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

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

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

PTH-rP and PTH-R1 Expression in Placentas from Pregnancies Complicated by Gestational Diabetes: New Insights into the Pathophysiology of Hyperglycemia in Pregnancy

Background: this study investigated the expression of parathyroid hormone-related protein (PTH-rP) and PTH/PTH-rP receptor PTH-R1 in placentas from women with gestational DM (GDM), and the relationship between PTH-R1 and PTH-rP expression and pregnancy characteristics. Methods: we prospectively enrolled 78 pregnant women with GDM, and immunochemistry for PTH-rP and PTH-R1 was performed on placentas. Patients were grouped according to the positivity of PTH-R1 or PTH-rP expression, and pregnancy characteristics were compared between the two groups. Results: PTH-rP and PTH-R1 expression were highest in the extravillous cytotrophoblast and in the decidua. In extravillous cytotrophoblast, PTH-rP expression was higher in women with abnormal at fasting glycemia compared to women with abnormal 60' or 120' glycemia (25/25, 50% vs. 6/28, 21.4%, χ2 = 6.12, p = 0.01), and PTH-R1 expression was higher in women with abnormal oral glucose tolerance test (OGTT) at fasting glycemia compared to women with abnormal 60' or 120' glycemia (37/50, 74% vs. 15/28, 53.6%, χ2 = 3.37, p = 0.06). In syncytiotrophoblast, PTH-rP-positive placentas were characterized by higher incidence of 1 min Apgar score &lt; 7 (2/9, 22.2% vs. 2/69, 2.9%, χ2 = 6.11, p = 0.01) and maternal obesity (4/9, 44.4% vs. 11/69, 16.7%, χ2 = 3.81, p = 0.05). Conclusion: placental PTH-rP and PTH-R1 expression is dependent on the type of maternal hyperglycemia, and it is associated with adverse pregnancy outcomes

Diagnosi differenziale dei tumori parotidei: quali caratteristiche di risonanza magnetica considerare?

La finalità del nostro lavoro è di valutare le caratteristiche di risonanza magnetica (RM) tipiche dei tumori parotidei maligni e benigni. Questo studio retrospettivo si basa sulla valutazione di esami RM pre-chirurgici di 94 pazienti con tumori parotidei. I risultati istologici erano disponibili in tutti i casi; abbiamo analizzato 69 lesioni erano benigne (73%) e 25 maligne (27%): 44 adenomi pleomorfi, 18 tumori di Warthin, 7 tumori benigni di diverso istotipo, 6 carcinomi squamocellulari, 3 carcinomi ex-adenomi pleomorfi, 2 carcinomi mucoepidermoidi, 1 tumore adenoidocistico, 13 tumori maligni di diverso istotipo. Sono state valutate le seguenti caratteristiche RM: morfologia, sede, dimensioni, margini, intensità di segnale nelle sequenze T2-pesate e T1-pesate, impregnazione dopo mezzo di contrasto (mdc), intensità di segnale della porzione cistica, presenza o assenza di una capsula, diffusione perineurale, pattern di crescita extraghiandolare e linfoadenopatie laterocervicali. È stata effettuata un’analisi statistica per identificare le caratteristiche RM più indicative di malignità e per definire l’aspetto tipico degli istotipi più comuni. I parametri significativamente predittivi di malignità sono risultati i margini mal-definiti (p < 0,001), le linfoadenopatie (p < 0,001) ed il pattern di crescita infiltrativo (p < 0,001). Le caratteristiche tipiche dell’adenoma pleomorfo sono risultate l’iperintensità di segnale nelle immagini T2-pesate (p = 0,02), l’intensa impregnazione dopo mdc (p < 0,001) ed i margini lobulati (p = 0,04). Le caratteristiche tipiche del tumore di Warthin sono risultate le componenti iperintense nelle immagini T1-pesate (p < 0,001), la localizzazione nel processo parotideo inferiore (p < 0,001) e l’impregnazione post-contrastografica lieve/incompleta (p = 0,01). L’intensità di segnale nelle immagini T1-pesate e T2- pesate e l’impregnazione post-contrastografica si sono rivelate utili nella diagnosi differenziale tra adenoma pleomorfo e tumore di Warthin

Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with b-thalassemia

b-thalassemia is a hereditary disorder with limited approved treatment options; patients experience anemia and its complications, including iron overload. The study aim was to determine whether luspatercept could improve anemia and disease complications in patients with b-thalassemia. This open-label, nonrandomized, uncontrolled study consisted of a 24-week dose-finding and expansion stage (initial stage) and a 5-year extension stage, currently ongoing. Sixty-four patients were enrolled; 33 were non\u2013transfusion dependent (mean hemoglobin, &lt;10.0 g/dL; &lt;4 red blood cell [RBC] units transfused per 8 weeks), and 31 were transfusion dependent (\u20214 RBC units per 8 weeks). Patients received 0.2 to 1.25 mg/kg luspatercept subcutaneously every 21 days for \u20215 cycles (dose-finding stage) and 0.8 to 1.25 mg/kg (expansion cohort and 5-year extension). The primary end point was erythroid response, defined as hemoglobin increase of \u20211.5 g/dL from baseline for \u202114 consecutive days (without RBC transfusions) for non\u2013transfusion-dependent patients or RBC transfusion burden reduction \u202120% over a 12-week period vs the 12 weeks before treatment for transfusion-dependent patients. Eighteen non\u2013transfusion-dependent patients (58%) receiving higher dose levels of luspatercept (0.6-1.25 mg/kg) achieved mean hemoglobin increase \u20211.5 g/dL over \u202114 days vs baseline. Twenty-six (81%) transfusion-dependent patients achieved \u202120% reduction in RBC transfusion burden. The most common grade 1 to 2 adverse events were bone pain, headache, and myalgia. As of the cutoff, 33 patients remain on study. In this study, a high percentage of b-thalassemia patients receiving luspatercept had hemoglobin or transfusion burden improvements. These findings support a randomized clinical trial to assess efficacy and safety. This study was registered at www.clinicaltrials.gov as #NCT01749540 and #NCT02268409

Novel ACTA1 mutation causes late-presenting nemaline myopathy with unusual dark cores

ACTA1 gene encodes the skeletal muscle alpha-actin, the core of thin filaments of the sarcomere. ACTA1 mutations are responsible of several muscle disorders including nemaline, cores, actin aggregate myopathies and fiber-type disproportion. We report clinical, muscle imaging, histopatological and genetic data of an Italian family carrying a novel ACTA1 mutation. All affected members showed a late-presenting, diffuse muscle weakness with sternocleidomastoideus and temporalis atrophy. Mild dysmorphic features were also detected. The most affected muscles by muscle MRI were rectus abdominis, gluteus minimus, vastus intermedius and both gastrocnemii. Muscle biopsy showed the presence of nemaline bodies with several unusual dark areas at Gomori Trichrome, corresponding to unstructured cores with abundant electrodense material by electron microscopy. The molecular analysis revealed missense variant c.148G&gt;A; p.(Gly50Ser) in the exon 3 of ACTA1, segregating with affected members in the family. We performed a functional essay of fibre contractility showing a higher pCa50 (a measure of the calcium sensitivity of force) of type 1 fibers compared to control subjects’ type 1 muscle fibers. Our findings expand the clinico-pathological spectrum of ACTA1-related congenital myopathies and the genetic spectrum of core-rod myopathies