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Graphical abstract, Being considered minor vexations, fungal infections hinder the life of about 15% of the world population superficially, with rare threats to life in case of invasive sepsis. A significant rise in the intrusive mycoses due to machiavellian fungal species is observed over the years due to increased pathology and fatality in people battling life-threatening diseases. Individuals undergoing therapy with immune suppressive drugs plus recovering from viral infections have shown to develop fungal sepsis as secondary infections while recovering or after. Currently, the whole world is fighting against the fright of Coronavirus disease (COVID-19), and corticosteroids being the primitive therapeutic to combat the COVID-19 inflammation, leads to an immune-compromised state, thereby allowing the not so harmful fungi to violate the immune barrier and flourish in the host. A wide range of fungal co-infection is observed in the survivors and patients of COVID-19. Fungal species of Candida, Aspergillus and Mucorales, are burdening the lives of COVID-19 patients/survivors in the form of Yellow/Green, White and Black fungus. This is the first article of its kind to assemble note on fungal infections seen in the current human health scenario till date and provides a strong message to the clinicians, researchers and physicians around the world “non-pathological fungus should not be dismissed as contaminants, they can quell immunocompromised hosts”.

The co-existence of humans and gut microbiota started millions of years ago. Until now, a balance gradually developed between gut bacteria and their hosts. It is now recognized that gut microbiota are key to form adequate immune and metabolic functions and, more in general, for the maintenance of good health. Gut microbiota are established before birth under the influence of maternal nutrition and metabolic status, which can impact the future metabolic risk of the offspring in terms of obesity, diabetes, and cardiometabolic disorders during the lifespan. Obesity and diabetes are prone to disrupt the gut microbiota and alter the gut barrier permeability, leading to metabolic endotoxaemia with its detrimental consequences on health. Specific bacterial sequences are now viewed as peculiar signatures of the metabolic syndrome across life stages in each individual, and are linked to pathogenesis of cardiovascular diseases (CVDs) via metabolic products (metabolites) and immune modulation. These mechanisms have been linked, in association with abnormalities in microbial richness and diversity, to an increased risk of developing arterial hypertension, systemic inflammation, nonalcoholic fatty liver disease, coronary artery disease, chronic kidney disease, and heart failure. Emerging strategies for the manipulation of intestinal microbiota represent a promising therapeutic option for the prevention and treatment of CVD especially in individuals prone to CV events.

Data analysis on the pathogenesis and risk factors of neonatal thrombosis was carried out. The main risk factor of any neonatal thrombosis is central catheter installment, but other maternal, fetal and neonatal factors should be taken into consideration. We discuss the epidemiology of neonatal thrombosis and the main features of the hemostasis system in newborns, the most significant risk factors, including genetic and acquired thrombophilia. We consider the von Willebrand factor activity and ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) level in the development of neonatal thrombotic microangiopathy. Finally, we discuss the basic principles of prevented neonatal thrombosis by using low molecular weight heparins.

Sea fennel (Crithmum maritimum L.) contains several bioactive compounds like vitamin C, polyphenols, essential oils, and fatty acids. The present study was aimed at exploring the lactic acid fermentation of sea fennel sprouts by the selection and inoculation of multiple strain starters to produce laboratory-scale prototypes and, subsequently, a pilot-scale prototype. A rapid pH reduction was seen in the laboratory-scale prototypes, mainly due to lactic acid production. Linoleic and α-linolenic acids were the most abundant detected fatty acids, while among volatile compounds monoterpene hydrocarbons prevailed. Fruity, pungent and yogurt notes emerged from the sensory analysis. The analysis of the pilot-scale prototype confirmed the physico-chemical data collected from the laboratory scale prototypes, except for a slower acidification. In addition, a decrease in antioxidant activity and content of vitamin C, fiber and total polyphenols was seen during fermentation, whereas sensory analysis revealed a kerosene-like note, a salty flavor, and a crunchy consistency. No coagulase positive staphylococci and botulinum toxin-producing clostridia were detected. The results overall collected highlighted the great potential of sea fennel and selected lactic acid bacteria starters to produce high value, safe and microbiologically stable preserves.

Highly populated coastal environments receive large quantities of treated and untreated wastewater from human and industrial sources. Bivalve molluscs accumulate and retain contaminants, and their analysis provides evidence of past contamination. Rivers and precipitation are major routes of bacteriological pollution from surface or sub-surface runoff flowing into coastal areas. However, relationships between runoff, precipitation, and bacterial contamination are site-specific and dependent on the physiographical characteristics of each catchment. In this work, we evaluated the influence of precipitation and river discharge on molluscs' Escherichia coli concentrations at three sites in Central Italy, aiming at quantifying how hydrometeorological conditions affect bacteriological contamination of selected bivalve production areas. Rank-order correlation analysis indicated a stronger association between E. coli concentrations and the modelled Pescara River discharge maxima (r = 0.69) than between E. coli concentration and rainfall maxima (r = 0.35). Discharge peaks from the Pescara River caused an increase in E. coli concentration in bivalves in 87% of cases, provided that the runoff peak occurred 1–6 days prior to the sampling date. Precipitation in coastal area was linked to almost 60% of cases of E. coli high concentrations and may enhance bacterial transportation offshore, when associated with a larger-scale weather system, which causes overflow occurrence. HIGHLIGHTS Using a grid-distributed hydrological model to assess hydrometeorological conditions in the absence of direct measurements.; Analysis of a previous uninvestigated area.; New discharge threshold determining Escherichia coli concentration peaks found in Central Italy in order to allow the development of an early warning system for risk assessment.

Background: Elevation of plasma free fatty acids as a principal aspect of type 2 diabetes maintains etiologically insulin insensitivity in target cells. TNF-α inhibitory effects on key insulin signaling pathway elements remain to be verified in insulinresistant hepatic cells. Thus, TNF-α knockdown effects on the key elements of insulin signaling were investigated in the palmitate-induced insulin-resistant hepatocytes. The Akt serine kinase, a key protein of the insulin signaling pathway, phosphorylation was monitored to understand the TNF-α effect on probable enhancing of insulin resistance. Methods: Insulin-resistant HepG2 cells were produced using 0.5 mM palmitate treatment and shRNA-mediated TNF-α gene knockdown and its down-regulation confirmed using ELISA technique. Western blotting analysis was used to assess the Akt protein phosphorylation status. Results: Palmitate-induced insulin resistance caused TNF-α protein overexpression 1.2-, 2.78, and 2.25- fold as compared to the control cells at post-treatment times of 8 h, 16 h, and 24 h, respectively. In the presence of palmitate, TNF-α expression showed around 30% reduction in TNF-α knockdown cells as compared to normal cells. In the TNF-α down-regulated cell, Akt phosphorylation was approximately 62% more than control cells after treatment with 100 nM insulin in conjugation with 0.5 mM palmitate. Conclusions: The obtained data demonstrated that TNF-α protein expression reduction improved insulin-stimulated Akt phosphorylation in the HepG2 cells and decreased lipidinduced insulin resistance of the diabetic hepatocytes.

Mt. Etna, in Sicily (Italy), produces effusive and explosive eruptions from summit craters and flanks. Petrology of erupted products has proved fundamental to explore the relationship between magma dynamics within the plumbing system and eruptive styles. Data of Sr Nd isotopes are quite scarce if compared with the great number of chemical analyses carried out in products of last decades. We measure Sr Nd isotopes, major and trace elements in products emitted from 2001 to 2012, and consider also published analyses of the 1995–2001 eruptions, because carried out in the same laboratories of 2001–2012 ones. Furthermore, we take into account other published analyses extending back to the 14th century, even if performed by different facilities. Based on this dataset, magma dynamics operating at different timescales inside the volcano's plumbing system have been explored. Our analyses evidence that, from 2001–2012, three magma types are present in the volcano's plumbing system: (i) a deep and poorly evolved basaltic and K-trachybasaltic magma, enriched in radiogenic Sr and LILE, erupted during the 2001 and 2002–03 flank activity; (ii) a shallower more evolved K-trachybasaltic magma, less enriched in radiogenic Sr, feeding both summit and flank eruptions and (iii) an uncommon, and scarcely radiogenic hawaiitic magma, LILE poor, emitted exclusively from a small sector of the 2002–03 eruptive fissures. By considering a broader time scale, from 14th to 21st century, we conclude that: (i) different magmatic components are present in the deep volcano's plumbing system, at about 10–12 km b.s.l; (ii) a decoupling of geochemical and isotopic features in magmas stored at different depths is observed after the 1974 flank eruption up to date; (iii) mixing between different magmas is an efficient magmatic process to produce magma differentiation at Mt. Etna, regardless of the investigated temporal scale.

