Point-of-Care Bedside Brain Magnetic Resonance Imaging Is Safe in Extracorporeal Membrane Oxygenation Patients With Swan Ganz Catheters: A Phantom Experiment and Single Center Experience.

INTRODUCTION: More than 1.2 million pulmonary artery catheters (PACs) are used in cardiac patients per annum within the United States. However, it is contraindicated in traditional 1.5 and 3T magnetic resonance imaging (MRI) scans. We aimed to test preclinical and clinical safety of using this imaging modality given the potential utility of needing it in the clinical setting. METHODS: We conducted two phantom experiments to ensure that the electromagnetic field power deposition associated with bare and jacketed PACs was safe and within the acceptable limit established by the Food and Drug Administration. The primary end points were the safety and feasibility of performing Point-of-Care (POC) MRI without imaging-related adverse events. We performed a preclinical computational electromagnetic simulation and evaluated these findings in nine patients with PACs on veno-arterial extracorporeal membrane oxygenation. RESULTS: The phantom experiments showed that the baseline point specific absorption rate through the head averaged 0.4 W/kg. In both the bare and jacketed catheters, the highest net specific absorption rates were at the neck entry point and tip but were negligible and unlikely to cause any heat-related tissue or catheter damage. In nine patients (median age 66, interquartile range 42-72 y) with veno-arterial extracorporeal membrane oxygenation due to cardiogenic shock and PACs placed for close hemodynamic monitoring, POC MRI was safe and feasible with good diagnostic imaging quality. CONCLUSIONS: Adult ECMO patients with PACs can safely undergo point-of-care low-field (64 mT) brain MRI within a reasonable timeframe in an intensive care unit setting to assess for acute brain injury that might otherwise be missed with conventional head computed tomography.

Comprehensive chemotaxonomic and genomic profiling of a biosynthetically talented Australian fungus, Aspergillus burnettii sp. nov.

Aspergillus burnettii is a new species belonging to the A. alliaceus clade in Aspergillus subgenus Circumdati section Flavi isolated from peanut-growing properties in southern Queensland, Australia. A. burnettii is a fast-growing, floccose fungus with distinctive brown conidia and is a talented producer of biomass-degrading enzymes and secondary metabolites. Chemical profiling of A. burnettii revealed the metabolites ochratoxin A, kotanins, isokotanins, asperlicin E, anominine and paspalinine, which are common to subgenus Circumdati, together with burnettiene A, burnettramic acids, burnettides, and high levels of 14α-hydroxypaspalinine and hirsutide. The genome of A. burnettii was sequenced and an annotated draft genome is presented. A. burnettii is rich in secondary metabolite biosynthetic gene clusters, containing 51 polyketide synthases, 28 non-ribosomal peptide synthetases and 19 genes related to terpene biosynthesis. Functional annotation of digestive enzymes of A. burnettii and A. alliaceus revealed overlapping carbon utilisation profiles, consistent with a close phylogenetic relationship.

Fungal communities in rice cultivated in different Brazilian agroclimatic zones: From field to market.

Rice is one of the most consumed cereals in Brazil and around the world. Due to the major health impact of rice consumption on populations, studies about its quality have great importance. The present study determined the mycobiota of soil, field, processing and market rice samples from two production systems in Brazil, dryland in the state of Maranhão and wetland in the state of Rio Grande do Sul. These areas are distinct agroclimatic zones. A total of 171 rice and 23 soil samples were analyzed. A high differentiation was observed in the composition of the fungal communities found in the two production systems, as the wetland presented greater fungal incidence and biodiversity. It was observed that toxigenic species from Aspergillus section Flavi and Fusarium, present in the field, may infect rice grains pre or postharvest and may persist into the final product.

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis.

Chemical investigation of an undescribed Australian fungus, Aspergillus nanangensis, led to the identification of the nanangenines - a family of seven new and three previously reported drimane sesquiterpenoids. The structures of the nanangenines were elucidated by detailed spectroscopic analysis supported by single crystal X-ray diffraction studies. The compounds were assayed for in vitro activity against bacteria, fungi, mammalian cells and plants. Bioinformatics analysis, including comparative analysis with other acyl drimenol-producing Aspergilli, led to the identification of a putative nanangenine biosynthetic gene cluster that corresponds to the proposed biosynthetic pathway for nanangenines.

Banksialactones and Banksiamarins: Isochromanones and Isocoumarins from an Australian Fungus, Aspergillus banksianus.

