555 research outputs found
Prospective evaluation of pro/anti-inflammatory cytokines during TKI treatment in chronic myeloid leukemia patients
No full textChronic myeloid leukemia (CML) treatment with tyrosine kinase inhibitors (TKIs) has been associated to an increased risk of Arterial Occlusive Events (AOEs), mainly with nilotinib, but the mechanisms underlying these events have been not clarified yet.
Previously, we confirmed in our retrospective cross-sectional study a higher cardiovascular (CV) risk in nilotinib treated patients, particularly if harboring the unfavorable OLR1 polymorphism and we found a nilotinib-associated pro-inflammatory effect.
We started a multicenter prospective study of tyrosine Kinase Inhibitors induced pro-AtherothROmbotic (KIARO) status in CML patients to furtherly investigate a possible pro-atherothrombotic nilotinib-induced status in a cohort of chronic phase (CP)-CML patients treated with first-line imatinib, nilotinib and dasatinib. In particular, our intents were: to assess any changes in the inflammation status during TKI treatment by measuring pro/anti-inflammatory cytokines (IL-6, IL-10, TNFα and ox-LDL) plasma levels; 2) to record AOEs after applying CV SCORE and evaluate its predictive role; 3) to correlate AOEs with altered inflammation status.
A total of 186 CP-CML patients were enrolled in this study of which 89/186 (48%) were treated with imatinib, 59/186 (32%) with nilotinib and 38/186 (20%) with dasatinib. Results from biochemical analyses performed by enzyme-linked immunosorbent assay (ELISA) test showed higher IL-10 levels at 6 and 12 months in imatinib (p=0.012 and p=0.009, respectively) and dasatinib (p=0.032 and p=0.014, respectively) cohorts compared to nilotinib, while ox-LDL levels increased at 12 months in the nilotinib cohort (p=0.041) in contrast to imatinib and dasatinib. Consequently, IL-6/IL-10 and TNFα/IL-10 ratios were higher in nilotinib cohort compared to imatinib (p=0.042, p=0.044 at 6 months; p=0.040, p=0.041 at 12 months) and dasatinib (p=0.049, p=0.040 at 6 months; p=0.041, p=0.044 at 12 months), suggesting a TKI-driven pro-inflammatory status in nilotinib treated patients. We recorded an AOE only in 5% of patients and, due to the small number of events detected, it was not possible to establish a correlation between AOEs and pro/anti-inflammatory cytokine levels.
Although we applied the SCORE chart in all CML patients enrolled to better identify patients with high risk to experience AOEs, this parameter was not predictive for our cohort. This result may be explained by the strategic choice of TKI at diagnosis, as documented also by the lower median age of the nilotinib treated patients compared to the other two TKI subgroups and by the higher number of traditional CV risk factors in imatinib cohort respect to nilotinib and dasatinib.
Considering that our results showed a pro-inflammatory status in nilotinib subgroup during the first year of treatment and that AOEs occurred after a median treatment duration of 19,1 months, we believe that a further evaluation of pro/anti-inflammatory cytokines at longer treatment follow-up should be performed to better investigate the correlation between pro-atherothrombotic status and AOEs.
In conclusion, we suggest a careful selection of the TKI treatment, according to the presence of baseline CV risk factors and/or previous CV history, in order to offer the best and safe long-term TKI treatment for CML patients, considering as ultimate goal the possibility of reaching a safe TFR and reducing AOEs associated comorbidities
Interazione tra infiammazione, autoimmunità e tumori solidi: approfondimenti sui checkpoint immunitari
No full textInfiammazione, autoimmunità e tumori sono collegati. La deregolazione del sistema immunitario e l'infiammazione sono alla base dell'insorgenza di malattie autoimmuni. Inoltre, l'infiammazione cronica può favorire la progressione dei tumori. Questo progetto di ricerca si proponeva di indagare la relazione tra infiammazione, autoimmunità e tumori solidi in due diverse direzioni: i) esplorare le caratteristiche che contraddistinguono le malattie autoimmuni associate a tumore; ii) indagare gli effetti dell'infiammazione sui checkpoint immunitari nei tumori solidi.
