80 research outputs found

    Rapid and innovative instrumental approaches for quality and authenticity of olive oils

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    The quality of virgin olive oils is assessed through the determination of several analytical parameters, whose values must be within the ranges established by the different institutions involved. In addition to official methods, there is a strong need for simple, rapid, and environmentally friendly techniques for the quality control of virgin olive oils and for addressing the challenging task of determining geographical origin and detecting adulterants. Toward this purpose, some of the most interesting applications based on optical spectroscopic techniques, on the measurement of electrical characteristics and on the use of instruments equipped with electronic chemical sensors, including also other promising techniques are herein discussed. These techniques, adequately coupled with an appropriate statistical approach, appear to be promising for assessment of several quality-related parameters. The prediction of sensory attributes and of the oxidative status of virgin olive oils have also been reviewed by adopting these selected techniques, which are also considered to be potentially appropriate solutions for identification of the geographical origin of virgin olive oils and to assess their adulteration with cheaper oils. Overall, the techniques discussed are promising and cutting-edge approaches for the establishment of useful portable instruments for in situ monitoring of the quality of virgin olive oils. Practical applications: The simple, rapid, and environmentally friendly analytical approaches discussed herein represent promising analytical tools for assuring the authenticity and monitoring the quality of virgin olive oils. Such innovative techniques and tools need to be ring-tested and validated. Some innovative reviewed approaches will permit to develop useful portable instruments able to perform in situ appropriate controls also by small laboratories or olive oil mills with limited technical facilities. These equipments will be potentially usable also by trained \u201cnon-professional analytical skilled\u201d people. Some other approaches, rapid but more expensive, will be applicable mainly by quality control labs and will increase the number of samples analyzed per day, thus fostering laboratory proficiency and an effective fighting against olive oil fraud

    Incidence and clinicopathologic features of gastrointestinal stromal tumors. A population-based study.

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    BACKGROUND: Although the diagnostic criteria and pathogenesis of gastrointestinal stromal tumors (GIST) have recently been elucidated, knowledge of the epidemiology of this malignancy is still limited. This study examined the incidence of GIST in the province of Modena, including pathologic features and clinical outcome. METHODS: Gastrointestinal mesenchymal tumors identified by the Modena Cancer Registry between 1991 and 2004 were analyzed with an immunohistochemical panel that included staining for CD-117 and PDGFRalpha. Size, mitotic rate, and other pathologic parameters were recorded. Each tumor was categorized into National Institutes of Health risk categories (very low, low, intermediate, and high risk). RESULTS: One hundred twenty-four cases were classified as GIST. The age-adjusted incidence rate was 6.6 per million. Seventy-five percent of patients were symptomatic; 34% had a previous or concomitant history of cancer. High-risk features were present in 47% of cases. Seventy-eight percent were submitted to radical surgery. After complete resection, the 5-year disease-free survival rates were 94%, 92%, 100%, and 40% for patients at very low, low, intermediate, and high risk, respectively. In multivariate analysis, high risk was the main predictor of recurrence. CONCLUSION: This population-based study shows that the incidence of GIST in Northern Italy is comparable to that reported in other European countries. Survival was favorable in lower risk categories and in most of the resected cases. In our study, resected patients at very low, low, and intermediate risk had a similar outcome. Our data support the need to consider high-risk patients after complete surgical resection for treatment with the best available approach

    Prone Positioning and Intravenous Zanamivir may Represent Effective Alternatives for Patients with Severe ARDS Virus A (H1N1) Related Pneumonia in Hospitals with no Access to ECMO

