Treating Thalassemia Patients with Luspatercept: An Expert Opinion Based on Current Evidence

Luspatercept has recently been approved for the treatment of beta-thalassemia and its use in clinical practice has been increasing. As it is the first erythroid maturation drug available for this diagnosis, the expertise about its use is still limited. To address this point, and to promote awareness and guide the clinical use of luspatercept in beta-thalassemia, this paper was developed as a consensus by experts from the Italian Society of Thalassemia and Hemoglobinopathies (SITE). After a brief presentation of the core features of luspatercept, a comprehensive set of questions is addressed, covering relevant aspects for the practical management of this new therapeutic option

Therapy of age-related exudative macular degeneration with anti-vascular endothelial growth factor drugs: An Italian real life study

Aim: To evaluate the real utilization of ranibizumab and aflibercept in the daily management of patients with neovascular age-related macular degeneration (nAMD) treated at the Eye Clinic of Campania University L.Vanvitelli. Background: Therapy with anti-vascular endothelial growth factor represents the gold standard in wet age-related macular degeneration. There are nonreal life italian studies of this therapy in the literature. Objective: To analyze in our sample the post-therapy variations of best-corrected visual acuity (BCVA) and central retinal thickness (CRT) observed at the end of a 12-month follow-up period. Methods: This real-life study analyzes 109 patients that underwent monthly checks for the first 4 months and then every 2 months until the end of the 12-month follow-up. The sample was first analyzed in its entirety, subsequently subdivided into 3 groups based on baseline BCVA, age, and the number of intravitreal injections performed, in order to identify possible predictive elements of the anti-VEGF response. Results: On average, patients underwent 4.16 ± 1.58 intravitreal anti-VEGF injections in 1 year. At the end of the 12-month follow-up, the patients’ average BCVA increased from 33.01 letters to 33.75 letters (+0.74 ± 9,4 letters), while the average CRT decreased from 346.86 µm to 265.39 µm (-81.47 ± 121 µm). Conclusion: The study shows the efficacy of anti-VEGF therapy in the stabilization of BCVA in nAMD, confirming the differences in visual outcomes compared to clinical trials, mainly for economic-organizational reasons

An aquarium hobbist poisoning: Identification of new palytoxins in Palythoa cf. toxica and complete detoxification of the aquarium water by activated carbon

Palytoxin (PLTX) is a lethal natural toxin often found in Palythoa zoantharians that, together with its congeners, may induce adverse effects in humans after inhalation of toxic aerosols both in open-air and domestic environments, namely in the vicinity of public and private aquaria. In this study, we describe a poisoning of an aquarium hobbyist who was hospitalized after handling a PLTXs-containing zoantharian hexacoral. Furthermore, we provide evidence for water detoxification. The zoantharian was morphologically and genetically identified as Palythoa cf. toxica (Cnidaria: Anthozoa). Palytoxin itself and two new PLTX congeners, a hydroxyPLTX and a deoxyPLTX, were detected and structurally identified by liquid chromatography high resolution multiple stage mass spectrometry (LC-HRMSn, n = 1, 2). Total and individual toxins were quantified by LC-HRMS and sandwich ELISA both in the zoantharian (93.4 and 96.80 \u3bcg/g, respectively) and in the transport water (48.3 and 42.56 \u3bcg/mL, respectively), with an excellent mean bias of 1.3% between the techniques. Activated carbon adsorbed 99.7% of PLTXs contained in the seawater and this represents a good strategy for preventing aquarium hobbyist poisonings

Ovatoxin-a, a palytoxin analogue isolated from Ostreopsis cf. ovata Fukuyo: cytotoxic activity and ELISA detection