Cucullanus carettae Baylis, 1923 (Nematoda: Cucullanidae) is found worldwide in loggerhead turtles (Caretta caretta). Regarding the Mediterranean, C. carettae has been identified in the Tyrrhenian and the Ionian Sea and a unique description of a Cucullanus sp. specimen in loggerheads from the Adriatic Sea has been reported in the literature so far. In the framework of a bio-monitoring project of the Abruzzo and Molise coasts, a parasitological survey was performed on stranded and by-caught sea turtles, at the Istituto Zooprofilattico of Abruzzo and Molise “G. Caporale.” During necropsy, the gastrointestinal system of 72 stranded loggerhead turtles was analyzed for the presence of endoparasites and fecal samples were collected for coprological examination. Adult C. carettae (n = 123) was found in the upper intestine of one loggerhead turtle, associated with chronic lymphoplasmocytic enteritis. Additionally, five stool samples (6.9%) were positive for Cucullanus sp. eggs. Molecular characterization of adult nematodes was carried out to study phylogenetic relationships among the Cucullanus species. To our knowledge, this is the first morphological and molecular identification of C. carettae in loggerhead turtles from the Adriatic Sea. Additional studies on the distribution of this parasite in the Mediterranean are encouraged.

The use of malolactic starter cultures, often offer no guarantee of microbiological success due to the chemical and physical factors (pH, ethanol, SO2, nutrient availability) that occur during the winemaking process. This study was born with the aim of improving the performance of the lactic acid bacteria used as a starter culture in the de-acidification of wines. Two commercial strains of Oenococcus oeni, were used. Was evaluated the effect of exogenous l-proline added during the bacterial growth, on the improvement of their survival in the presence of different ethanol concentrations and their ability to degrade l-malic acid in synthetic wine with the presence of 12% (v/v) and 13% (v/v) of ethanol. The results showed that l-proline improve ethanol tolerance and so the malolactic performances of O. oeni. This work represents an important strategy to ensure good vitality and improve the performance of the malolactic starter.

Background: Obesity is now recognized as a worldwide health issue and has reached epidemic proportions, affecting both developed and developing countries. The World Obesity Federation stated that “Obesity is a chronic relapsing disease process”: as a result, obesity has been recognized internationally as a chronic disease. : The primary cause of the metabolic syndrome and increase of the cardiovascular risk have been identified in "sick fat", a condition then defined as adiposopathy. Heart attacks, strokes and renal failures are pathologies that have mid-risk factors such as dyslipidemia, hypertension and diabetes, which in turn are caused by obesity, whose primary risk factor is represented by the diet. The aim of the present review is to consider the importance of body composition, together with chronic inflammation and a new gut microbiota data that may turn out to be crucial elements of some target treatment of human obesity. Methods: In this review, we performed research using PubMed database reviewing the evidence in the literature of evidence information regarding the link between obesity and body composition in the development of metabolic disease via inflammation markers and in particular, the new role exerted by gut microbiota. Results: Several papers were evaluated searching for differences in fat mass and disease risk. We also identified the same papers dealing with differences in body composition and metabolic syndrome. Our attention focuses also on a new frontier of gut microbiota composition in the body weight decrease and anti-inflammatory effects. Conclusion: To the saving of lean mass, for the prevention of cardiometabolic diseases, also considering the relationship with obesity, it is necessary to reduce the inflammatory state, acting on the gut-microbiota and on the intestinal permeability. To improve the health of the intestinal flora, we propose a 4P medicine and treatment with probiotics, prebiotics, postbiotics, and polyphenols.

In industrial winery, the use of mixed starter cultures composed of Saccharomyces and non-Saccharomyces yeasts is an approach of growing importance for winemakers to enhance the sensory and complexity of the wine without compromising the quality. In this work, the oenological properties and enzymatic activities of 196 non-Saccharomyces yeasts, belonging to Hanseniaspora guilliermondii and Hanseniaspora uvarum species, were investigated. This screening has allowed the selection of the best non-Saccharomyces yeast strain and the use of vinification for white grape of Campania Vitis vinifera cv Fiano, in an industrial scale. The experimental fermentations were performed in four different batches: batch A (H. guilliermondii BF1 and S. cerevisiae 404 in sequential inoculum); batch B only inoculum of S. cerevisiae 404; batch C without inoculation (spontaneous fermentation); batch D with the inoculum of H. guilliermondii BF1 strain. The results of chemical and sensorial analyses have showed that the best wine comes from batch A. In conclusion, the use of H. guilliermondii BF1 with good oenological properties and a strong β-glucosidase activity allowed to improve the sensorial complexity of the wine. Selected non-Saccharomyces yeast could be applied profitably to winemaking to enhance the quality of the wine using new fermentation technologies, and could be used in industrial winery.

The aim of this study was to evaluate the dynamics of proteolysis during dough fermentation started with different lactic acid bacteria species, through the identification of intermediate and small-sized peptides generated during fermentation. Single-strain cultures of Levilactobacillus brevis, Fructilactobacillus sanfranciscensis, Companilactobacillus alimentarius, and Leuconostoc pseudomesenteroides were assayed as sourdough starters. Assays were carried out at lab-scale for 48 h of fermentation, using both unstarted and yeast-leavened dough as controls. Physicochemical and microbiological analyses were combined with peptidomic and proteomic profiling, identifying several hundreds of peptides mainly released from the water-soluble wheat proteins, including β-amylase, triticin, and serpins. Both α- and γ-gliadins were hydrolyzed, though only at the N-terminal domain, while the central protein region – encrypting celiac disease epitopes– remained unaffected. The bacterial-mediated consumption of sugars and the concomitant hydrolysis of starch degrading β-amylase could underlie improved digestibility and several nutritionally beneficial effects of sourdough baked products.

Nuclear envelope (NE) is a Ca2+-storing organelle controlling neuronal differentiation through nuclear Ca2+ concentrations ([Ca2+]n). However, how [Ca2+]n regulates this important function remains unknown. Here, we investigated the role of the nuclear form of the Na+/Ca2+ exchanger 1(nuNCX1) during the different stages of neuronal differentiation and the involvement of PTEN/PI3’K/Akt pathway. In neuronal cells, nuNCX1 was detected on the inner membrane of the NE where protein expression and activity of the exchanger increased during NGF-induced differentiation. nuNCX1 activation by Na+-free perfusion induced a time-dependent activation of nuclear-resident PI3K/Akt pathway in isolated nuclei. To discriminate the contribution of nuNCX1 from those of plasma membrane NCX, we generated a chimeric protein composed of the fluorophore EYFP, the exchanger inhibitory peptide, and the nuclear localization signal, named XIP-NLS. Fura-2 measurements on single nuclei and patch-clamp experiments in whole-cell configuration showed that XIP-NLS selectively inhibited nuNCX1. Once it reached the nuclear compartment, XIP-NLS increased the nucleoplasmic Ca2+ peak elicited by ATP and reduced Akt phosphorylation, GAP-43 and MAP-2 expression through nuclear-resident PTEN induction. Furthermore, in accordance with the prevention of the neuronal phenotype, XIP-NLS significantly reduced TTX-sensitive Na+ currents and membrane potential during neuronal differentiation. The selective inhibition of nuNCX1 by XIP-NLS increased the percentage of β III tubulin-positive immature neurons in mature cultures of MAP-2-positive cortical neurons, thus unraveling a new function for nuNCX1 in regulating neuronal differentiation through [Ca2+]n-dependent PTEN/PI3K/Akt pathway.