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    The first patient with influenza A/H1N1-related pneumonia was admitted to an Italian ICU at the end of August 2009. Until then, despite the international alarm, the level of awareness was low and very few Italian hospitals were equipped with ECMOs. Moreover the PCR test for A H1N1 virus was sporadically available and the emergency departments of even the largest institutions could rely only on the rapid test for the urgent screening of patients with pneumonia and respiratory failure. On September 5th, a young and “apparently” previously healthy man, was admitted to our ICU because of a severe ARDS caused by influenza A H1N1 virus. As there was no ECMO available, he was treated with prolonged cycles of prone positioning ventilation. Antiviral treatment was started with Oseltamivir, but as enteral absorption was impaired by paralytic ileus and tube feeding intolerance, Oseltamivir had to be discontinued. Intravenous Zanamivir 1200 mg/day for ten days was therefore prescribed as “off label” antiviral therapy. A bone marrow biopsy allowed the diagnosis of an initial stage of “hairy cells leukaemia.” ARDS related to A/H1N1 influenza was the first sign of the disease in our patient. He did well with complete clearance of the infection from the BAL after 10 days of Zanamivir, although the nasopharyngeal swabs remained positive for ten more days. Prone positioning ventilation may be a life-saver strategy in patients with severe ARDS when ECMO is not immediately available. However, prone positioning ventilation is often associated with severe impairment of the absorption of drugs that require enteral administration via the nasogastric tube. In these cases, intravenous Zanamivir may be an effective alternative strategy

    The Evolving Role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma Treatment

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    Hepatocellular carcinoma (HCC) is one of most common cancers and the fourth leading cause of death worldwide. Commonly, HCC development occurs in a liver that is severely compromised by chronic injury or inflammation. Liver transplantation, hepatic resection, radiofrequency ablation (RFA), transcatheter arterial chemoembolization (TACE), and targeted therapies based on tyrosine protein kinase inhibitors are the most common treatments. The latter group have been used as the primary choice for a decade. However, tumor microenvironment in HCC is strongly immunosuppressive; thus, new treatment approaches for HCC remain necessary. The great expression of immune checkpoint molecules, such as programmed death-1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), lymphocyte activating gene 3 protein (LAG-3), and mucin domain molecule 3 (TIM-3), on tumor and immune cells and the high levels of immunosuppressive cytokines induce T cell inhibition and represent one of the major mechanisms of HCC immune escape. Recently, immunotherapy based on the use of immune checkpoint inhibitors (ICIs), as single agents or in combination with kinase inhibitors, anti-angiogenic drugs, chemotherapeutic agents, and locoregional therapies, offers great promise in the treatment of HCC. This review summarizes the recent clinical studies, as well as ongoing and upcoming trials

    Treatment of Achilles Tendinopathy in Recreational Runners with Peritendinous Hyaluronic Acid Injections: A Viscoelastometric, Functional, and Biochemical Pilot Study

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    Background: Achilles tendinopathy (AT) affects ca. 10 million recreational runners in Europe; the practice of hyaluronic acid (HA) infiltration is being increasingly adopted. The aim of this pilot study was to monitor the effects of a three-local time-spaced injections regimen of HA in the treatment of AT in middle-aged runners combining for the first time viscoelastometric, biochemical, and functional methodologies with routine clinical examinations. Methods: Eight male runners (Age 49.3 ± 3.9), diagnosed for unilateral AT, were given three ultrasound (US) guided peritendinous HA injections at the baseline (T0) and every fifteenth day with a follow-up on the forty-fifth day (T1, T2, and T3). At all-time points patients were assessed for viscoelastic tone and stiffness, maximal voluntary isometric contraction (MVIC), and pain level (Likert scale 0-5). The peritendinous effusions of the injured tendon were collected at T0 and T2 to quantify the volume variations and the IL-1β and MMP-3 levels. Results: At T0 MVIC and pain score were significantly lower and higher, respectively, in injured tendons. The volume, IL-1β and MMP-3 levels decreased in the course of treatment and the clinical endpoints ameliorated over time. Tone, stiffness, and functional performance also varied significantly at T2 and T3, as compared to T0. Conclusions: The sequential peritendinous injections of HA were effective in the amelioration of the clinical symptoms, as well as of the functional and viscoelastic state associated with AT. The determination of the viscoelastometric state may help to precisely evaluate the healing process in AT patients