La prima parte del progetto ha riguardato lo studio di biomarcatori sierici in pazienti affetti da dermatomiosite (DM) con e senza tumore, per identificare i pazienti maggiormente a rischio di sviluppare neoplasie. La DM è la malattia autoimmune con la più alta associazione con i tumori. Per caratterizzare i pazienti con DM maggiormente a rischio, abbiamo studiato la presenza di anticorpi diretti contro le proteine di membrana di mioblasti del muscolo scheletrico umani commerciali (HSMM), nel siero di pazienti con DM con e senza tumore. Abbiamo anche analizzato i livelli sierici di checkpoint immunitari solubili, MICA, MICB e PTX3 tra i pazienti con DM con e senza tumore e confrontato i pazienti con DM con i soggetti sani (HC) e i pazienti con artrite reumatoide (RA). Non sono state riscontrate differenze nei biomarcatori analizzati tra i pazienti con e senza tumore. Tuttavia, sono state riscontrate differenze tra pazienti con DM, pazienti con RA e HC. La percentuale di cellule HSMM legate da anticorpi IgG sierici era più alta nei pazienti con DM rispetto agli HC. Inoltre, diverse molecole solubili sono risultate aumentate nei pazienti con DM, suggerendo un potenziale ruolo patogenetico. Le molecole solubili VISTA, CD27 e PTX3 sono risultate i migliori classificatori dei pazienti con DM e i target più promettenti.
La seconda parte del progetto ha riguardato lo studio dell'espressione dei checkpoint immunitari in relazione alle citochine infiammatorie e alla chemioterapia, per fornire indicazioni sui meccanismi patogenetici delle malattie autoimmuni e dei tumori. L'infiammazione promuove lo sviluppo dei tumori, come ad esempio il tumore del colon. Le citochine infiammatorie nel microambiente tumorale e i farmaci utilizzati in terapia possono alterare l'espressione dei checkpoint immunitari. Tuttavia, manca ancora una conoscenza approfondita dei loro effetti. Abbiamo valutato gli effetti di diverse citochine infiammatorie o di farmaci chemioterapici (5-Fluorouracile, Oxaliplatino e Irinotecano) sui livelli dei checkpoint immunitari (PD-L1, PD-L2, GAL9 – inibitori; 4-1BBL, ICOSL – stimolatori; CD155 con duplice funzione) espressi da tre linee cellulari di tumore del colon: HT-29, HCT116 e DLD-1. L'IFNγ aumentava l'espressione di PD-L1 in tutte le linee. Il TNFα aumentava PD-L1 e GAL9 nelle HT-29, aumentava PD-L1 e CD155 e diminuiva 4-1BBL nelle HCT116. PD-L1 aumentava anche con trattamento con IL-1β nelle HT-29 e HCT116 e con IL-6+IL-6Rα solubile nelle DLD-1. PD-L1 è risultato aumentato anche da tutti i farmaci nelle cellule HT-29 e DLD-1, e da 5-Fluorouracile e Irinotecano nelle HCT116. Tutti i farmaci aumentavano leggermente PD-L2 nelle HT-29 e DLD-1 e aumentavano 4-1BBL, CD155 e GAL9 in tutte le linee. L'ICOSL non è risultato espresso né indotto. I dati suggeriscono un aumento dei checkpoint immunitari inibitori e una diminuzione di quelli stimolatori da parte di IFNγ, TNFα, IL-1β e IL-6, che potrebbero influenzare i meccanismi di evasione tumorale o le manifestazioni autoimmuni. I risultati suggeriscono anche un ruolo modulante dei farmaci chemioterapici sul sistema immunitario, che dovrebbe essere preso in considerazione, ad esempio, per pianificare trattamenti combinati.Inflammation, autoimmunity, and cancer are linked. The deregulation of the immune system and inflammation are at the basis of the onset of autoimmune diseases. In addition, chronic inflammation can favor cancer progression. The present research aimed to investigate the relationship between inflammation, autoimmunity, and solid tumors in two different directions: i) exploring the features that characterize cancer-associated autoimmune diseases; ii) investigating the effects of inflammation on immune checkpoint axes in solid tumors.