This study provides the first evaluation of the cytotoxic effects of the recently identified palytoxin (PLTX) analog, ovatoxin-a (OVTX-a), the major toxin produced by Ostreopsis cf. ovata in the Mediterranean Sea. Its increasing detection during Ostreopsis blooms and in seafood highlights the need to characterize its toxic effects and to set up appropriate detection methods. OVTX-a is about 100 fold less potent than PLTX in reducing HaCaT cells viability (EC50 = 1.1 7 10 129 M vs 1.8 7 10 1211 M, MTT test) in agreement with a reduced binding affinity (Kd = 1.2 7 10 129 vs 2.7 7 10 1211 M, saturation experiments on intact cells). Similarly, OVTX-a hemolytic effect is lower than that of the reference PLTX compound. Ost-D shows the lowest cytotoxicity toward HaCaT keratinocytes, suggesting the lack of a hydroxyl group at C44 as a critical feature for PLTXs cytotoxic effects. A sandwich ELISA developed for PLTX detects also OVTX-a in a sensitive (LOD = 4.2 and LOQ = 5.6 ng/mL) and accurate manner (Bias = 0.3%), also in O. cf. ovata extracts and contaminated mussels. Although in vitro OVTXa appears less toxic than PLTX, its cytotoxicity at nanomolar concentrations after short exposure time rises some concern for human health. The sandwich ELISA can be a viable screening method for OVTXs detection in monitoring program

The sxt Gene and Paralytic Shellfish Poisoning Toxins as Markers for the Monitoring of Toxic Alexandrium Species Blooms

Paralytic shellfish poisoning (PSP) is a serious human illness caused by the ingestion of seafood contaminated with saxitoxin and its derivatives (STXs). These toxins are produced by some species of marine dinoflagellates within the genus Alexandrium. In the Mediterranean Sea, toxic Alexandrium spp. blooms, especially of A. minutum, are frequent and intense with negative impact to coastal ecosystem, aquaculture practices and other economic activities. We conducted a large scale study on the sxt gene and toxin distribution and content in toxic dinoflagellate A. minutum of the Mediterranean Sea using both quantitative PCR (qPCR) and HILIC-HRMS techniques. We developed a new qPCR assay for the estimation of the sxtA1 gene copy number in seawater samples during a bloom event in Syracuse Bay (Mediterranean Sea) with an analytical sensitivity of 2.0 × 10° sxtA1 gene copy number per reaction. The linear correlation between sxtA1 gene copy number and microalgal abundance and between the sxtA1 gene and STX content allowed us to rapidly determine the STX-producing cell concentrations of two Alexandrium species in environmental samples. In these samples, the amount of sxtA1 gene was in the range of 1.38 × 105 − 2.55 × 108 copies/L and the STX concentrations ranged from 41−201 nmol/L. This study described a potential PSP scenario in the Mediterranean Sea.Versión del editor5,228

First Finding of Ostreopsis cf. ovata Toxins in Marine Aerosols

Since the late 1990s, a respiratory syndrome has been repetitively observed in humans concomitant with Ostreopsis spp. blooms (mainly O. cf. ovata) in the Mediterranean area. Previous studies have demonstrated that O. cf. ovata produces analogues of palytoxin (ovatoxins and a putative palytoxin), one of the most potent marine toxins. On the basis of the observed association between O. cf. ovata blooms, respiratory illness in people, and detection of palytoxin complex in algal samples, toxic aerosols, containing Ostreopsis cells and/or the toxins they produce, were postulated to be the cause of human illness. A small scale monitoring study of marine aerosol carried out along the Tuscan coasts (Italy) in 2009 and 2010 is reported. Aerosols were collected concomitantly with O. cf. ovata blooms, and they were analyzed by both PCR assays and LC-HRMS. The results, besides confirming the presence of O. cf. ovata cells, demonstrated for the first time the occurrence of ovatoxins in the aerosol at levels of 2.4 pg of ovatoxins per liter of air. Given the lack of toxicological data on palytoxins by inhalation exposure, our results are only a first step toward a more comprehensiveunderstanding of the Ostreopsis-related respiratory syndrome

Active role of the mucilage in the toxicity mechanism of the harmful benthic dinoflagellate Ostreopsis cf. ovata.