    STATO DI SALUTE DELLE POPOLAZIONI RESIDENTI NELLE AREE GEOTERMICHE DELLA TOSCANA

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    Objective The limited scientific knowledge on relationship between exposure and health effects in relation to geothermal activity motivated an epidemiologic investigation in Tuscan geothermal area. The study aims to describe the health status of populations living in Tuscany municipalities where concessions for exploitation of geothermal resources were granted. Design This is an ecological study, so it is not useful to produce evidence to sustain a judgment on the cause-effect link. The major limits of this type of study are the use of the residence at municipal level as a proxy of exposure to both environmental and socioeconomic factors and the use of aggregated data of health outcomes that can lead to the well-known ecological fallacy. Setting and participants Sixteen municipalities were included in the study area: eight are part of the so-called "traditional" geothermal area, defined as Northern Geothermal Area (NGA) and eight located in the Amiata Mountain defined as Southern Geothermal Area (SGA). In 2000-2006, the average resident population in the overall area was approximately 43,000 inhabitants. Thirty-one geothermal power plants were active, with a production capacity of 811 MW, 5 of them with 88 MW located in the SGA. Statistical analyses on the entire geothermal area, NGA and SGA subareas, and the sixteen municipalities were performed. Main outcome measures Mortality data were obtained from Tuscany Regional Mortality Registry for the 1971-2006 period, analysing 60 causes of death, of interest for population health status or consistent with "Project SENTIERI" criteria. Hospital discharge records of residents in Tuscany Region in 2004-2006, anywhere admitted to hospital, were analyzed considering only the main diagnosis, excluding repeated admissions for the same cause. The causes taken into account are the same analysed for mortality were considered. Age-standardized mortality rates (TSDM) and the temporal trends of TSDM for four periods (1971-1979, 1980- 1989, 1990-1999, 2000-2006) were computed. Age-standardized mortality/hospitalization ratios (SMR/SHR), with and without adjustment for the deprivation index based on 2001 census data, were calculated: mortality in the years 2000-2006 and hospitalization in 2004-2006. The expected number of events were computed using rates of residents in neighbouring municipalities (municipalities included in 50 km radius circle centred on the study area). Bayesian estimates of mortality/hospitalization ratios (BMR/BHR) at municipal level only and relating maps of the Bayesian risk estimators were elaborated. Congenital malformations (MC) were analysed using data from Tuscan Registry of Birth Defect in 1992-2006 period, relative to outcomes of pregnancies in women resident in the municipalities of study area, wherever the birth or termination of pregnancy occurred. The ratio between observed and expected cases (O/A), with expected defined according to regional rate, were calculated and O/A Bayesian estimates (BMR) are showed only at municipal level . The low weight and the males/females ratio at birth were analysed using data from Tuscany Birth Certificates, covering period 2001-2007, excluding biths occurred in facilities outside Tuscany Region. For Low birth weight (<2,500 grams), very low birth weight (<1,500 grams), low birth weight in women with normal gestational age or greater than 36 weeks, gestational age less than 36 weeks, and the frequency of males, the observed/expected ratio was calculated, with the expected number defined according to regional rate. Results Environmental background High levels of arsenic in drinking water distribution emerges as a critical element, so that several municipalities resorted to granting exemptions for the parameters laid down by the Legislative Decree in force (DLgs 31/01). However, during the final phase of the study, new blast systems activated in the SGA decreased the arsenic levels in the water supply, reaching values not requiring derogations, which, instead, are still