Annular elastolytic giant cell granuloma treated with topical pimecrolimus.

4openopenErrichetti E; Stinco G; Avellini C; Patrone P.Errichetti, E; Stinco, Giuseppe; Avellini, C; Patrone, Pasqual

Risks of combining immunosuppressive and biological treatments in inflammatory bowel disease - in reply

We thank Roblin and Phelip for their comment on a timely issue. The recent report of the rare hepatosplenic T-cell lymphoma (HSTCL) in young patients with CD treated with both infliximab and azathioprine or steroids has rightly unleashed a series of doubts regarding the optimal use of biological agents in this and other conditions. How these observations may directly relate to the design of our study\u2014as implied by Roblin and Phelip\u2014is unclear though. While azathioprine by itself has been linked to lymphoma development including HSTCL, recent studies have shown that neither infliximab nor methotrexate, which was used in our study, alone or in combination in CD or in rheumatoid arthritis, appear to be associated with an increased risk of developing lymphomas. In addition, methotrexate alone has never been associated thus far with HSTCL in CD

Colloidal CuFeS2 Nanocrystals: Intermediate Fe d-Band Leads to High Photothermal Conversion Efficiency

We describe the colloidal hot-injection synthesis of phase-pure nanocrystals (NCs) of a highly abundant mineral, chalcopyrite (CuFeS2). Absorption bands centered at around 480 and 950 nm, spanning almost the entire visible and near infrared regions, encompass their optical extinction characteristics. These peaks are ascribable to electronic transitions from the valence band (VB) to the empty intermediate band (IB), located in the fundamental gap and mainly composed of Fe 3d orbitals. Laser-irradiation (at 808 nm) of an aqueous suspension of CuFeS2 NCs exhibited significant heating, with a photothermal conversion efficiency of 49%. Such efficient heating is ascribable to the carrier relaxation within the broad IB band (owing to the indirect VB-IB gap), as corroborated by transient absorption measurements. The intense absorption and high photothermal transduction efficiency (PTE) of these NCs in the so-called biological window (650-900 nm) makes them suitable for photothermal therapy as demonstrated by tumor cell annihilation upon laser irradiation. The otherwise harmless nature of these NCs in dark conditions was confirmed by in vitro toxicity tests on two different cell lines. The presence of the deep Fe levels constituting the IB is the origin of such enhanced PTE, which can be used to design other high performing NC photothermal agents.Comment: 12 pages, Chemistry of Materials, 31-May-201

A Review of Dietary Zinc Recommendations

Background. Large discrepancies exist among the dietary zinc recommendations set by expert groups. Objective. To understand the basis for the differences in the dietary zinc recommendations set by the World Health Organization, the U.S. Institute of Medicine, the International Zinc Nutrition Consultative Group, and the European Food Safety Agency. Methods. We compared the sources of the data, the concepts, and methods used by the four expert groups to set the physiological requirements for absorbed zinc, the dietary zinc requirements (termed estimated and/or average requirements), recommended dietary allowances (or recommended nutrient intakes or population reference intakes), and tolerable upper intake levels for selected age, sex, and life-stage groups. Results. All four expert groups used the factorial approach to estimate the physiological requirements for zinc. These are based on the estimates of absorbed zinc required to offset all obligatory zinc losses plus any additional requirements for absorbed zinc for growth, pregnancy, or lactation. However, discrepancies exist in the reference body weights used, studies selected, approaches to estimate endogenous zinc losses, the adjustments applied to derive dietary zinc requirements that take into account zinc bioavailability in the habitual diets, number of dietary zinc recommendations set, and the nomenclature used to describe them. Conclusions. Estimates for the physiological and dietary requirements varied across the four expert groups. The European Food Safety Agency was the only expert group that set dietary zinc recommendations at four different levels of dietary phytate for adults (but not for children) and as yet no tolerable upper intake level for any life-stage group

An animal model for the juvenile non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