Copper (Cu)-transporting P1B-type ATPases are ubiquitous metal transporters and crucial for maintaining Cu homeostasis in all domains of life. In bacteria, the P1B-type ATPase CopA is required for Cu-detoxification and exports excess Cu(I) in an ATP-dependent reaction from the cytosol into the periplasm. CopA is a member of the CopA1-type ATPase family and has been biochemically and structurally characterized in detail. In contrast, less is known about members of the CopA2-type ATPase family, which are predicted to transport Cu(I) into the periplasm for cuproprotein maturation. One example is CcoI, which is required for the maturation of cbb3-type cytochrome oxidase (cbb3-Cox) in different species. Here, we reconstituted purified CcoI of Rhodobacter capsulatus into liposomes and determined Cu transport using solid-supported membrane electrophysiology. The data demonstrate ATP-dependent Cu(I) translocation by CcoI, while no transport is observed in the presence of a non-hydrolysable ATP analog. CcoI contains two cytosolically exposed N-terminal metal binding sites (N-MBSs), which are both important, but not essential for Cu delivery to cbb3-Cox. CcoI and cbb3-Cox activity assays in the presence of different Cu concentrations suggest that the glutaredoxin-like N-MBS1 is primarily involved in regulating the ATPase activity of CcoI, while the CopZ-like N-MBS2 is involved in Cu(I) acquisition. The interaction of CcoI with periplasmic Cu chaperones was analyzed by genetically fusing CcoI to the chaperone SenC. The CcoI-SenC fusion protein was fully functional in vivo and sufficient to provide Cu for cbb3-Cox maturation. In summary, our data demonstrate that CcoI provides the link between the cytosolic and periplasmic Cu chaperone networks during cbb3-Cox assembly.

The use of natural compounds as food preservatives is becoming increasingly popular as it is perceived positively by consumers. Among these substances, essential oils have attracted great interest owing to their antioxidant and antimicrobial properties. However, several challenges impair the use of essential oils in food products, such as their degradation or loss during food processing and storage, the strong aroma, even at low concentrations, which may negatively affect the sensory characteristics of food. In this context, the development of nanoformulations able to stabilize essential oils may represent a smart solution to this issue. The aim of the study was to evaluate the efficiency of alginate-based nanoformulations enriched with lemongrass (Cymbopogon nardus) essential oil (LEO) and Tween 80 against several fungi namely Penicillium expansus, Aspergillus niger and Rhizopus spp. Firstly, the flow behavior of systems at different concentrations of alginate (1%, 2% and 3% w/w) were studied. Then, emulsion-based nanoformulations at different concentrations of lemongrass essential oil in the range of 0–2% w/w were stabilized by a fixed amount of Tween 80, characterized and tested for their antifungal activity. Our results showed that the best nanoformulation able to inhibit Rhizopus spp., Penicillium expansum and Aspergillus niger, for at least 10 days, was constituted by 1% alginate/1.5% LEO/1% Tween 80. Hence, the incorporation of essential oil into nanoformulation systems may represent a valid alternative to overcome the disadvantages that limit the commercial application of essential oils.

Background After primary maternal cytomegalovirus (CMV) infection during pregnancy, infants are at risk for disease. Methods Factors predictive of infant outcome were analyzed in a database of 304 pregnant women with primary infection. These women were enrolled between 2010 and 2017 and delivered 281 infants, of whom 108 were CMV infected. Long term follow-up occurred for 173 uninfected and 106 infected infants at age 4 years (range, 1–8 years). One hundred fifty-seven women were treated with an average of 2 doses (range, 1–6 doses) of high-dose hyperimmune globulin (HIG: 200 mg/kg/infusion). We used a regression model to define predictors of fetal infection, symptoms at birth, and long-term sequelae; 31 covariates were tested. Results Four factors predicted fetal infection: a 1.8-fold increase (30% vs 56%) in the rate of congenital infection without HIG (adjusted odds ratio [AOR], 5.2; P < .0001), a 1.8-fold increase (32% vs 56%) associated with maternal viral DNAemia prior to HIG administration (AOR, 3.0; P = .002), abnormal ultrasounds (AOR, 59; P = .0002), and diagnosis of maternal infection by seroconversion rather than avidity (AOR, 3.3; P = .007). Lack of HIG and abnormal ultrasounds also predicted symptoms (P = .001). Long-term sequelae were predicted by not receiving HIG (AOR, 13.2; P = .001), maternal infection in early gestation (odds ratio [OR], 0.9; P = .017), and abnormal ultrasounds (OR, 7.6; P < .003). Prevalence and copy/number of DNAemia declined after HIG. Conclusions Maternal viremia predicts fetal infection and neonatal outcome. This may help patient counseling. High-dose HIG may prevent fetal infection and disease and is associated with the resolution of DNAemia.

CIMMYT maize inbred lines (CMLs) are freely distributed to breeding programs around the world. Better information on phenotypic and genotypic diversity may provide guidance to breeders on how to use more efficiently the CMLs in their breeding programs. In this study a group of 291 CIMMYT maize inbred lines, was phenotyped by nine agro-morphological traits in south Córdoba, Argentina and genotyped using 18,082 SNPs. Based on the geographic information and the environmental adaptation, 291 CMLs were classified into eight subgroups. Anthesis-silking interval (IAE) was the trait with higher phenotypic diversity. A 40% of maize inbred lines, with IAE less than five days, show a good adaptation to growing conditions in south Córdoba, Argentina. The low phenotypic variation explained by environmental adaptation subgroups indicates that population structure is only a minor factor contributing to phenotypic diversity in this panel. Principal component analysis (ACP) allowed us to obtain phenotypic and genotypic orderings. Generalized procrustes analysis (APG) indicated a 60% consensus between both data type from the total panel of maize lines. In each environmental adaptation subgroup, the APG consensus was higher. This result, which might indicate linkage disequilibrium between SNPs markers and the genes controlling these agro-morphological traits, is promising and could be used as an initial tool in the identification of Quantitative Trait Loci (QTL). Information on genetic diversity, population structure and phenotypic diversity in local environments will help maize breeders to better understand how to use the current CIMMYT maize inbred lines group. Key words: broad-sense heritability, multivariate analysis, SNPs, agro-morphological traits.

Biological early warning systems (BEWS) are installed worldwide for the continuous control of water intended for multiple uses. Sentinel aquatic organisms can alert us to contaminant presence through their physiological or behavioural alterations. The present study is aimed at sharing the experience acquired with water biomonitoring of the Gran Sasso-Sirente (GS-S) aquifer. It represents the major source of the Abruzzi region surface water, also intended as drinkable and for irrigation use. Besides the biomonitoring of drinkable water of the Teramo Province made by Daphnia Toximeter and irrigation water of the L’Aquila Province by Algae Toximeter, a novel sensor named “SmartShell” has been developed to register the behaviour of the “pea clam” P. casertanum, an autochthonous small bivalve living in the Nature 2000 site “Tirino River spring”. The valve movements have been recorded directly on the field. Its behavioural rhythms have been analysed through spectral analyses, providing the basis for further investigations on their alterations as early warnings and allowing us to propose this autochthonous bivalve species as a novel sentinel organism for spring water.

Introduction: The quantitative determination of urinary Cystatin C (cyst-C) associated with the qualitative analysis of its polymorphisms is an excellent method for early identification of newborns predisposed to renal function impairment. PETIA, PENIA and EIA are the immunometric methods used for the quantitative determination of cyst-C inhuman biologic fluid but they have limitations and do not allow qualitative analysis. The present study is a validation of Immunoblot SDS-PAGE for the qualitative and quantitative analysis of urinary cyst-C. Methods: Urine was collected from neonates in the nursey at S. Maria della Misericordia Hospital. Urinary cyst-C was investigated by the immunoblot SDS-PAGE and by reading of optical density. Results: The qualitative analysis showed two different molecular forms: A reactivity at about 70 KDa in all samples and a reactivity at 13 KDa in a limited number of samples. This analysis allows the correlation of the polymorphisms of cyst-C with specific alterations of renal function in newborns. The quantitative analysis is specific, sensitive and accurate. In fact the coefficient of variation for assay precision was 10% and for assay accuracy was ± 10%, the detection limit was 0.009 ng/ µL and the calibration line has satisfactory linearity (range 0.02-0.3 ng/µL). The stability of urinary cyst-C was acceptable, even without the use of protease inhibitors, as long as the assay was performed on freshly recruited urine or immediately after thawing the samples, which had been stored for up to six months. Conclusion: Immunoblot SDS-PAGE analysis is a valid method of obtaining a qualitative and quantitative analysis of urinary cyst-C. This method presents unique information about a previously unknown 70 KDa cyst-C form. The assay may offer potential diagnostic information not available with immunometric method.

Introduction: Trimethylamine N-oxide (TMAO) may play a key mediator role in the relationship between the diet, gut microbiota and cardiovascular diseases, particularly in people with kidney failure. The aim of this review is to evaluate which foods have a greater influence on blood or urinary trimethylamine N-oxide (TMAO) levels. Methods: 391 language articles were screened, and 27 were analysed and summarized for this review, using the keywords “TMAO” AND “egg” OR “meat” OR “fish” OR “dairy” OR “vegetables” OR “fruit” OR “food” in December 2020. Results: A strong correlation between TMAO and fish consumption, mainly saltwater fish and shellfish, but not freshwater fish, has been demonstrated. Associations of the consumption of eggs, dairy and meat with TMAO are less clear and may depend on other factors such as microbiota or cooking methods. Plant-based foods do not seem to influence TMAO but have been less investigated. Discussion: Consumption of saltwater fish, dark meat fish and shellfish seems to be associated with an increase in urine or plasma TMAO values. Further studies are needed to understand the relationship between increased risk of cardiovascular disease and plasma levels of TMAO due to fish consumption. Interventions coupled with long-term dietary patterns targeting the gut microbiota seem promising.

