heme oxygenase.Conclusions:These findings support the existence of a direct link between COX-2 overexpression, EMT and invasiveness in human breast cancer cells, emphasizing the role of hypoxic microenvironment.

Tetrahedral nanopyramids made of silver and gold over ITO/glass surfaces are fabricated. Our protocol is based on nanosphere lithography (NSL) with the deposition of thicker metal layers. After removing the microspheres used in the NSL process, an array of metallic tetrahedral nanostructures of ∼350–400 nm height is formed. The reported procedure avoids the use of any stabilizing surfactant molecules that are generally necessary to segregate the individual particles onto surfaces. We focus here on the optical and the physical properties of these plasmonic surfaces using near-field spectroscopy in conjunction with finite difference time domain (FDTD) modeling of the electric field. Remarkably, FDTD shows that the localized surface plasmon resonance is confined in the plane formed by the edges of two facing pyramids that is parallel to the polarization of the impinging excitation laser. The variable gap between the edges of two adjacent pyramids shows a broader localized surface plasmon and a larger specific surface as opposed to the usual nanotriangle array. Localized enhancement of the electric field is experimentally investigated by coating the plasmonic surface with a thin film of photosensitive azopolymer onto the surface of the nanopyramids. Upon irradiation, the deformation of the surface topography is visualized by atomic force microscopy and suggests the potentiality of these 3D nanopyramids for near-field enhancement. This last feature is clearly confirmed by surface-enhanced Raman scattering measurement with 4-nitrothiophenol molecules deposited on the pyramid platforms. The potentiality of such 3D nanostructures in plasmonics and surface spectroscopy is thus clearly demonstrated.

OBJECTIVE To evaluate the accuracy of liver biopsy findings in preoperative assessment of chemotherapy-associated liver injuries (CALIs). DESIGN Prospective study. SETTING Tertiary care referral hospital. PATIENTS From July 1, 2007, to January 31, 2011, all patients with colorectal metastases receiving preoperative oxaliplatin- and/or irinotecan-based chemotherapy (≥4 cycles) were considered for the present study. Patients underwent parenchymal biopsy before liver resection. Blinded CALI evaluation was performed on biopsy and resection specimens. INTERVENTION Liver resection. MAIN OUTCOME MEASURES Sensitivity, specificity, and accuracy of liver biopsy in CALI evaluation. RESULTS We included 100 patients. At specimen analysis, grade 2 or 3 steatosis was diagnosed in 30 patients; grade 2 or 3 sinusoidal dilatation, in 28; grade 2 hepatocellular ballooning, in 3; grade 2 or 3 lobular inflammation, in 25; and steatohepatitis in 19. Obesity was associated with grade 3 steatosis (20.8% vs 5.3%; odds ratio [OR], 4.74 [P = .03]) and steatohepatitis (33.3% vs 14.5%; OR, 2.96 [P = .04]). Oxaliplatin administration was associated with higher sinusoidal dilatation grade (P = .049). Mortality (2 cases) was increased among patients with steatohepatitis (10.5% vs 0; OR, 13.67 [P = .04]). Biopsy findings correctly predicted steatosis (sensitivity, 88.9%; accuracy, 93.0%) but had low sensitivity and accuracy for sinusoidal dilatation (21.4% and 63.0%, respectively), hepatocellular ballooning (16.0% and 69.0%, respectively), lobular inflammation (20.0% and 78.0%, respectively), and steatohepatitis (21.1% and 79.0%, respectively). Biopsy accuracy did not improve regarding specific chemotherapy regimens or prolonged treatments. CONCLUSIONS Liver biopsy cannot be considered a reliable tool in assessing CALIs except for steatosis. The procedure should not be recommended during preoperative workup.

