Sindromi drepanocitiche: studio di fattibilità di strategie di prevenzione e rimodellamento della rete assistenziale in un contesto in evoluzione

Sickle cell disease (SCD) is the first genetic disease in the world and remains largely ignored by the population but also by health professionals. SCD is characterized by a variable clinical expression; however most of the patients are at risk to develop acute and severe complications conducting to a fatal issue. Reliable and accurate epidemiological data is a prerequisite for a cost effective prevention program for inherited disorders, which however, is lacking in a number of developing countries. Here we report the first detailed population study in the Piedmont region, north-west Italy, designed to estimate the frequency and distribution of patients with sickle cell disease, annual number of patients newly diagnosed as having SCD, proportion of the patients receiving a regular care in a comprehensive care setting. This study analyzes the adequacy between the services offered for these patients and the real need in this Italian country. OBJECTIVE: The purpose is to estimate the prevalence of sickle cell disease in the Piedmont region and the need for prevention strategies, to evaluate the feasibility of neonatal screening and to propose a realistic healthcare program. METHODS: The estimate of the SCD prevalence changes between January 1978 and December 2011 in the Piedmont region was based on three regional data sources. All consecutive patients with SCD laboratoristic diagnosis were included and specialistic care was offered. For all patients, the demographic and clinical features and the circumstances of SCD diagnosis were described. The next step was to analyse the current prevention and healthcare program in this country and to evaluate the feasibility of a new specific cost effective program and to improve management of sickle cell disease through early parental education and the institution of prophylaxis against infection. RESULTS: According to information obtained from the regional sources, our results indicate that the prevalence of SCD population was 0,022/1000 in 2011 versus 0,008/1000 in 1991; the SCD distribution is heterogeneous in the region. In the next 10 years, the annual incidence was augmented and the changing patterns of immigration, in particular recent African immigration, led to significant numbers of neonates at risk of sickle cell disease (70% of SCD population has not Italian origin or ethnicity). The current healthcare program assures a good survival and quality of life; the prevention program is not complete and neonatal newborn screening is not available but feasible. CONCLUSIONS: Our results are consistent with a changing of the sickle cell disease epidemiology in the Piedmont region with a specific regional distribution; a paucity of high-quality data limits appropriate estimation. The management of SCD requires a dedicated approach; this study support the notion that the healthcare for hemoglobinopathies can benefit from a specific prevention program as neonatal haemoglobinopathies newborn screening despite the logistic problems and economic constraints. The development of prevention as the same time as specific clinical program is pivotal to improving SCD healthcare in this Italian region

Neuroprotective Properties of Cardoon Leaves Extracts against Neurodevelopmental Deficits in an In Vitro Model of Rett Syndrome Depend on the Extraction Method and Harvest Time

This study investigates the bioactive properties of different extracts of cardoon leaves in rescuing neuronal development arrest in an in vitro model of Rett syndrome (RTT). Samples were obtained from plants harvested at different maturity stages and extracted with two different method- ologies, namely Naviglio® and supercritical carbon dioxide (scCO2). While scCO2 extracts more hydrophobic fractions, the Naviglio® method extracts phenolic compounds and less hydrophobic components. Only the scCO2 cardoon leaves extract obtained from plants harvested in spring induced a significant rescue of neuronal atrophy in RTT neurons, while the scCO2 extract from the autumn harvest stimulated dendrite outgrowth in Wild-Type (WT) neurons. The scCO2 extracts were the richest in squalene, 3ß-taraxerol and lupeol, with concentrations in autumn harvest doubling those in spring harvest. The Naviglio® extract was rich in cynaropicrin and exerted a toxic effect at 20 μM on both WT and RTT neurons. When cynaropicrin, squalene, lupeol and 3ß-taraxerol were tested individually, no positive effect was observed, whereas a significant neurotoxicity of cynaropicrin and lupeol was evident. In conclusion, cardoon leaves extracts with high content of hydrophobic bioactive molecules and low cynaropicrin and lupeol concentrations have pharmacological potential to stimulate neuronal development in RTT and WT neurons in vitro

Validity and validation in archetype analysis: practical assessment framework and guidelines

Archetype analysis is a promising approach in sustainability science to identify patterns and explain mechanisms shaping the sustainability of social-ecological systems. Although considerable efforts have been devoted to developing quality standards and methodological advances for archetype analysis, archetype validation remains a major challenge. Drawing on the insights from two international workshops on archetype analysis and on broader literature on validity, we propose a framework that identifies and describes six dimensions of validity: conceptual; construct; internal; external; empirical; and application validity. We first discuss the six dimensions in relation to different methodological approaches and purposes of archetype analysis. We then present an operational use of the framework for researchers to assess the validity of archetype analysis and to support sound archetype identification and policy-relevant applications. Finally, we apply our assessment to 18 published archetype analyses, which we use to describe the challenges and insights in validating the different dimensions and suggest ways to holistically improve the validity of identified archetypes. With this, we contribute to more rigorous archetype analyses, helping to develop the potential of the approach for guiding sustainability solutions.Peer Reviewe