Part 1 of the project concerned the study of serum biomarkers in patients with dermatomyositis (DM) with and without cancer to identify patients at higher risk of developing cancer. DM is the autoimmune disease with the highest association with cancers. To characterize patients with DM most at risk, we investigated the presence of antibodies directed against plasma membrane proteins of commercial human skeletal muscle myoblasts (HSMM), in the serum of patients with DM with and without cancer. We also analyzed serum levels of soluble immune checkpoints, MICA, MICB, and PTX3 between patients with DM with and without cancer and compared patients with DM to healthy subjects (HC) and patients with rheumatoid arthritis (RA). No differences were found in the investigated biomarkers comparing patients with and without cancer. However, differences were found between patients with DM, patients with RA, and HC. The percentages of HSMMs stained with serum IgG antibodies were higher in DM patients than in HC. In addition, several soluble molecules were increased in patients with DM, suggesting a potential pathogenic role. Soluble VISTA, CD27, and PTX3 resulted in the best classifiers of patients with DM and the most promising targets.
Part 2 of the project concerned the study of immune checkpoint expression in relation to inflammatory cytokines and chemotherapy to provide clues in pathogenic mechanisms in both autoimmune diseases and cancer. Inflammation plays a promoting role in cancer development, e.g. in tumors of the gastrointestinal tract such as colon cancers. Inflammatory cytokines in the tumor microenvironment and drugs used in cancer therapy can alter the expression of immune checkpoints, crucial regulators of the immune system. However, extensive knowledge of their effects is still lacking. We evaluated the effects of different inflammatory cytokines or chemotherapeutic drugs (5-Fluorouracil, Oxaliplatin, and Irinotecan) on immune checkpoint levels expressed by three colon cancer cell lines: HT-29, HCT116, and DLD-1. The following immune checkpoints were investigated: PD-L1, PD-L2, and GAL9 with inhibitory activities; 4-1BBL and ICOSL with stimulatory activities; CD155 with a dual function. Heterogeneity in the responses by the three cell lines tested emerged. IFNγ increased PD-L1 expression in all the cell lines. TNFα increased PD-L1 and GAL9 in HT-29 cells. In addition, TNFα increased PD-L1 and CD155 while it decreased 4-1BBL in HCT116 cells. PD-L1 was also increased by IL-1β in HT-29 and HCT116 and by IL-6+soluble IL-6Rα in DLD-1 cells. Regarding drug treatment, PD-L1 was increased by all the drugs in HT-29 and DLD-1 cells and by 5-Fluorouracil and Irinotecan in HCT116 cells. All the drugs slightly increased PD-L2 on HT-29 and DLD-1 cells and increased 4-1BBL, CD155, and GAL9 expression in the three cell lines. ICOSL was not expressed nor induced. Data suggest an increase in inhibitory immune checkpoints and a decrease of the stimulatory ones by IFNγ, TNFα, IL-1β, and IL-6, which might affect cancer immune escape mechanisms or autoimmune manifestations. Data also suggest a modulating role of chemotherapeutic drugs on the immune system, which should be considered e.g. to plan combined treatments
Rezension zu: Ilaria Bignamini/Clare Hornsby, Digging and Dealing in Eighteenth-Century Rome. With additional research by Irma Della Giovampaola and Jonathan Yarker (New Haven and London 2010)
No full textData of cost-optimal solutions and retrofit design methods for school renovation in a warm climate
No full textAbstract"Efficient Solutions and Cost-Optimal Analysis for Existing School Buildings" (Paolo Maria Congedo, Delia D’Agostino, Cristina Baglivo, Giuliano Tornese, Ilaria Zacà) [1] is the paper that refers to this article. It reports the data related to the establishment of several variants of energy efficient retrofit measures selected for two existing school buildings located in the Mediterranean area. In compliance with the cost-optimal analysis described in the Energy Performance of Buildings Directive and its guidelines (EU, Directive, EU 244,) [2,3], these data are useful for the integration of renewable energy sources and high performance technical systems for school renovation. The data of cost-efficient high performance solutions are provided in tables that are explained within the following sections.The data focus on the describe school refurbishment sector to which European policies and investments are directed. A methodological approach already used in previous studies about new buildings is followed (Baglivo Cristina, Congedo Paolo Maria, D׳Agostino Delia, Zacà Ilaria, 2015; IlariaZacà, Delia D’Agostino, Paolo Maria Congedo, Cristina Baglivo; Baglivo Cristina, Congedo Paolo Maria, D’Agostino Delia, Zacà Ilaria, 2015; Ilaria Zacà, Delia D’Agostino, Paolo Maria Congedo, Cristina Baglivo, 2015; Paolo Maria Congedo, Cristina Baglivo, IlariaZacà, Delia D’Agostino,2015) [4–8]. The files give the cost-optimal solutions for a kindergarten (REF1) and a nursery (REF2) school located in Sanarica and Squinzano (province of Lecce Southern Italy). The two reference buildings differ for construction period, materials and systems.The eleven tables provided contain data about the localization of the buildings, geometrical features and thermal properties of the envelope, as well as the energy efficiency measures related to walls, windows, heating, cooling, dhw and renewables. Output values of energy consumption, gas emission and costs are given for a financial and a macro-economic analysis.This data article provides 288 and 96 combinations for REF1 and REF2, respectively. The output values are obtained using the software ProCasaClima 2015v.2.0