We describe the synchronous presentation of hepatoid adenocarcinoma of the lung and colorectal adenocarcinoma in a patient with elevated alpha-fetoprotein (AFP) serum levels. Our patient was treated after surgery with a conventional chemotherapy regimen including bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, which was demonstrated to improve the clinical results in the treatment of colorectal and lung cancer compared with chemotherapy alone, and is today approved both for colon and lung cancer.Besides the unconventional association of the two cancer types in our patient and the unsatisfactory clinical benefit obtained with the medical treatment administered, we report on the significance of AFP serum levels as a tumor marker in this peculiar situation. In our patient these levels, monitored from the first clinical symptoms through the last chemotherapy course, did not show any correlation with the response to treatment or with the patient's overall outcome. In particular, the serum marker remained essentially unchanged after the surgical removal of the lung mass and the subsequent chemotherapy.

β2-syntrophin, a dystrophin-associated protein, plays a pivotal role in insulin secretion by pancreatic β-cells. It contains a PDZ domain (β2S-PDZ) that, in complex with protein-tyrosine phosphatase ICA512, anchors the dense insulin granules to actin filaments. The phosphorylation state of β2-syntrophin allosterically regulates the affinity of β2S-PDZ for ICA512, and the disruption of the complex triggers the mobilization of the insulin granule stores. Here, we investigate the thermal unfolding of β2S-PDZ at different pH and urea concentrations. Our results indicate that, unlike other PDZ domains, β2S-PDZ is marginally stable. Thermal denaturation experiments show broad transitions and cold denaturation, and a two-state model fit reveals a significant unfolded fraction under physiological conditions. Furthermore, Tmand Tmaxdenaturant-dependent shifts and noncoincidence of melting curves monitored at different wavelengths suggest that two-state and three-state models fail to explain the equilibrium data properly and are in better agreement with a downhill scenario. Its higher stability at pH >9 and the results of molecular dynamics simulations indicate that this behavior of β2S-PDZ might be related to its charge distribution. All together, our results suggest a link between the conformational plasticity of the native ensemble of this PDZ domain and the regulation of insulin secretion.

We theoretically and experimentally study the structuration of organic solar cells in the shape of photonic crystal slabs. Using a Finite Difference Time Domain (FDTD) method, we investigate the double structuration of the PEDOT:PSS layer and the metallic electrode. By taking advantage of the optical properties of photonic crystals slabs, we show the possibility to couple Bloch modes with very low group velocities in the active layer of the cells. Such Bloch modes, also called slow Bloch modes (SBMs), allow increasing the lifetime of photons within the active layer. We show that an absorption gain ranging between 4% and 11% is possible according to the band gap of the organic material. Finally, we present experimental demonstration performed using nanoimprint to directly pattern the standard organic semiconductor P3HT :PCBM blend in thin film form in the shape of a photonic crystal able to couple SBMs.

Experimental results concerning the influence of plasmon effect from silver nanoparticles on the organic photovoltaic device performance are presented. The metallic nanoparticles (NPs) are placed on top of ITO layer using a physical vapor deposition technique. Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) followed by an interpenetrated poly(3-hexylthiophene): [6,6]-phenyl-C61-butyric acid methyl ester (P3HT:PCBM) blend layer are then spin-coated. The aluminum electrode is finally evaporated on. Photovoltaic properties compared to devices without NPs are shown. A spectrophotometric characterization is carried on. Moreover, a ToF-SIMS measurement is performed in order to obtain the depth chemical profiles of solar cell containing such NPs. Silver NPs diffusion inside other layers of the cell is investigated.

Knowledge-based clinical decision making is one of the most challenging activities of physicians. Clinical Practice Guidelines are commonly recognized as a useful tool to help physicians in such activities by encoding the indications provided by evidence-based medicine. Computer-based approaches can provide useful facilities to put guidelines into practice and to support physicians in decision-making. Specifically, GLARE (GuideLine Acquisition, Representation and Execution) is a domain-independent prototypical tool providing advanced Artificial Intelligence techniques to support medical decision making, including what-if analysis, temporal reasoning, and decision theory analysis. The paper describes such facilities considering a real-world running example and focusing on the treatment of therapeutic decisions.