Loggerhead sea turtle (C. caretta) is the official European bioindicator of marine litter in the Mediterranean Sea. In 2019, 8 sea turtles, out of 28 specimens loggerhead on the Adriatic coast of Molise, were subjected to necropsy. The intestinal contents were collected and the microplastics until 0.45 μm were extracted. Qualitative and quantitative assessments were performed by stereomicroscope observation and spectroscopic analyses (attenuated total reflection-Fourier transform infrared spectroscopy, ATR-FTIR and Raman microspectroscopy, RMS). Moreover, the analytical quantification of polyethylene terephthalate (PET), polycarbonate (PC), para phthalic acid (PTA) and bisphenol A (BPA) in fat and liver tissues was performed by LC-MS/MS. Microparticles ranging from 0.45 μm to 1 mm were found in all turtles, for a total of 623, while plastic litter greater than 1 mm were found only in 4 specimens (ranging from 0.03 to 0.11 g). Nineteen different polymers and 10 pigments, including polyester (100% of animals), high-density polyethylene (50%) and polypropylene (50%) were identified. BPA, PTA and PET were detected in fat and liver tissues of all animals, while PC was found only in 50%. A major prevalence was registered in the abdominal fat tissue, although only PC compounds were significantly higher in abdominal tissue (p p Graphical abstract

In this work was evaluated the effect of sequential inoculum of Hanseniaspora uvarum AS27 strain and a commercial Saccharomyces cerevisiae yeast on the physical–chemical and organoleptic features of Aglianico, a traditional red wine of Southern Italy. Four fermentation treatments on a pilot scale were performed. In fermentation treatment A, the alcoholic fermentation was spontaneously conducted by the indigenous yeasts present in grape must. In the fermentation treatments B and C were inoculated respectively S. cerevisiae FE and H. uvarum AS27 strains, as a single starter. The fermentation treatment D was initially inoculated with H. uvarum AS27, and S. cerevisiae strain was added after 72 h (sequential inoculation). Microbiological, physical–chemical parameters and sensory profiles of the wines have been defined. The results showed that the use of H. uvarum AS27, in sequential inoculum with S. cerevisiae FE, influenced the wine composition, enriching it in polyphenolic and volatile compounds. Further, the sensory evaluation showed that the use of H. uvarum AS27 strain, in co-culture with S. cerevisiae, gives the wine more pleasant characteristics. Therefore, the results have highlighted how the use of particular non-Saccharomyces yeasts can represent a biotechnological resource in red wine production.

International audience; Numerous studies have proven a close relationship between inflammatory diseases and the state of hypercoagulability. In fact, thromboembolic complications represent one of the main causes of disability and mortality in acute and chronic inflammatory diseases, cancer and obstetric complications. Despite this, the processes of hemostasis and immune responses have long been considered separately; currently, work is underway to identify the molecular basis for a relationship between such systems. It has been identified that various pro-inflammatory stimuli are capable of triggering a coagulation cascade, which in turn modulates inflammatory responses. Neutrophil extracellular traps (NETs) are the networks of histones of extracellular DNA generated by neutrophils in response to inflammatory stimuli. The hemostasis is activated against infection in order to minimize the spread of infection and, if possible, inactivate the infectious agent. Another molecular network is based on fibrin. Over the last 10 years, there has been accumulated a whole body of evidence that NETs and fibrin are able to form a united network within a thrombus, stabilizing each other. Similarities and molecular cross-reactions are also present in the processes of fibrinolysis and lysis of NETs. Both NETs and von Willebrand factor (vWF) are involved in thrombosis as well as inflammation. During the development of these conditions, a series of events occurs in the microvascular network, including endothelial activation, NETs formation, vWF secretion, adhesion, aggregation, and activation of blood cells. The activity of vWF multimers is regulated by the specific metalloproteinase ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). Studies have shown that interactions between NETs and vWF can lead to arterial and venous thrombosis and inflammation. In addition, the contents released from activated neutrophils or NETs result in decreased ADAMTS-13 activity, which can occur in both thrombotic microangiopathies and acute ischemic stroke. Recently, NETs have been envisioned as a cause of endothelial damage and immunothrombosis in COVID-19. In addition, vWF and ADAMTS-13 levels predict COVID-19 mortality. In this review, we summarize the biological characteristics and interactions of NETs, vWF, and ADAMTS-13, the effect of NETs on hemostasis regulation and discuss their role in thrombotic conditions, sepsis, COVID-19, and obstetric complications.

The Mediterranean monk seal (Monachus monachus) is the rarest species of pinniped in the world. Necropsy of a Mediterranean monk seal pup that stranded alive on the southern Adriatic Italian coast and died a few hours later revealed co-infection by cetacean morbillivirus (CeMV) and Toxoplasma gondii. Pathological lesions included a multifocal, moderate to severe, necrotizing myocarditis and a diffuse, chronic, moderate interstitial pneumonia with bronchial and bronchiolar epithelial hyperplasia. Lesions of atypical necrotizing arteritis were seen in the aorta and major pulmonary arteries in association with the presence T. gondii organisms. Severe haemorrhagic foci and lesions of non-suppurative meningoencephalitis, together with the presence of protozoal cysts, were seen in the brain. Co-infection of CeMV and T. gondii has not been previously reported in monk seals. The vascular lesions found in this animal can be considered atypical because they have not been reported in other terrestrial or marine mammal species. The disseminated toxoplasmosis associated with the unusual vascular and haemorrhagic brain lesions could be related to the immunosuppressive effects of CeMV infection.

In the present study, a 4-year surveillance plan for the detection of lipophilic marine biotoxins in Mytilus galloprovincialis and Callista chione from different aquaculture farms and natural beds along the Central Adriatic coasts of Croatia was reported. The samples were analyzed by a validated LC-MS/MS method in accordance with the Regulation (EU) No 2019/627. Lipophilic marine biotoxins belonging to the okadaic acid group, except for azaspiracids, as well as yessotoxins were found at different concentrations, always below the maximum limits established by the Regulation (EC) No 853/2004. The seasonal distribution showed the highest values in summer months, and an interannual variability was also observed, probably due to environmental conditions aging on the density of harmful algal blooms. The comprehensive data reported in this study should help the future research in making advancing prediction models along the Eastern Adriatic coast.

Iron chelation therapy (ICT) has become a mainstay in heavily transfused hematological patients, with the aim to reduce iron overload (IOL) and prevent organ damage. This therapeutic approach is already widely used in thalassemic patients and in low-risk Myelodysplastic Syndrome (MDS) patients. More recently, ICT has been proposed for high-risk MDS, especially when an allogeneic bone marrow transplantation has been planned. Furthermore, other hematological and hereditary disorders, characterized by considerable transfusion support to manage anemia, could benefit from this therapy. Meanwhile, data accumulated on how iron toxicity could exacerbate anemia and other clinical comorbidities due to oxidative stress radical oxygen species (ROS) mediated by free iron species. Taking all into consideration, together with the availability of approved oral iron chelators, we envision a larger use of ICT in the near future. The aim of this review is to better identify those non-thalassemic patients who can benefit from ICT and give practical tips for management of this therapeutic strategy.

Adverse outcome pathway (AOP) is a conceptual framework that links a molecular initiating event (MIE) via intermediate key events (KEs) with adverse effects (adverse outcomes, AO) relevant for risk assessment, through defined KE relationships (KERs). The aim of the present work is to describe a linear AOP, supported by experimental data, for skeletal craniofacial defects as the AO. This AO was selected in view of its relative high incidence in humans and the suspected relation to chemical exposure. We focused on inhibition of CYP26, a retinoic acid (RA) metabolizing enzyme, as MIE, based on robust previously published data. Conazoles were selected as representative stressors. Intermediate KEs are RA disbalance, aberrant HOX gene expression, disrupted specification, migration, and differentiation of neural crest cells, and branchial arch dysmorphology. We described the biological basis of the postulated events and conducted weight of evidence (WoE) assessments. The biological plausibility and the overall empirical evidence were assessed as high and moderate, respectively, the latter taking into consideration the moderate evidence for concordance of dose-response and temporal relationships. Finally, the essentiality assessment of the KEs, considered as high, supported the robustness of the presented AOP. This AOP, which appears of relevance to humans, thus contributes to mechanistic underpinning of selected test methods, thereby supporting their application in integrated new approach test methodologies and strategies and application in a regulatory context.