effective in some NGA municipalities. Air quality data, from Tuscany Regional Agency for Environmental Protection-ARPAT, show that geothermal activities are able to affect air quality, especially with hydrogen sulphide in NGA, and hydrogen sulphide and mercury in SGA. A significant contribution to the presence of mercury in air is due to previous metallurgical sites. Although mercury levels are belowWHO guideline values, in SGA nearby Siena, values were significantly higher than in other geothermal areas, because of power plant PC2 (turned off in July 2011) in Piancastagnaio municipality. The hydrogen sulphide concentration levels were generally lower than WHO reference values, with occasional excesses over guideline value for health protection (150 &#956;g/m3 as average of the 24 hours). Olfactory pollution was more critic with values exceeding 7-10 &#956;g/m3 range even in areas without geothermal plants.Obiettivo Le limitate conoscenze scientifiche sui rapporti tra esposizione a fattori ambientali correlati all\u27attivit? geotermica e lo stato di salute della popolazione esposta hanno motivato la conduzione di una indagine epidemiologica nell\u27area geotermica toscana basata sull\u27analisi dei dati ambientali e sanitari disponibili negli archivi regionali. Lo studio ha lo scopo di descrivere lo stato di salute delle popolazioni residenti nelle aree geotermiche toscane, identificate con i territori comunali per i quali sono state rilasciate concessioni di sfruttamento della risorsa geotermica. Disegno Lo studio ? di tipo ecologico e quindi non adatto a produrre evidenze che permettano di esprimere un giudizio sul nesso causa-effetto. I maggiori limiti degli studi ecologici derivano dall\u27assunzione che la residenza anagrafica a livello comunale rappresenti una valida misura di esposizione a fattori sia ambientali sia socioeconomici e dall\u27utilizzo di dati aggregati degli esiti sanitari che possono portare a risultati affetti da fallacia ecologica. Setting e partecipanti I comuni inclusi nell\u27area geotermica dello studio sono 16, di cui 8 compresi nell\u27area geotermica cosiddetta ?tradizionale?, che include le localit? di Larderello, Val di Cornia e Radicondoli-Travale (area geotermica Nord) e gli altri 8 situati nella zona dell\u27Amiata senese e grossetana (area geotemica Sud). Nel periodo 2000-2006 la popolazione media residente nell\u27area geotermica complessiva era di oltre 43.000 abitanti. Al momento dello studio erano attive 31 centrali geotermoelettriche con capacit? di produzione di 811 MW, di cui 5 con 88 MW totali nell\u27area geotermica Sud. Le analisi statistiche sono state effettuate a livello di intera area geotermica, delle due subaree geotermiche (Nord e Sud) e dei 16 comuni. Principali misure di outcome La mortalit? ? stata analizzata utilizzando i dati del Registro di mortalit? regionale della Toscana per l\u27intero periodo disponibile (1971-2006), con dettaglio per 60 cause, scelte in quanto di interesse generale per il profilo di salute della popolazione o perch? coerenti con i criteri adottati dal Progetto SENTIERI. L\u27ospedalizzazione ? stata valutata analizzando i dati delle schede di dimissione ospedaliera (SDO) della Re-gione Toscana nel periodo 2004-2006, includendo i ricoverati residenti in Toscana ovunque abbiano effettuato un ricovero, considerando solo la diagnosi principale di ricovero, escludendo i ricoveri ripetuti degli stessi soggetti per la stessa causa. Le cause di ospedalizzazione selezionate per l\u27analisi dei ricoveri sono le stesse utilizzate per l\u27analisi della mortalit?. Per la mortalit? sono stati calcolati i tassi di mortalit? standardizzati per et? (TSDM) e i trend temporali dei TSDM in quattro periodi (1971- 1979, 1980-1989, 1990-1999, 2000-2006). Sia per la mortalit? del periodo 2000-2006, sia per l\u27ospedalizzazione del periodo 2004-2006,sono stati calcolati: &#61692; i rapporti di mortalit?/ospedalizzazione standardizzati per et? (SMR/SHR), con e senza aggiustamento per l\u27indice di deprivazione (ID), utilizzando per il calcolo dell\u27ID i dati del censimento 2001, con gli attesi calcolati usando il tasso di mortalit?