Ostreopsis cf. ovata is a harmful benthic dinoflagellate, widespread along most of the Mediterranean coasts. It produces a wide range of palytoxin-like compounds and variable amounts of mucus that may totally cover substrates, especially during the stationary phase of blooms. Studies on different aspects of the biology and ecology of Ostreopsis spp. are increasing, yet knowledge on toxicity mechanism is still limited. In particular, the potential active role of the mucilaginous matrix has not yet been shown, although when mass mortalities have occurred, organisms have been reported to be covered by the typical brownish mucilage. In order to better elucidate toxicity dependence on direct/indirect contact, the role of the mucilaginous matrix and the potential differences in toxicity along the growth curve of O. cf. ovata, we carried out a toxic bioassay during exponential, stationary and late stationary phases. Simultaneously, a molecular assay was performed to quantify intact cells or to exclude cells presence. A liquid chromatography – high resolution mass spectrometry (LC-HRMS) analysis was also carried out to evaluate toxin profile and content in the different treatments. Our results report higher mortality of model organism, especially during the late stationary phase, when direct contact between a model organism and intact microalgal cells occurs (LC50-48h <4 cells/ml on Artemia salina). Also growth medium devoid of microalgal cells but containing O. cf. ovata mucilage caused significant toxic effects. This finding is also supported by chemical analysis which shows the highest toxin content in pellet extract (95%) and around 5% of toxins in the growth medium holding mucous, while the treatment devoid of both cells and mucilage did not contain any detectable toxins. Additionally, the connection between mucilaginous matrix and thecal plates, pores and trychocysts was explored by way of atomic force microscopy (AFM) to investigate the cell surface at a sub-nanometer resolution, providing a pioneering description of cellular features

POSEIDON: An integrated system for analysis and forecast of hydrological, meteorological and surface marine fields in the Mediterranean area

The Mediterranean area is characterized by relevant hydrological, meteorological and marine processes developing at horizontal space-scales of the order of 1–100 km. In the recent past, several international programs have been addressed (ALPEX, POEM, MAP, etc.)to “resolving” the dynamics of such motions. Other projects (INTERREG-Flooding, MEDEX, etc.)are at present being developed with special emphasis on catastrophic events with major impact on human society that are, quite often, characterized in their manifestation by processes with the above-mentioned scales of motion. In the dynamical evolution of such events, however, equally important is the dynamics of interaction of the local (and sometimes very damaging)pro cesses with others developing at larger scales of motion. In fact, some of the most catastrophic events in the history of Mediterranean countries are associated with dynamical processes covering all the range of space-time scales from planetary to local. The Prevision Operational System for the mEditerranean basIn and the Defence of the lagOon of veNice (POSEIDON)is an integrated system for the analysis and forecast of hydrological, meteorological, oceanic fields specifically designed and set up in order to bridge the gap between global and local scales of motion, by modeling explicitly the above referred to dynamical processes in the range of scales from Mediterranean to local. The core of POSEIDON consists of a “cascade” of numerical models that, starting from global scale numerical analysisforecast, goes all the way to very local phenomena, like tidal propagation in Venice Lagoon. The large computational load imposed by such operational design requires necessarily parallel computing technology: the first model in the cascade is a parallelised version of BOlogna Limited Area Model (BOLAM)running on a Quadrics 128 processors computer (also known as QBOLAM). POSEIDON, developed in the context of a co-operation between the Italian Agency for New technologies, Energy and Environment (Ente per le Nuove tecnologie, l’Energia e l’Ambiente, ENEA)and the Italian Agency for Environmental Protection and Technical Services (Agenzia per la Protezione dell’Ambiente e per i Servizi Tecnici, APAT), has become operational in 2000 and we are presently in the condition of drawing some preliminary conclusions about its performance. In the paper we describe the scientific concepts that were at the basis of the original planning, the structure of the system, its operational cycle and some preliminary scientific and technical evaluations after two years of experimentation