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation. Funding The European Commission FP7 NeurOmics project; CHDI Foundation; the Medical Research Council UK; the Brain Research Trust; and the Guarantors of Brain.

Astrocyte dysfunction emerges early in Alzheimer's disease (AD) and may contribute to its pathology and progression. Recently, the voltage gated potassium channel KV3.4 subunit, which underlies the fast-inactivating K(+) currents, has been recognized to be relevant for AD pathogenesis and is emerging as a new target candidate for AD. In the present study, we investigated both in in vitro and in vivo models of AD the expression and functional activity of KV3.4 potassium channel subunits in astrocytes. In primary astrocytes our biochemical, immunohistochemical, and electrophysiological studies demonstrated a time-dependent upregulation of KV3.4 expression and functional activity after exposure to amyloid-β (Aβ) oligomers. Consistently, astrocytic KV3.4 expression was upregulated in the cerebral cortex, hippocampus, and cerebellum of 6-month-old Tg2576 mice. Further, confocal triple labeling studies revealed that in 6-month-old Tg2576 mice, KV3.4 was intensely coexpressed with Aβ in nonplaque associated astrocytes. Interestingly, in the cortical and hippocampal regions of 12-month-old Tg2576 mice, plaque-associated astrocytes much more intensely expressed KV3.4 subunits, but not Aβ. More important, we evidenced that the selective knockdown of KV3.4 expression significantly downregulated both glial fibrillary acidic protein levels and Aβ trimers in the brain of 6-month-old Tg2576 mice. Collectively, our results demonstrate that the expression and function of KV3.4 channel subunits are precociously upregulated in cultured astrocytes exposed to Aβ oligomers and in reactive astrocytes of AD Tg2576 mice.

Amyotrophic lateral sclerosis (ALS) is a severe human adult-onset neurodegenerative disease affecting lower and upper motor neurons. In >20% of cases, the familial form of ALS is caused by mutations in the gene encoding Cu,Zn-superoxide dismutase (SOD1). Interestingly, administration of wild-type SOD1 to SOD1(G93A) transgenic rats ameliorates motor symptoms through an unknown mechanism. Here we investigated whether the neuroprotective effects of SOD1 are due to the Ca(2+)-dependent activation of such prosurvival signaling pathway and not to its catalytic activity. To this aim, we also examined the mechanism of neuroprotective action of ApoSOD1, the metal-depleted state of SOD1 that lacks dismutase activity, in differentiated motor neuron-like NSC-34 cells and in primary motor neurons exposed to the cycad neurotoxin beta-methylamino-L-alanine (L-BMAA). Preincubation of ApoSOD1 and SOD1, but not of human recombinant SOD1(G93A), prevented cell death in motor neurons exposed to L-BMAA. Moreover, ApoSOD1 elicited ERK1/2 and Akt phosphorylation in motor neurons through an early increase of intracellular Ca(2+) concentration ([Ca(2+)]i). Accordingly, inhibition of ERK1/2 by siMEK1 and PD98059 counteracted ApoSOD1- and SOD1-induced neuroprotection. Similarly, transfection of the dominant-negative form of Akt in NSC-34 motor neurons and treatment with the selective PI3K inhibitor LY294002 prevented ApoSOD1- and SOD1-mediated neuroprotective effects in L-BMAA-treated motor neurons. Furthermore, ApoSOD1 and SOD1 prevented the expression of the two markers of L-BMAA-induced ER stress GRP78 and caspase-12. Collectively, our data indicate that ApoSOD1, which is devoid of any catalytic dismutase activity, exerts a neuroprotective effect through an early activation of Ca(2+)/Akt/ERK1/2 pro-survival pathway that, in turn, prevents ER stress in a neurotoxic model of ALS.

An unprecedented exploding demand for broadband high-speed, heterogeneous, ultra-reliable, secure, and low latency communications is motivating and leading the definition of new standards and technologies for wireless communications, known as 5G. The massive scientific and industrial interest in 5G communications is motivated by the key role that 5G systems can play in the worldwide economic and societal processes to support next generation vertical services, e.g., Internet of Things, Industry 4.0, automotive and transportation sectors, e-Health, factories of the future, etc. The integration of satellite and terrestrial networks can be a cornerstone to the realisation of the foreseen heterogeneous global system. Due to their inherent large footprint, satellites can efficiently complement and extend dense terrestrial networks, both in densely populated areas and in rural zones, as well as provide reliable Mission Critical services. While in the past terrestrial and satellite networks have evolved almost independently from each other, leading to a difficult a posteriori integration, the definition of the future 5G paradigm provides the unique chance for a fully-fledged architecture. This Special Issue aims at collecting the latest progresses in scientific, industrial, regulatory, and standardisation analyses, as well as sharing novel concepts and ideas, for a fully integrated satellite-terrestrial network. Potential topics include, but are not limited to: • System architecture: challenges and solutions • Impact of satellite channel impairments on the system physical layer • Integration with low altitude drones • Scheduling • Higher layers design • Regulatory aspects • Standards evolution • Coexistence with Advanced LTE and IoT networks • Application to 5G verticals • Cognitive radio techniques

This study identified the lactic acid bacteria (LAB) biota and the volatilome profile of 28 typical sourdoughs of Irpinia—a large area of the Campania region of Southern Italy where numerous breads are produced, even today, following the ancient procedures of sourdough fermentation and for which information on the microbiological and sensory profile is lacking in literature. For this purpose, microbial quality, LAB biodiversity, chemical, and technological characteristics, as well as aroma profile by solid-phase microextraction technique (SPME)–gas chromatography/mass spectrometry (GC/MS) of Irpinian sourdoughs were investigated. The dominant LAB microbiota was examined by both culture-dependent and culture-independent methods Polymerase Chain Reaction/Denaturing Gradient Gel Electrophoresis (PCR-DGGE). Results showed a high biodiversity in LAB community whereas the most frequent lactobacilli species recognized were Lactobacillus plantarum (ca. 22% of total LAB isolates), Lactobacillus sanfranciscensis (11%), Lactobacillus paralimentarius (8%), and Lactobacillus rossiae (6.5%), whereas LAB cocci could be mainly referred to Pediococcus pentosaceus (9.5% of total LAB isolates), Leuconostoc spp. (7.8%), and Weissella cibaria (7.7%). Sourdoughs were characterized by the dominance of one or two LAB species, thus proving that the environment influences the selection and the establishment of few key LAB species and that no specific correlation can be traced between microbial composition and geographical origin of the samples. Furthermore, although sourdoughs were characterized by different qualitative and quantitative volatile organic compound (VOC) compositions, no noticeable correlation between volatilome profile and geographical origin was found. However, it emerged that for more isolated locations, it was possible to find the existence of microbial biotypes and sensory profiles with a strong identity, thus revealing the existence of highly traditional and evocative bread recipes in those geographical contexts.

In humans, mutation of glycine 93 to alanine of Cu++/Zn++ superoxide dismutase type-1 (SOD1-G93 A) has been associated to some familial cases of Amyotrophic Lateral Sclerosis (ALS). Several evidence proposed the involvement of environmental pollutants that like mercury could accelerate ALS symptoms. SH-SY5Y cells stably transfected with SOD1 and G93 A mutant of SOD1 constructs were exposed to non-toxic concentrations (0.01 μM) of ethylmercury thiosalicylate (thimerosal) for 24 h. Interestingly, we found that thimerosal, in SOD1-G93 A cells, but not in SOD1 cells, reduced cell survival. Furthermore, thimerosal-induced cell death occurred in a concentration dependent-manner and was prevented by the Sirtuin 1 (SIRT1) activator Resveratrol (RSV). Moreover, thimerosal decreased the protein expression of transcription factor Downstream Regulatory Element Antagonist Modulator (DREAM), but not DREAM gene. Interestingly, DREAM reduction was blocked by co-treatment with RSV, suggesting the participation of SIRT1 in determining this effect. Immunoprecipitation experiments in SOD1-G93 A cells exposed to thimerosal demonstrated that RSV increased DREAM deacetylation and reduced its polyubiquitination. In addition, RSV counteracted thimerosal-enhanced prodynorphin (PDYN) mRNA, a DREAM target gene. Furthermore, cortical neurons transiently transfected with SOD1-G93 A construct and exposed to thimerosal (0.5 μM/24 h) showed a reduction of DREAM and an up-regulation of the prodynorphin gene. Importantly, both the treatment with RSV or the transfection of siRNA against prodynorphin significantly reduced thimerosal-induced neurotoxicity, while DREAM knocking-down potentiated thimerosal-reduced cell survival. These results demonstrate the particular vulnerability of SOD1-G93 A neuronal cells to thimerosal and that RSV via SIRT1 counteracts the neurodetrimental effect of this toxicant by preventing DREAM reduction and prodynorphin up-regulation.