11Non Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) are the hepatic manifestations of the metabolic syndrome; worrisome is the booming increase in pediatric age. To recreate the full spectrum of juvenile liver pathology and investigate the gender impact, male and female C57Bl/6 mice were fed with high fat diet plus fructose in the drinking water (HFHC) immediately after weaning (equal to 3-years old human), and disease progression followed for 16 weeks, until adults (equal to 30-years old human). 100% of subjects of both genders on HFHC diet developed steatosis in 4weeks, and some degree of fibrosis in 8weeks, with the 86% of males and 15% of females presenting a stage 2 fibrosis at 16weeks. Despite a similar final liver damage both groups, a sex difference in the pathology progression was observed. Alterations in glucose homeostasis, dyslipidemia, hepatomegaly and obese phenotype were evident from the very beginning in males with an increased hepatic inflammatory activity. Conversely, such alterations were present in females only at the end of the HFHC diet (with the exception of insulin resistance and the hepatic inflammatory state). Interestingly, only females showed an altered hepatic redox state. This juvenile model appears a good platform to unravel the underlying gender dependent mechanisms in the progression from NAFLD to NASH, and to characterize novel therapeutic approaches.openopenMarin, Veronica; Rosso, Natalia; Dal Ben, Matteo; Raseni, Alan; Boschelle, Manuela; Degrassi, Cristina; Nemeckova, Ivana; Nachtigal, Petr; Avellini, Claudio; Tiribelli, Claudio; Gazzin, SilviaMarin, Veronica; Rosso, NATALIA CAROLINA; DAL BEN, Matteo; Raseni, Alan; Boschelle, Manuela; Degrassi, Cristina; Nemeckova, Ivana; Nachtigal, Petr; Avellini, Claudio; Tiribelli, Claudio; Gazzin, Silvi

Transcriptional up-regulation of APE1/Ref-1 in hepatic tumor: Role in hepatocytes resistance to oxidative stress and apoptosis

OBJECTIVE: Human Hepatocellular Carcinoma (HCC) is the fifth most frequent neoplasm worldwide and the most serious complication of long-standing chronic liver diseases (CLD). Its development is associated with chronic inflammation and sustained oxidative stress. Deregulation of apurinic apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1), a master regulator of cellular response to oxidative stress, has been associated with poor prognosis in several cancers including HCC. DESIGN: In the present study we investigated the APE1/Ref-1 mRNA levels in cirrhotic and HCC tissues obtained during HCC resection. The possible protective role of APE1/Ref-1 against oxidative stress and apoptosis was evaluated in vitro in immortalized human hepatocytes (IHH) over-expressing APE1/Ref-1. RESULTS: APE1/Ref-1 was up-regulated in HCC, regulation occurring at the transcriptional level. APE1/Ref-1 mRNA content increased with the progression of liver disease with the transcriptional up-regulation present in cirrhosis significantly increased in HCC. The up-regulation was higher in the less differentiated cancers. In vitro, over-expression of APE1/Ref-1 in normal hepatocytes conferred cell protection against oxidative stress and it was associated with BAX inhibition and escape from apoptosis. CONCLUSION: APE1/Ref-1 is up-regulated in HCC and this over-expression correlates with cancer aggressiveness. The up-regulation occurs at the transcriptional level and it is present in the earliest phases of hepatocarcinogenesis. The APE-1/Ref-1 over-expression is associated with hepatocyte survival and inhibits BAX activation and apoptosis. These data suggest a possible role of APE1/Ref-1 over-expression both in hepatocyte survival and HCC development calling attention to this molecule as a promising marker for HCC diagnosis and treatment

Effects of oral administration of silymarin in a juvenile murine model of non-alcoholic steatohepatitis