Objective:COX-2 is implicated in carcinogenesis and tumour progression in many cancers, including breast cancer. Recently, it has been reported that human breast carcinomas aberrantly express COX-2, and that raised tissue levels of COX-2 may have prognostic value. Patients expressing high levels of COX-2 can develop local recurrence, and have reduced disease-free and disease-related overall survival. The aim of this study was to investigate COX-2 expression in human ductal and lobular breast cancers and its possible association with clinicopathological features and prognostic molecular markers.Research design and methods:Cytoplasmic COX-2 expression was detected by means of immunohistochemistry in a series of 91 breast carcinomas with ductal (n 60) and lobular (n 31) patterns. COX-2 expression was investigated by multivariate analyses and compared with clinicopathological features.Results and conclusions:COX-2 immune positivity and percentage of positive cells correlated significantly with the size, grading, extent of primary tumour and vascular invasion of carcinoma but not with biological parameters (estrogen receptor, progesterone receptor and human EGF receptor 2). The findings of the present study suggest that COX-2 overexpression in lobular and ductal breast cancers, which correlates with traditional clinico-pathological parameters, may be considered as a negative prognostic marker.

We have investigated the influence of the poly(3,4-ethylenedioxythiophene)-blend-poly(styrene-sulfonate) (PEDOT:PSS) layer on the short-circuit current density (J_sc) of single planar heterojunction organic solar cells based on a copper phthalocyanine (CuPc)-buckminsterfullerene (C_60) active layer. Complete optical and electrical modeling of the cell has been performed taking into account optical interferences and exciton diffusion. Comparison of experimental and simulated external quantum efficiency has allowed us to estimate the exciton diffusion length to be 37 nm for the CuPc and 19 nm for the C_60. The dependence of short-circuit current densities versus the thickness of the PEDOT:PSS layer is analyzed and compared with experimental data. It is found that the variation in short-circuit current densities could be explained by optical interferences.

To evaluate in a prospective multicenter trial the feasibility and clinical efficacy of the combination of alemtuzumab (Campath-1H) with the cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) regimen (CHOP-C) as the primary treatment for patients with peripheral T-cell lymphoma (PTCL), between January 2003 and December 2005, 24 consecutive patients with PTCL entered the study and received 8 CHOP courses. Alemtuzumab was added at 30 mg subcutaneously at day −1 initially to the first 4 courses (4 patients), and then to all 8 courses (20 patients). Complete remission (CR) was achieved in 17 (71%) patients, 1 had partial remission, and 6 had stable/progressive disease. At a median follow-up of 16 months (range, 5-42 months), 14 patients were alive, 9 had died from progressive disease, and 1 had died from pneumonia at day +198 while in CR. So far, 13 are disease-free, with an overall median duration of response of 11 months. The most frequent side effects were grade 4 neutropenia and cytomegalovirus (CMV) reactivation. Major infections were Jacob-Creutzfeldt (J-C) virus reactivation, pulmonary invasive aspergillosis, Staphylococcus sepsis, and pneumonia. This study shows that CHOP-C: (1) is a feasible chemoimmunotherapy regimen; (2) is effective in PTCL with a high rate of CR achievement; and (3) is associated with mostly manageable infectious complications. This clinical trial was registered with the Osservatorio Nazionale sulla Sperimentazione cinica as ID no. 141202.

Tidal expiratory flow limitation (FL) is common in patients with acute left heart failure and contributes significantly to orthopnea. Whether tidal FL exists in patients with chronic heart failure (CHF) remains to be determined.

Although it is commonly assumed that pulmonary congestion and edema in patients with chronic heart failure (CHF) promotes peripheral airway closure, closing capacity (CC) has not been measured in CHF patients.

Objective: To assess the potential for stratification of indeterminate cytologic findings on fine-needle aspiration (FNA) of thyroid nodules in an effort to improve therapeutic strategies. Methods: We attempted to determine the malignant risk associated with various indeterminate FNA cytologic patterns by correlation of specimens with the final histologic diagnosis. For this analysis, we identified 294 computerized medical records of surgically treated thyroid nodules during a 5-year period at our institution with the corresponding FNA cytology reports available. Results: Of the 294 surgical cases, 162 with a positive or indeterminate cytologic report were selected, reviewed, and classified. Of 52 patients with positive cytologic findings on FNA, 51 (98%) had a final histologic report of a malignant thyroid nodule. Of 110 patients with indeterminate specimens, 30 (27%) had a final histologic diagnosis of thyroid carcinoma. The presence of nuclear atypia was predictive of thyroid carcinoma in 75% of patients, a Hürthle cell cytologic pattern was associated with a malignant thyroid nodule in 33%, and a hypercellular smear was suggestive of malignant involvement in 26% of cases. The lowest rate of malignant potential was associated with cytologic microfollicular and scant colloid alone subtype (6%). Conclusion: The results of this study show that indeterminate thyroid cytologic specimens can be subdivided into groups with different malignant risks. A microfollicular cytologic pattern in the absence of a hypercellular smear or nuclear atypia does not support a recommendation of surgical treatment. A malignant cytologic diagnosis has a high positive predictive value for detection of thyroid cancer. (Endocr Pract. 2004;10:330-334)