On December 12, 2019 a new coronavirus (SARS-CoV-2) emerged in Wuhan, China, triggering a pandemic of severe acute respiratory syndrome in humans (COVID-19). Today, the scientific community is investing all the resources available to find any therapy and prevention strategies to defeat COVID-19. In this context, immunonutrition can play a pivotal role in improving immune responses against viral infections. Immunonutrition has been based on the concept that malnutrition impairs immune function. Therefore, immunonutrition involves feeding enriched with various pharmaconutrients (Omega 3 Fatty Acids, Vitamin C, Arginine, Glutamine, Selenium, Zinc, Vitamin, E and Vitamin D) to modulate inflammatory responses, acquired immune response and to improve patient outcomes. In literature, significant evidences indicate that obesity, a malnutrition state, negatively impacts on immune system functionality and on host defense, impairing protection from infections. Immunonutrients can promote patient recovery by inhibiting inflammatory responses and regulating immune function. Immune system dysfunction is considered to increase the risk of viral infections, such as SARS-CoV-2, and was observed in different pathological situations. Obese patients develop severe COVID-19 sequelae, due to the high concentrations of TNF-α, MCP-1 and IL-6 produced in the meantime by visceral and subcutaneous adipose tissue and by innate immunity. Moreover, leptin, released by adipose tissue, helps to increase inflammatory milieu with a dysregulation of the immune response. Additionally, gut microbiota plays a crucial role in the maturation, development and functions of both innate and adaptive immune system, as well as contributing to develop obese phenotype. The gut microbiota has been shown to affect lung health through a vital crosstalk between gut microbiota and lungs, called the “gut-lung axis”. This axis communicates through a bi-directional pathway in which endotoxins, or microbial metabolites, may affect the lung through the blood and when inflammation occurs in the lung, this in turn can affect the gut microbiota. Therefore, the modulation of gut microbiota in obese COVID-19 patients can play a key role in immunonutrition therapeutic strategy. This umbrella review seeks to answer the question of whether a nutritional approach can be used to enhance the immune system’s response to obesity in obese patients affected by COVID-19.

Nerve Growth Factor (NGF) and Brain Derived Neurotrophic Factor (BDNF) are crucial for the peripheral and central nervous system development, respectively, and differential brain and blood levels in Intra Uterine Growth Restriction (IUGR) and prematurity have been found. As reduced growth of brain regions, measured at 30-40 days of postnatal period, has been demonstrated in preterm and IUGR neonates who showed impaired neuro-development at two years of age, in this study, the levels of NGF and BDNF were evaluated in the urine samples of 30-40 day-old subjects who were full-term, preterm and IUGR and showed a normal or an abnormal neuro-development at follow up after two years. Neurotrophins were measured concurrently with volumes of whole brain, thalamus, frontal cortex and cerebellum. Values were then correlated with later neuro-developmental outcome. Biochemical parameters and cerebral volumes were assessed using colorimetric ELISA kits and three-dimensional ultra-sonography (3DUS), respectively. Neuro-development was estimated using the Griffiths-II test. Urinary NGF and brain volumes significantly correlated and were lower in preterm and IUGR subjects characterized by poor neuro-development. No differences were seen in the case of BDNF. The present investigation demonstrates, for the first time, the strong and direct association of NGF with brain growth at the initial phase of the postnatal period and with neuro-developmental outcome in later life. Remarkably, urinary NGF may be suggested as an early prognostic indicator of high long-term risk of motor and cognitive impairment in IUGR and preterm neonates.

Background and Aims Worldwide, amatoxin-containing mushrooms account for >95% of mushroom poisoning-related death. Recently, Amanita species not containing amatoxin, such as Amanita Proxima, have been implicated in poisonings resulting in acute kidney injury. Allenic norleucine has been isolated from these fungi and accounts for their nephrotoxicity. AKI is characterized by interstitial nephritis on renal biopsy and resolves over weeks. Here we report several case of AKI associated with cardiac involvement. We aimed to describe improvement of cardiac output and resolution of AKI after replacement dialysis treatment. Method From January 2013 to January 2020, eight consecutive patients with AKI from Amanita Proxima poisoning were enrolled in a large Italian community hospital. We collected clinical data including hepatic, cardiac and renal function parameters. In all the cases studied, in addition to renal failure, there were a worsening of cardiac function. Results We identified 8 patients suffering from Amanita Proxima intoxication, with a mean age of 57.8±24.5 years (62.5% were female). All patients presented preliminary gastrointestinal symptoms occurred within 24 hours from the mushroom intake and suddenly developed kidney injury and underwent replacement dialysis treatment using standard bicarbonate dialysis. At baseline, patients' mean eGFR was 7±2.3 mL/min/1.73m, with a mean BUN of 124±41 mg/dl, AST 52,6±42,5 IU/L, ALT 115,5±105,7 IU/L,. Cardiac involvement was also found in all cases, evidenced by ECG alteration (62,5%), an increase in myocardial necrosis enzymes (87,5%) and a reduction in the ejection fraction (50%) of about 15 percent. In 25% of cases, typical chest pain was also found. Mean troponin was 3,82±7,31 ng/ml, myoglobin 243,55±275,18 ng/ml CPK 187,6±42 IU/L and CK-MB of 13,72±14,96 IU/L. Kidney failure and cardiac impairment was successfully resolved in 87.5% of poisonings. At the end of treatment all renal and cardiac parameters significantly decreased (P Only one patient died for intoxication-related complication. The mean number of dialysis treatments to achieve the resolution of renal failure was eight. Conclusions The cases reported suggest that Amanita proxima have a potential severe cardiac toxicity that request a precise cardiac evaluation. Early identification of intoxication and rapid start of dialysis therapy are crucial for the resolution of heart damage.

Per request of MD, Dr Sci Med, Professor, Academician of RAS Nikolay N. Volodin, President of Russian association of specialists in perinatal medicine (RASPM) one of leading specialists in obstetrics, gynecology and perinatal medicine in the world prof. Gian Carlo Di Renzo have prepared the Expert Report on the Elina Sushkevich case. Taken into account the importance of this case for healthcare professionals, we publish the full text in the original and translated into Russian.

The quality of ready meals is affected by several factors that may impair stability and nutritional value. In this work, we evaluated the overall quality of four traditional meals (Basilicata region) prepared according to the cook&amp, chill method, packaged in air or modified atmosphere packaging (MAP, 70% N2 and 30% CO2), and stored at 4 °C for seven days. The shelf-life was determined by Listeria monocytogenes challenge testing and inactivation by microwave (MW) heating was assessed. The counts at the production day were excellent in three meals out of four, whereas one had high levels of spoilage and pathogens both as soon as the preparation and after seven days. MAP was partially effective only against the growth of the aerobic mesophilic species, whereas sensory analysis revealed that MAP may preserve many of sensory attributes. The average shelf-life of the meals ranged from 11 to 13 days, however, the potential shelf-life was undetectable in one out four meals, as L. monocytogenes growth was inhibited two days after the inoculum. In the inoculated meals, MW heating provided a partial inactivation (25%) of the pathogen. The overall quality of type the meals was partially satisfactory, post-cooking contaminations may affect the microbial load and reduce the palatability over the storage period and, above all, may involve biological hazards which consumers’ habits may not be able to eliminate.