Cereal yield gaps across Europe

peer-reviewedEurope accounts for around 20% of the global cereal production and is a net exporter of ca. 15% of that production. Increasing global demand for cereals justifies questions as to where and by how much Europe’s production can be increased to meet future global market demands, and how much additional nitrogen (N) crops would require. The latter is important as environmental concern and legislation are equally important as production aims in Europe. Here, we used a country-by-country, bottom-up approach to establish statistical estimates of actual grain yield, and compare these to modelled estimates of potential yields for either irrigated or rainfed conditions. In this way, we identified the yield gaps and the opportunities for increased cereal production for wheat, barley and maize, which represent 90% of the cereals grown in Europe. The combined mean annual yield gap of wheat, barley, maize was 239 Mt, or 42% of the yield potential. The national yield gaps ranged between 10 and 70%, with small gaps in many north-western European countries, and large gaps in eastern and south-western Europe. Yield gaps for rainfed and irrigated maize were consistently lower than those of wheat and barley. If the yield gaps of maize, wheat and barley would be reduced from 42% to 20% of potential yields, this would increase annual cereal production by 128 Mt (39%). Potential for higher cereal production exists predominantly in Eastern Europe, and half of Europe’s potential increase is located in Ukraine, Romania and Poland. Unlocking the identified potential for production growth requires a substantial increase of the crop N uptake of 4.8 Mt. Across Europe, the average N uptake gaps, to achieve 80% of the yield potential, were 87, 77 and 43 kg N ha−1 for wheat, barley and maize, respectively. Emphasis on increasing the N use efficiency is necessary to minimize the need for additional N inputs. Whether yield gap reduction is desirable and feasible is a matter of balancing Europe’s role in global food security, farm economic objectives and environmental targets.We received financial contributions from the strategic investment funds (IPOP) of Wageningen University & Research, Bill & Melinda Gates Foundation, MACSUR under EU FACCE-JPI which was funded through several national contributions, and TempAg (http://tempag.net/)

Severe iron overload in Blackfan-Diamond anemia: a case-control study

International audienceABSTRACT. Chronic iron overload is a serious complication in transfusion-dependent patients. Few studies have addressed this issue in Diamond-Blackfan anemia (DBA). We describe a retrospective analysis of iron overload and its related complications in 31 transfusion-dependent Italian DBA patients whose records included one or more evaluation of liver iron concentration (LIC) by means of noninvasive magnetic liver susceptometry with a Superconductive QUantum Interference Device (SQUID). This cohort is also matched with a group of transfusion-dependent β-thalassemia major patients to look for differences. A severe iron overload was observed in 54% patients, especially among those inadequately chelated. The DBA patients displayed a significantly higher LIC than the regularly chelated β-thalassemics. This difference may have been attributable to non-optimal chelation (late onset, type, dose, prescription and compliance), or an unknown biological mechanism that lead to an early severe iron overload. We therefore suggest that all transfusion patients should have an accurate record of their iron intake, and a regular monitoring of iron overload in order to start chelation when a critical transfusion load is reached, and to test the efficacy/compliance of chelation treatment. Physicians taking care of transfusion-dependent DBA patients must be concerned about the frequent and early complications such as cardiac toxicity

Catalytic properties of catechol 1,2-dioxygenase from Acinetobacter radioresistens S13 immobilized on nanosponges

Catechol 1,2-dioxygenases are iron containing enzymes able to convert catechol into cis,cis-muconate, a precursor of the industrially important compound adipic acid. Catechol 1,2-dioxygenase from Acinetobacter radioresistens S13 was immobilized on β-cyclodextrins cross-linked with carbonate groups (nanosponges) with a yield of 29 mg of enzyme per gram of support. This support was chosen for its low cost and its ability to offer different types of interactions with the enzyme. The activity profiles at different pH and temperatures showed a shift of the optimal pH from 8.5, for the free protein, to 9.5, for the immobilized protein and, similarly, a shift in optimal temperature from 30 °C to 50 °C. The Michaelis-Menten constant, KM, increased from 2.0 ± 0.3 μM, for the free form, to 16.6 ± 4.8 μM for the immobilized enzyme, whereas the rate constant, kcat, values were found to be 32 ± 2 s−1 and 27 ± 3 s−1 for the free and immobilized forms respectively. The immobilization process also increased the thermostability of the enzyme with 60% residual activity after 90 min at 40 °C for the immobilized proteinversus 20% for the free enzyme. A residual activity of 75% was found after 15 min at 60 °C for the immobilized enzyme while the free form showed a total loss of activity under the same conditions. The activity toward other substrates, such as 3- and 4-methylcatechol and 4-chlorocatechol, was retained by the immobilized enzyme. A small scale bioreactor was constructed and was able to convert catechol into cis,cis-muconic acid with high efficiency for 70 day