The term poorly differentiated (PD) carcinoma was proposed 20 years ago to define aggressive, follicular-derived thyroid carcinomas with behavior intermediate between follicular/papillary and anaplastic carcinomas. Among the variable histologic patterns recognized in such tumors, trabecular-insular-solid (TIS) areas usually are predominant. Conversely, some authors pointed out that PD carcinomas are characterized by unequivocal, high-grade histology with atypias, high mitotic counts, and necrosis rather than by a specific growth pattern. The clinicopathologic features of a series of 183 thyroid carcinomas with predominant (n = 165 tumors) or focal (n = 18 tumors) TIS growth patterns were studied by univariate and multivariate overall survival analyses and were compared with clinical outcomes. Subgroups included tumors with predominant oxyphilic features (n = 66 tumors) and (residual) papillary carcinoma features (n = 24 tumors). Control groups of papillary (n = 68 tumors), follicular (n = 71 tumors), and anaplastic (n = 35 tumors) carcinomas also were included for overall survival analysis. TIS carcinomas had an intermediate behavior between papillary/follicular and anaplastic carcinomas (P < 0.0001). Univariate and multivariate statistical analyses demonstrated that age > 45 years (P = 0.007), the presence of necrosis (P < 0.0001), and a mitotic count > 3 per 10 high-power fields (P = 0.01) were associated with poor outcome. A simplified scoring system based on statistically significant parameters allowed the identification of three prognostic subgroups (P < 0.0001). PD TIS carcinomas overall followed a more aggressive course compared with differentiated thyroid carcinomas, irrespective of the extent of the TIS component. However, a numeric scoring system applied to specific clinicopathologic parameters further may identify three prognostic categories of patients who have significantly different survival rates at 5 years and 10 years. Cancer 2004;100:950–7. © 2004 American Cancer Society.

The activation of the clotting-fibrinolytic system in cancer patients is common and represents an unfavorable clinical sign. D-dimer (DD) is a sensitive marker of fibrinolysis. The current study comprised 826 new lung carcinoma patients seen consecutively in a single institution over a 10-year period (1992–2001). For each patient, 31 variables, including DD and survival duration, were available for analysis. Only weak relationships between DD and the other variables were found. The DD variable correlated best with the level of lactate dehydrogenase, performance status, tissue polypeptide antigen, stage of disease, and the number of metastases (rho = 0.33, −0.25, 0.18, 0.18, and 0.15, respectively). The D-dimer distinguished patients with different prognoses. The median survival periods were 154 days (95% confidence interval [CI], 122–189 days) and 308 days (95% CI, 227–409 days; log rank statistic, 26.56; P < 0.01), respectively, for abnormally elevated and normal values. The difference was greater in patients with adenocarcinoma and in patients presenting with a less advanced disease, especially in patients with pathologic Stage Ia disease. The best multivariate survival model selected 10 significant covariates, including DD. The authors recommend measuring the plasma level of DD in all new lung carcinoma patients. This measurement may help to formulate individual prognoses and can be used to indicate adjuvant treatment for surgical patients. Cancer 2003;97:3044–52. © 2003 American Cancer Society. DOI 10.1002/cncr.11432