Among typical Portuguese sausages, the cacholeira blood sausage undoubtedly represents one of the most popular preparations. To the authors' knowledge, a lack of information on both the microbiota and the volatile organic compounds (VOCs) of this blood-containing sausage emerges from the available scientific literature. This study represents the first characterization of physico-chemical, microbiological and volatile traits of Portuguese cacholeira blood sausage. To this end, ready-to-eat cacholeira blood sausages were collected from two production batches manufactured in summer (batch 1) and autumn (batch 2). Viable counts showed active microbial communities mainly composed by lactic acid bacteria, coagulase negative cocci, enterococci and eumycetes. The metataxonomic approach showed a simple bacterial composition, which was dominated by Lactobacillus sakei in both the analyzed batches (1 and 2) considered. Carnobacterium, Enterococcus, Kluyvera, Lactococcus and Serratia were found as minor genera. The mycobiota varied according to the production season. Batch 1 was dominated by Starmerella apicola, Debaryomyces hansenii and Candida tropicalis, whereas batch 2 was dominated by D. hansenii. Moreover, Aspergillus spp., Kurtzmaniella zeylanoides, Saccharomyces cerevisiae, Kurtzmaniella santamariae, Brettanomyces bruxellensis and Pichia kluyveri were detected in both the batches as minority species. Seventy-two volatile compounds were identified, including esters, phenols, terpenoids, acids, alcohols, ketones, aldehydes, lactones, furans, sulphur and nitrogen compounds. Significant differences were seen in the amount of some compounds, as a feasible consequence of differences in the raw materials, artisan production and seasonality.

Identifying cancer drivers and actionable mutations is critical for precision oncology. In epithelial ovarian cancer (EOC) the majority of mutations lack biological or clinical validation. We fully characterized 43 lines of Patient-Derived Xenografts (PDXs) and performed copy number analysis and whole exome sequencing of 12 lines derived from na&iuml, ve, high grade EOCs. Pyrosequencing allowed quantifying mutations in the source tumours. Drug response was assayed on PDX Derived Tumour Cells (PDTCs) and in vivo on PDXs. We identified a PIK3R1W624R variant in PDXs from a high grade serous EOC. Allele frequencies of PIK3R1W624R in all the passaged PDXs and in samples of the source tumour suggested that it was truncal and thus possibly a driver mutation. After inconclusive results in silico analyses, PDTCs and PDXs allowed the showing actionability of PIK3R1W624R and addiction of PIK3R1W624R carrying cells to inhibitors of the PI3K/AKT/mTOR pathway. It is noteworthy that PIK3R1 encodes the p85&alpha, regulatory subunit of PI3K, that is very rarely mutated in EOC. The PIK3R1W624R mutation is located in the cSH2 domain of the p85&alpha, that has never been involved in oncogenesis. These data show that patient-derived models are irreplaceable in their role of unveiling unpredicted driver and actionable variants in advanced ovarian cancer.

Following the first isolation of Brucella ceti from a bottlenose dolphin ( Tursiops truncatus ) fetus,1 several cases of B ceti infection were reported among free-ranging cetaceans worldwide.2 These included cases in the Mediterranean sea, where B ceti infection was first described in 2009.3 As with other Brucella genus members, B ceti displays a zoonotic capability4– prominent central nervous system (CNS) involvement in B ceti infection is commonly seen in striped dolphins ( Stenella coeruleoalba ) and in people,2, 5 but …

Introduction The quantitative determination of urinary Cystatin C (cyst-C) associated with the qualitative analysis of its polymorphisms is an excellent method for early identification of newborns predisposed to renal function impairment. PETIA, PENIA and EIA are the immunometric methods used for the quantitative determination of cyst-C in human biologic fluid but they have limitations and do not allow qualitative analysis. The present study is a validation of Immunoblot SDS-PAGE for the qualitative and quantitative analysis of urinary cyst-C. Methods Urine was collected from neonates in the nursey at S. Maria della Misericordia Hospital. Urinary cyst-C was investigated by the immunoblot SDS-PAGE and by reading of optical density. Results The qualitative analysis showed two different molecular forms: a reactivity at about 70 KDa in all samples and a reactivity at 13 KDa in a limited number of samples. This analysis allows the correlation of the polymorphisms of cyst-C with specific alterations of renal function in newborns. The quantitative analysis is specific, sensitive and accurate. In fact the coefficient of variation for assay precision was 10% and for assay accuracy was ±10%, the detection limit was 0.009 ng/ µL and the calibration line has satisfactory linearity (range 0.02–0.3 ng/ µL). The stability of urinary cyst-C was acceptable, even without the use of protease inhibitors, as long as the assay was performed on freshly recruited urine or immediately after thawing the samples, which had been stored for up to six months. Conclusion Immunoblot SDS-PAGE analysis is a valid method of obtaining a qualitative and quantitative analysis of urinary cyst-C. This method presents unique information about a previously unknown 70 KDa cyst-C form. The assay may offer potential diagnostic information not available with immunometric method.

One hundred lactic acid bacteria from Italian sourdoughs were characterized for technological features and selected for their tolerance to stress conditions commonly encountered within the production of leavened fermented bakery products. Specifically, lactic acid bacteria belonging to the family Lactobacillaceae were evaluated for the capability to withstand acidic conditions (pH 3.5, 4.0, 4.5, 5.5, 6.5) and to cope with different concentrations of NaCl (2, 3, 4, 5, 6, 8%), ethanol (2, 4, and 6%) and sucrose (20 and 30%) during 48 h fermentation. Strains were also tested for urease, amylase, proteolytic activities and for the capability to produce exopolysaccharides. The strains had a wide diversity in stress response pattern. Fructilactobacillus sanfranciscensis PE4, Furfurilactobacillus rossiae PS48, Levilactobacillus brevis PA6 and two strains of Leuconostoc pseudomesentereoides (PW2 and PD4) showed the highest survival to stress treatments and interesting technological properties (i.e. amino acid and exopolysaccharides production). Several strains exhibited high robustness also to strongest stress conditions, suggesting their potential use for applications in bakery industry. This study confirms the diversity of lactic acid bacteria to stress treatments and proposes suitable criteria for selection of competitive strains to be used in versatile way for production of different salty and sweetened leavened bakery products.

Donkey milk represents an attractive solution as new-born feeding, mainly if occur physiological limitations concerning the milk availability in post-pregnancy or bovine’s milk proteins linked to immune diseases. At present, the producers use custom-made batch pasteurization plant, with a poor temperature control system and very high time required to carry out the pasteurization process. It is due to the low availability of raw materials due to limited donkey livestock and low milk’s yield and the lack of high technology UHT pasteurization plants with limited processing capacity. In this work, an innovative low capability (30 l/h) continuous flow pasteurization plant, designed and built for High Temperature for Short Time (HTST) treatments, was characterized in the MACLab of UNIBAS. To test the plant, a matrix with three pasteurization temperatures (75, 85, 92 °C) and times (3, 7, 14 s) was tested, and the efficacy of the treatments was evaluated on microflora enumeration (L. monocytgenens, Enterobacteriaceae, total aerobic bacteria) as soon as after the treatments and over 30 days-storage at 4 °C. The HTST apparatus showed high performance; the complete eradication of Enterobacteriaceae detected the efficacy of the treatments at every time and temperatures tested. Decreasing in total bacterial count and lysozyme content was affected by treatment size. Through this methodological approach, it was possible to investigate the effect of HTST treatments (following by cooling soon) on the primary chemical and microbiological standard for donkey milk, to set up an official sanitation protocol that allows optimizing its nutritional value.

Dolphin morbillivirus (DMV) is considered an emerging threat having caused several epidemics worldwide. Only few DMV genomes are publicly available. Here, we report the use of target enrichment directly from cetacean tissues to obtain novel DMV genome sequences, with sequence comparison and phylodynamic analysis. RNA from 15 tissue samples of cetaceans stranded along the Italian and French coasts (2008–2017) was purified and processed using custom probes (by bait hybridization) for target enrichment and sequenced on Illumina MiSeq. Data were mapped against the reference genome, and the novel sequences were aligned to the available genome sequences. The alignment was then used for phylogenetic and phylogeographic analysis using MrBayes and BEAST. We herein report that target enrichment by specific capture may be a successful strategy for whole-genome sequencing of DMV directly from field samples. By this strategy, 14 complete and one partially complete genomes were obtained, with reads mapping to the virus up to 98% and coverage up to 7800X. The phylogenetic tree well discriminated the Mediterranean and the NE-Atlantic strains, circulating in the Mediterranean Sea and causing two different epidemics (2008–2015 and 2014–2017, respectively), with a limited time overlap of the two strains, sharing a common ancestor approximately in 1998.