The increasing prevalence of non-alcoholic fatty liver disease (NAFLD) in adolescents is challenging the global care system. No therapeutic strategies have been de\ufb01ned so far, and changes in the lifestyle remain the only alternative. In this study, we assessed the protective effects of silymarin in a juvenile non-alcoholic steatohepatitis (NASH) model and the in vitro effects on fat-laden human hepatocytes. C57Bl/6 mice were exposed to HFHC diet immediately after weaning. After eight weeks, animals showed histological signs of NASH. Silymarin was added to the HFHC diet, the treatment continued for additional 12 weeks and the effects on BMI, hepatomegaly, visceral fat, lipid pro\ufb01le, transaminases, HOMA-IR, steatosis, in\ufb02ammation, \ufb01brosis, oxidative stress, and apoptosis were determined. The switch from HFHC to control diet was used to mimic lifestyle changes. In vitro experiments were performed in parallel in human hepatocytes. HFHC diet supplemented with silymarin showed a signi\ufb01cant improvement in glycemia, visceral fat, lipid pro\ufb01le, and liver \ufb01brosis. Moreover, it reduced (both in vitro and in vivo) ALT, hepatic in\ufb02ammation, oxidative stress, and apoptosis. Lifestyle changes restored the control group parameters. The data presented show the bene\ufb01cial effects of the oral administration of silymarin in the absence of changes in the dietary habits in a juvenile model of NASH

Development of a closed-loop BCI based on covert visuospatial attention

openI sistemi moderni di Brain-Computer Interface (BCI) hanno portato un grande progresso tecnologico, rendendo permissivi alcuni compiti, specifici e/o mondani, anche per soggetti affetti da condizioni di disabilità a cui prima risultavano essere complessi o di difficile svolgimento. Una tale tecnologia al momento è applicabile soprattutto nel campo della comunicazione, del controllo di sistemi ausiliari per la disabilità e anche in quello della riabilitazione, in particolare nell’ambito motorio. Principalmente le BCI sviluppate finora si distinguono in due macro-categorie: quelle basate sul rilevamento di potenziali evocati da una stimolazione esterna e quelle basate sul riconoscimento dell’attività cerebrale dovuta all’immaginazione di azioni specifiche. Tuttavia ci sono dei casi in cui queste due metodologie non assicurano un buon grado di controllo agli utenti, in particolare se quest’ultimi presentano sindromi particolari che minano la capacità di attivazione di alcuni tracciati cerebrali. Per questo motivo altri tipi di segnali di controllo sono stati analizzati, uno in particolare è la Covert Visuospatial Attention (CVSA), che consiste in quella comune abilità di focalizzare l’attenzione in un punto del campo visivo senza dover muovere gli occhi. La CVSA risulta essere un buon segnale di controllo poiché non richiede alcuna stimolazione esterna e può essere controllata grazie a una modulazione volontaria dei segnali cerebrali, non dipende dal movimento oculare, e quindi può essere utilizzata anche da utenti che presentano un limitato, o anche nullo, controllo volontario dello sguardo; ed infine essa si basa sull’esecuzione effettiva di un’azione invece che sulla sola immaginazione, cosa che porta beneficio poiché permette di utilizzare un segnale intuitivo e più vicino alla realtà quotidiana. Negli ultimi anni sono stati sviluppati dei paradigmi che utilizzano la CVSA come segnale di input per BCI basate su segnali proveniente da elettroencefalogramma (EEG) con risultati decisamente soddisfacenti, tuttavia raramente sono stati presentati studi che utilizzavano la CVSA come segnale di controllo online per BCI. Questa tesi ha lo scopo di dimostrare che è possibile realizzare una tale BCI ad anello chiuso, ossia un sistema non più basato esclusivamente sulla raccolta di dati e una decodifica a posteriori del risultato, bensì nella quale la CVSA sia utilizzata proprio come segnale di controllo online per un task mentale e l’utente possa ricevere, in tempo reale, un feedback riguardante tale task in base all’evoluzione di tale controllo.Modern Brain-Computer Interface (BCI) systems have brought great technological progress, making certain tasks, specific and/or mundane, permissive even for individuals with disabling conditions to which they were previously found to be complex or difficult to perform. Such technology at present is applicable mainly in the field of communication, control of auxiliary systems for disability, and also in the field of rehabilitation, particularly in the motor field. Mainly the BCIs developed so far are divided into two macro-categories: those based on the detection of potentials evoked by external stimulation and those based on the recognition of brain activity due to the imagination of specific actions. However, there are cases where these two methodologies do not provide a good degree of control to users, particularly if the latter have particular syndromes that undermine the ability to activate certain brain traces. For this reason, other types of control signals have been analyzed, one in particular being Covert Visuospatial Attention (CVSA), which consists of the common ability to focus attention at a point in the visual field without having to move the eyes. CVSA turns out to be a good control signal because it does not require any external stimulation and can be controlled by voluntary modulation of brain signals; it is not dependent on eye movement, and thus can be used even by users with limited, or even no, voluntary gaze control; and finally it is based on the actual execution of an action instead of on imagination alone, which is beneficial because it allows the use of a signal that is intuitive and closer to everyday reality. In recent years, paradigms using CVSA as an input signal for BCI based on signals from electroencephalogram (EEG) have been developed with definitely satisfactory results, however, studies using CVSA as an online control signal for BCI have rarely been presented. This thesis aims to demonstrate that it is possible to realize such a closed-loop BCI, i.e., a system no longer based solely on data collection and an a posteriori decoding of the result, but rather in which CVSA is used precisely as an online control signal for a mental task and the user can receive, in real-time, feedback regarding that task based on the evolution of that control