/ospedalizzazione della popolazione residente nei comuni limitrofi (comuni con la coordinata geografica del municipio compresa in un cerchio con raggio di 50 km centrato sull\u27area in studio); &#61692; le stime bayesiane dei rapporti di mortalit? (BMR) e di ospedalizzazione (BHR) a livello esclusivamente comunale; &#61692; le mappe (disease mapping) dei rischi bayesiani di mortalit?/ospedalizzazione comunali. Le malformazioni congenite (MC) sono state analizzate utilizzando i dati del Registro toscano dei difetti congeniti (RTDC) nel periodo 1992-2006, relativi a esiti di gravidanze di donne residenti nei comuni dell\u27area in studio, ovunque sia avvenuto il parto o l\u27interruzione di gravidanza. Per le MC ? stato calcolato il rapporto tra casi osservati e casi attesi (O/A), con gli attesi definiti in base al tasso regionale e vengono fornite le stime bayesiane del rapporto O/A (BMR) a livello esclusivamente comunale. Per valutare il basso peso e il rapporto tra maschi e femmine alla nascita sono stati utilizzati i dati dei certificati di assistenza al parto della Regione Toscana, relativi al periodo 2001-2007, con esclusione degli eventi occorsi in presidi di altre regioni. L\u27analisi ? stata condotta considerando i nati con: basso peso alla nascita (LW: peso <2.500 grammi), bassissimo peso alla nascita (VLW: peso <1.500 grammi), basso peso alla nascita nelle donne con et? gestazionale normale e maggiore di 36 settimane (LW36), et? gestazionale inferiore a 36 settimane, e il numero di maschi osservato. Per tutti gli indicatori ? stato calcolato il rapporto osservato/atteso, con l\u27atteso definito in base al tasso regionale. Risultati Il contesto ambientale Dalla descrizione del contesto ambientale, per quanto riguarda l\u27acqua, emerge come elemento di criticit? il riscontro talvolta di elevati livelli di arsenico nelle acque della rete di distribuzione degli acquedotti, tanto che in diverse realt? comunali si ? dovuto far ricorso alla concessione di deroghe ai parametri previsti dal decreto legislativo vigente (DLgs 31/01). Comunque, durante la fase conclusiva dello studio, nell\u27area geotermica Sud i nuovi sistemi abbattitori hanno ridotto i livelli di arsenico nella rete idrica fino a valori tali da non dover pi? ricorrere alle deroghe, ancora attive, invece, in alcuni comuni dell\u27area geotermica Nord. Le informazioni dell\u27ARPAT sui dati dell\u27aria evidenziano che l\u27attivit? geotermica ? in grado di modificare la qualit? dell\u27aria, soprattutto per l\u27acido solfidrico nell\u27area geotermica Nord, e per l\u27acido solfidrico e il mercurio nell\u27area geotermica Sud, in particolare nel versante senese dell\u27Amiata. Per il mercurio nell\u27aria, un contributo rilevante ? legato anche alle emissioni dagli ex siti metallurgici. Sebbene i livelli di mercurio nelle postazioni di monitoraggio rientrino sempre al di sotto dei valori guida raccomandati dall\u27OMS, le concentrazioni riscontrate nell\u27aria dell\u27Amiata senese, e perlopi? legate alla centrale PC2 di Piancastagnaio (spenta nel luglio 2011), sono significativamente superiori a quelle rilevate nelle altre aree geotermiche che, al contrario, sono assestate sugli stessi livelli registrati nei territori non geotermici. I livelli di concentrazione di acido solfidrico sono inferiori ai valori di riferimento, con occasionali superamenti del valore guida di tutela sanitaria OMS (150 &#956;g/m3 come media delle 24 ore). Pi? critici sono i dati di inquinamento olfattivo, che si verifica con il superamento del valore di 7-10 g/m3 di acido solfidrico nell\u27aria, riscontrato con vario grado di intensit? in tutte le postazioni di monitoraggio, anche in aree dove non sono presenti impianti geotermici. In alcune aree con insediamenti produttivi geotermici la frequenza, la persistenza e l\u27intensit? dei cattivi odori sono tali da comportare condizioni di qualit? dell\u27aria scadente

    AI is a viable alternative to high throughput screening: a 318-target study

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    : High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery
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