Background Parasites of the family Spirorchiidae cause disease and mortality in marine and freshwater turtles; two species, Hapalotrema mistroides and Neospirorchis sp., are reported in the resident population of loggerhead turtles of the Mediterranean Sea, with the first being the most widespread. In vivo diagnosis of spirorchidiasis can represent a challenge in guaranteeing prompt control and treatment of the disease and is currently limited to copromicroscopy. The aim of this study was the development of a real time PCR assay with TaqMan probe for the detection of H. mistroides infection in the blood of live loggerhead turtles, Caretta caretta, hospitalized in rehabilitation centres. Its potential use for in vivo diagnosis is explored. Results The developed real time PCR successfully detected H. mistroides DNA from both positive controls and experimental blood samples of live loggerhead sea turtles, showing good specificity, sensitivity and good reaction efficiency. Two out of three turtles which had demonstrated positivity at copromicroscopy also tested positive to this blood assay; DNA of H. mistroides was detected within the blood of one sea turtle, which tested negative for copromicroscopy. Conclusions This study describes a specific and rapid molecular assay to detect H. mistroides infection from live sea turtles and highlights for the first time the presence of DNA of this species in turtle blood samples. Since this assay is able to detect low amounts of the parasitic free DNA in blood samples, its application could be helpful for in vivo diagnosis of H. mistroides infection as well as for epidemiological purposes.

Quantitative calcareous plankton analyses have been performed at the Ocean Drilling Program Site 977 in the Alboran Sea through the mid-Brunhes interval (300–540 ka). The results evidence orbital-suborbital and millennial scale climate variability which primary reflects temperature change. The patterns of increase/decrease of coccolithophore and planktonic foraminifera warm water taxa reproduce the stage and substage climate variability in the planktonic δ18O in good agreement with other planktonic isotope records from Mediterranean Sea and Atlantic Ocean. Variable conditions, characterized by alternating cool nutrient-rich or warm and stable sea-surface waters, occurred during interglacial Marine Isotope Stage (MIS) 13 in response to high amplitude oscillations of insolation during obliquity maximum and to North Africa monsoon strength, influencing distribution of taxa. MIS 13a resulted warmer than MIS 13c based on the higher abundances of warm water taxa; they increase just after insolation maxima, suggesting a primary response of calcareous plankton to precessional orbital control. Following short-term warm (MIS 11e) and more humid (MIS 11d) phases, a climate optimum lasting about 16 kyr is recognized during MIS 11c, when major tropical-subtropical water arrival into the Alboran Sea occurred as evidenced by the presence of Trilobatus sacculifer. MIS 11c records unstable climate condition that persisted up to the late MIS 11, indicating multiple pulses of southward migrations of subpolar front following the full interglacial MIS 11c. Warm and oligotrophic conditions occurred during MIS 9 as during MIS 11, especially in MIS 9e, although without a climate optimum. Reduced abundance of warm water taxa and decrease of Globorotalia inflata highlight colder surface water conditions and decreased Atlantic-Mediterranean water exchange during glacials, especially during the prominent sea-level low-stand of MIS 12. Short-term prominent peaks of the polar-subpolar Neogloboquadrina pachyderma and Coccolithus pelagicus ssp. pelagicus, and additional key taxa preferring fresher and turbid water, together with minima in total Nannofossil Accumulation Rate and enhanced coccolith reworking, sustain a correlation with the North Atlantic Heinrich-type (Ht) events Ht1, Ht1a, Ht3, Ht4-6, thus documenting the sensitiveness of the Alboran Sea in recording European and Laurentide ice-sheet dynamics. The comparable chronology of most of these cold spells in the available Balearic and Ionian calcareous plankton records highlights that Atlantic melt water entering Alboran basin through Gibraltar Strait may have reached the central Mediterranean preserving some of its original polar signature.

Stem cells have high potential for cell therapy in regenerative medicine. We previously isolated stem cell types from human amniotic fluid, derived from prenatal amniocentesis. One type, characterized by a fast doubling time, was designated as fast human amniotic stem cells (fHASCs). These cells exhibited high differentiation potential and immunoregulatory properties. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite that influences stem-cell pluripotency, differentiation, mobility, and regulates immune functions. In this study, we investigated the influence of S1P on fHASC migration, proliferation, differentiation and immune regulatory functions. We found that fHASC stimulation with S1P potentiated their migratory and proliferative activity in vitro. Notably, short fHASC exposure to S1P enhanced their differentiation towards multiple lineages, including adipocytes, osteocytes and endothelial cells, an effect that was associated with downregulation of the main transcription factors involved in the maintenance of a stem-cell undifferentiated state. A specific crosstalk between S1P and tumor growth factor β1 (TGF-β1) has recently been demonstrated. We found that fHASC exposure to S1P in combination with TGF-β1 promoted the expression of the immune regulatory pathway of indoleamine 2,3-dioxygenase 1 (IDO1). In addition, human peripheral blood mononuclear cells, co-cultured with fHASCs treated with S1P and TGF-β1, expanded regulatory T-cells, via a mechanism requiring IDO1. Overall, this study demonstrates that S1P potentiates several properties in fHASCs, an effect that may be critical for exploiting the therapeutic potential of fHASCs and might explain the specific effects of S1P on stem cells during pregnancy., Graphical abstract fx1

Background and Purpose— The small ubiquitin-like modifier (SUMO), a ubiquitin-like protein involved in posttranslational protein modifications, is activated by several conditions, such as heat stress, hypoxia, and hibernation and confers neuroprotection. Sumoylation enzymes and substrates are expressed also at the plasma membrane level. Among the numerous plasma membrane proteins controlling ionic homeostasis during cerebral ischemia, 1 of the 3 brain sodium/calcium exchangers (NCX3), exerts a protective role during ischemic preconditioning. In this study, we evaluated whether NCX3 is a target for sumoylation and whether this posttranslational modification participates in ischemic preconditioning-induced neuroprotection. To test these hypotheses, we analyzed (1) SUMO1 conjugation pattern after ischemic preconditioning; (2) the effect of SUMO1 knockdown on the ischemic damage after transient middle cerebral artery occlusion and ischemic preconditioning, (3) the possible interaction between SUMO1 and NCX3 and (4) the molecular determinants of NCX3 sequence responsible for sumoylation. Methods— Focal brain ischemia and ischemic preconditioning were induced in rats by middle cerebral artery occlusion. SUMOylation was evaluated by western blot and immunohistochemistry. SUMO1 and NCX3 interaction was analyzed by site-directed mutagenesis and immunoprecipitation assay. Results— We found that (1) SUMO1 knockdown worsened ischemic damage and reduced the protective effect of preconditioning; (2) SUMO1 bound to NCX3 at lysine residue 590, and its silencing increased NCX3 degradation; and (3) NCX3 sumoylation participates in SUMO1 protective role during ischemic preconditioning. Thus, our results demonstrate that NCX3 sumoylation confers additional neuroprotection in ischemic preconditioning. Conclusions— Finally, this study suggests that NCX3 sumoylation might be a new target to enhance ischemic preconditioning-induced neuroprotection.

Na+-Ca2+ exchanger (NCX) isoforms constitute the major cellular Ca2+ extruding system in neurons and microglia. We herein investigated the role of NCX isoforms in the pathophysiology of Parkinson’s disease (PD). Their expression and activity were evaluated in neurons and glia of mice expressing the human A53T variant of α-synuclein (A53T mice), an animal model mimicking a familial form of PD. Western blotting revealed that NCX3 expression in the midbrain of 12-month old A53T mice was lower than that of wild type (WT). Conversely, NCX1 expression increased in the striatum. Immunohistochemical studies showed that glial fibrillary acidic protein (GFAP)-positive astroglial cells significantly increased in the substantia nigra pars compacta (SNc) and in the striatum. However, the number and the density of tyrosine hydroxylase (TH)-positive neurons decreased in both brain regions. Interestingly, ionized calcium binding adaptor molecule 1 (IBA-1)-positive microglial cells increased only in the striatum of A53T mice compared to WT. Double immunostaining studies showed that in A53T mice, NCX1 was exclusively co-expressed in IBA-1-positive microglial cells in the striatum, whereas NCX3 was solely co-expressed in TH-positive neurons in SNc. Beam walking and pole tests revealed a reduction in motor performance for A53T mice compared to WT. In vitro experiments in midbrain neurons from A53T and WT mice demonstrated a reduction in NCX3 expression, which was accompanied by mitochondrial overload of Ca2+ ions, monitored with confocal microscopy by X-Rhod-1 fluorescent dye. Collectively, in vivo and in vitro findings suggest that the reduction in NCX3 expression and activity in A53T neurons from midbrain may cause mitochondrial dysfunction and neuronal death in this brain area, whereas NCX1 overexpression in microglial cells may promote their proliferation in the striatum.