Il progetto invisibile. Vicinanza come strumento: prove lungo il Tevere

La tesi esplora la relazione tra materialità e immaterialità dello spazio urbano, osservandola tanto nel progetto quanto nelle pratiche quotidiane degli individui. Nella pratica progettuale, infatti, questa relazione è stata perlopiù pensata come dicotomica, attraverso visioni funzionaliste per cui alterare la materialità dello spazio permette di determinarne gli usi possibili. Allo stesso tempo, gli studi urbanistici, antropologici e sociologici delle pratiche urbane hanno mostrato come i modi in cui le persone vivono uno spazio pensano aspetti materiali e immateriali dello spazio come un’unità inscindibile. L’obiettivo della ricerca è quindi quello di costruire uno strumento interpretativo che permetta di ricomprendere all’interno del progetto urbano un’analisi delle pratiche, capace di tenere conto degli sguardi multidisciplinari che si occupano della città. Per raggiungere questo obiettivo mi sono confrontata con il caso del tratto urbano del fiume Tevere, spazio in cui l’opposizione tra una fisicità difficile da alterare e il grande accumularsi di memorie e significati hanno nel tempo reso difficile pensare qualsiasi forma di intervento. Attraverso l’analisi delle stagioni progettuali che hanno ragionato sul Tevere e il confronto con una letteratura multidisciplinare riguardante il rapporto tra materialità e immaterialità, ho definito il concetto di “vicinanza”, termine polisemico che sta ad indicare una lente interpretativa con cui osservare la relazione tra spazio e individui per come viene mediata proprio dalle caratteristiche materiali e immateriali del luogo. Ho messo alla prova questo strumento all’interno di una ricerca sul campo basata sulla teoria attore-rete e su un approccio etnografico. Attraverso l’incontro con i frequentatori di piazza Tevere, lo strumento vicinanza mi ha permesso di individuare e rappresentare graficamente i termini in cui individui e luogo si relazionano e gli effetti di questa relazione. L’unione dell’osservazione sul campo delle pratiche e la conoscenza delle caratteristiche architettoniche di questo spazio permette infatti di individuare gli attanti che fungono da mediatori di queste relazioni, i nodi fondamentali su cui potenzialmente agire, mostrando come nelle pratiche dei frequentatori del Tevere le sue caratteristiche fisiche e immateriali vengano integrate al punto da non poter essere più distinguibili. Lo strumento vicinanza infine emerge per la possibilità che offre nella collaborazione multidisciplinare, facilitando la traducibilità di dati qualitativi all’interno di schemi rappresentativi più vicini e più facilmente utilizzabili in contesti progettuali, andando anzi a permetterci di rappresentare e implementare i progetti invisibili racchiusi nelle pratiche degli individui