Author Correction: Gluten consumption and inflammation affect the development of celiac disease in at-risk children
No full textThe original version of this Article contained an error in the spelling of the authors Renata Auricchio, Ilaria Calabrese, Martina Galatola, Donatella Cielo, Fortunata Carbone, Marianna Mancuso, Giuseppe Matarese, Riccardo Troncone, Salvatore Auricchio & Luigi Greco which were incorrectly given as Auricchio Renata, Calabrese Ilaria, Galatola Martina, Cielo Donatella, Carbone Fortunata, Mancuso Marianna, Matarese Giuseppe, Troncone Riccardo, Auricchio Salvatore & Greco Luigi. The original article has been corrected
Environmental policies and social impacts. Suggestions from Europeans cities
No full textAre we really sure that green and sustainable are always good for everyone? Ilaria Beretta tries to go beyond the rhetoric of sustainability to understand more deeply the interconnection between economy, society and environment in urban contexts, in the belief that only empirical research and the analysis of data can lead to a correct reading, which is as objective as possible, of the complex reality in which we live. The author, through a comparison between European and U.S. American cities, focuses in particular on policies related to climate change and land use, showing how these, if not properly monitored in their social effects, risk contributing to the tightening of social inequalities, through processes such as ecological and green gentrification. The volume is structured in three parts. In the first section, she illustrates the main European Union’s sustainability and environmental urban policies, focusing on climate change and land use strategies. The second chapter provides a conceptual framework through the environmental justice paradigm, as it applies in Europe and in U.S. Finally, the third chapter offers an empirical analysis of ecological and green gentrification processes, comparing American and European realities, and highlighting how context-specific differences can have profound effects on the manifestation (or not) of these phenomena
El Tlacuache Núm. 458 (2011). 458 Año 11 (2011) marzo. El Tlacuache
No full textReflexiones sobre la migración en la Costa Chica Oaxaqueña Cuando el teléfono suena...por Alejandra A. Ramírez López. -Fronteras Lugares irreales / lugares hiperreales por Ilaria Bologna
Optimization-Based Variable Impedance Control of Robotic Manipulator for Medical Contact Tasks
No full textThis work presents an optimization-based variable impedance control strategy for controlling a robotic manipulator in medical contact tasks. Specifically, the optimal robot stiffness for performing the medical contact task is obtained using online Quadratic programming (QP). In the meantime, an energy tank approach is incorporated into the control loop to regulate the system's passivity. To verify the performance of the proposed strategy, experiments are conducted on both 'static' and 'scanning' medical contact tasks, utilizing materials with different properties, different magnitudes of contact forces, as well as uneven conditions with a human torso phantom model and slope surface. The maximum Root Mean Square Error (RMSE) of force tracking with the proposed method in the 'static' and 'scanning' tasks, across all setups, is 0.88 and 0.5 N, respectively. The experiment results demonstrate the superiority of the proposed control strategy compared with traditional manual contact and constant stiffness (CS) impedance control-based ones. The proposed control framework is promising to be integrated into robot-assisted medical contact tasks, for example, the palpation and Ultrasound (US) imaging scenarios
Werner Sombart and the global society. Anticipations from a classic author of sociology
No full textThe article examines the most salient works in which the sociologist Werner Sombart saw the dimension of globality as a social element, constitutive of mo- dernity and its future. The aim is to understand the role of globality, as an idea and a phenomenon, in the constitution in all aspects of society (economic, political, cultural, anthropological). The Works to which the article refers show a global society, one that goes from the time of Sombart to the present day, as the author had already envisioned in all their potentialities and criticalities
Optimization-Based Variable Impedance Control of Robotic Manipulator for Medical Scanning Task
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