Objective: To describe our experience with fine-needle aspiration biopsy (FNAB) of the thyroid and compare our results with direct palpation versus ultrasound scanning (USS) in an area of endemic goiter in Italy. Methods: We considered all patients submitted to ultrasound-guided FNAB of thyroid nodules during a 10-month period at our outpatient clinic and analyzed the following: (1) clinical data (number of nodules and identification of the nodule for FNAB); (2) USS data (number of nodules and identification of the nodule for FNAB on the basis of hypoechoic pattern + blurred perinodal halo + indicative of blood flow); (3) cytologic specimens, categorized as suspicious, malignant, negative, or nondiagnostic; and (4) histologic final report of the cytologically positive nodules. Results: The study group consisted of 348 female and 72 male patients who underwent FNAB of the thyroid at our institution. Among the 140 patients with no palpable thyroid nodules, USS showed that 106 had a single nodule and 34 had multinodular goiters. Among the 182 patients with a single palpable thyroid nodule, USS revealed that 138 had a single nodule, 42 had a multinodular goiter, and 2 had lobe enlargement without detectable nodules. All 98 patients with multinodular palpable goiter had a similar pattern on USS. Of the 420 cytologic specimens, 46 (11.0%) were positive for thyroid cancer, 313 (74.5%) were negative, and 61 (14.5%) were nondiagnostic. Histologic malignant growth was confirmed in 27 cytologically positive nodules. Of these histologically malignant nodules, 12 (45%) were nonpalpable, 9 (33%) were single palpable nodules, and 6 (22%) were from a nodule with a suspicious ultrasound pattern within a multinodular goiter. Conclusion: Manually guided FNAB is not feasible in nonpalpable nodules and not accurate in a multinodular goiter. Both situations are clinical challenges, and USS should be performed for accurate FNAB under these circumstances. Because 52% of histologically malignant nodules in our study were found only with the aid of ultrasound-guided FNAB, this procedure should be used where multinodular goiter is endemic. Our overall rate of nondiagnostic specimens was comparable to that reported in the literature. (Endocr Pract. 2002;8:282-286)

High-reflectivity dense multilayer coatings were produced for the ultraviolet spectral region. Thin-film single layers and UV mirrors were deposited by ion plating and plasma ion-assisted deposition high- energetic technologies. Optical characterizations of HfO_2 and SiO_2 single layers are made. The optical constants obtained for these two materials are presented. HfO_2 and SiO_2 mirrors with a reflectance of ∼99% near 250 nm are reported.

Working with wavelengths shorter than the deep ultraviolet involves the development of dedicated optics for free-electron lasers with devoted coating techniques and characterizations. High-performance deep-ultraviolet optics are specially developed to create low-loss, high-reflectivity dielectric mirrors with long lifetimes in harsh synchrotron radiation environments. In February 2001, lasing at 189.7 nm, the shortest wavelength obtained so far with free-electron-laser oscillators, was obtained at the European Free-electron-laser project at ELETTRA Synchrotron Light Laboratory, Trieste, Italy. In July 2001, 330-mW extracted power at 250 nm was measured with optimized transmission mirrors. Research and development of coatings correlated to lasing performance are reported.

The redox-sensitive HMGB1 protein is a functional link between oxidative stress and persistent inflammation in muscular dystrophies.

The biology and ethology of Osmia nigrifrons are described and contrasted with O. integra, O. unca, and O. nigrobarbata. The nesting season begins in mid spring and extends about 45 days. Floral records for the species indicate a preference for papilionaceous legumes. Mud nests occur in tubular burrows and in sheltered sites. Nests are composed of from one to several hundred urn-shaped cells. Cells vary between different nest types but possess several constant features: (1) narrowed entry; (2) spiral cell cap structure; (3) constancy of inner dimensions; (4) construction of only soil. Mating, sleeping, cell construction and provisioning behaviour are described.Eggs deposited on top of the pollen-nectar mass required 11·7 days to develop. Larval feeding time averaged 28 days and then the cocoon is spun. Pupation begins in early September and the bee overwinters as adults encased in cocoons.Four years analysis of mortality factors is provided for one population. Mortality rates vary from a low of 31·2% to a high of 59·3%. Four hymenopterous parasites were reared from O. nigrifrons and one, Stelis chlorocyanea, was responsible for from 16% to 43% of the yearly losses.