Chemical investigation of an Australian fungus, Aspergillus banksianus, led to the isolation of the major metabolite banksialactone A (1), eight new isochromanones, banksialactones B-I (2-9), two new isocoumarins, banksiamarins A and B (10 and 11), and the reported compounds, clearanol I (12), dothideomynone A (13), questin (14), and endocrocin (15). The structures of 1-11 were established by NMR spectroscopic data analysis, and the absolute configurations were determined from optical rotations and ECD spectra in conjunction with TD-DFT calculations. The secondary metabolite profile of A. banksianus is unusual, with the 11 most abundant metabolites belonging to a single isochromanone class. Conjugation of 1 with endocrocin, 5-methylorsellinic acid, 3,5-dimethylorsellinic acid, mercaptolactic acid, and an unknown methylthio source gave rise to five unprecedented biosynthetic hybrids, 5-9. The isolated compounds were tested for cytotoxicity, antibacterial, and antifungal activities, with hybrid metabolites 7-9 displaying weak cytotoxic and antibiotic activities.

Genomic insights into the carbohydrate catabolism of Cairneyella variabilis gen. nov. sp. nov., the first reports from a genome of an ericoid mycorrhizal fungus from the southern hemisphere.

This paper describes a novel species of ericoid mycorrhizal fungus from Australia, Cairneyella variabilis, Midgley and Tran-Dinh, gen. nov. sp. nov. The genome of C. variabilis was sequenced and a draft genome assembled. The draft genome of C. variabilis is 52.4 Mbp in length, and to our knowledge, this is the first study to present a genome of an ericoid mycorrhizal fungus from the southern hemisphere. Using the SignalP and dbCAN bioinformatic pipelines, a study of the catabolic potential of C. variabilis was undertaken and showed genes for an array of degradative enzymes, most of which appear to be secreted from the hyphae, to access a suite of different carbon sources. Isolates of C. variabilis have been previously shown to utilise cellulose, carboxymethyl cellulose (CMC), cellobiose, xylan, pectin, starch and tannic acid for growth, and in the current study, putative enzymes for these processes were revealed. These enzymes likely play key roles in nutrient cycling and other edaphic processes in heathland environments. ITS phylogenetic analyses showed C. variabilis to be distinct from the fungi of the "Hymenoscyphus ericae aggregate".

Name changes in medically important fungi and their implications for clinical practice.

Recent changes in the Fungal Code of Nomenclature and developments in molecular phylogeny are about to lead to dramatic changes in the naming of medically important molds and yeasts. In this article, we present a widely supported and simple proposal to prevent unnecessary nomenclatural instability.

Aspergillus, its sexual states and the new International Code of Nomenclature.

The newly adopted International Code of Nomenclature for algae, fungi and plants (ICN) demands that dimorphic fungi, in particular those with both sexual and asexual names, now bear a single name. Although priority is no longer associated with the mode of reproduction, the ICN requires justification for choosing an asexual name over an existing sexual one. The phylogenetic approach that made dual nomenclature for fungi obsolete can be used to help choose names for large groups of fungi that are best known by asexual names. Here we apply this approach to one of the largest and most diverse asexual genera, the genus Aspergillus. We find that existing sexual names may be given to well supported clades of fungi with distinct phenotypes, which include sexual morphology as well as physiological attributes associated with xerophily, thermophily and mycotoxin production. One group of species important to food production and food safety, Aspergillus subgen. Circumdati, lacks a well supported clade; here we propose that the name Aspergillus be retained for this group. Recognizing that nomenclature has economic and social implications, particularly for old, important genera, we discuss the consequences of various scenarios to implement the new "one name for one fungus" article in the ICN, showing that our approach requires the fewest appeals to the ICN while retaining the name Aspergillus for many of the most economically and socially important species.

Understanding Mycotoxin Contamination Across the Food Chain in Brazil: Challenges and Opportunities.

Brazil is one of the largest food producers and exporters in the world. In the late 20th century, the European Union program for the harmonization of regulations for contaminants in food, including mycotoxins, led to the examination of mycotoxin contamination in foods at a global level. The problem of the rejection of food by the European Union and other countries became a Brazilian national priority because of economic and food safety aspects. Ochratoxin A in coffee and cocoa and aflatoxins in Brazil nuts are examples of the impact of technical trade barriers on Brazilian foods. To overcome these threats, several strategies were undertaken by Brazilian and international organizations. In this context, the Codex Commission on Food Contaminants (CCCF) has emerged as a forum to discuss with more transparency issues related to mycotoxins, focusing on establishing maximum levels and codes of practices for some commodities and mycotoxins to ensure fair trade and food safety. Our experience in investigating and understanding mycotoxin contamination across the food chains in Brazil has contributed nationally and internationally to providing some answers to these issues.

Discovery and Heterologous Biosynthesis of the Burnettramic Acids: Rare PKS-NRPS-Derived Bolaamphiphilic Pyrrolizidinediones from an Australian Fungus, Aspergillus burnettii.

The burnettramic acids are a new class of antibiotics from an Australian fungus Aspergillus burnettii. The rare bolaamphiphilic scaffold consists of ß-d-mannose linked to a pyrrolizidinedione unit via a 26-carbon chain. The most abundant metabolite displayed potent in vitro antifungal activity. Comparative genomics identified the hybrid PKS-NRPS bua gene cluster, which was verified by heterologous pathway reconstitution in Aspergillus nidulans.

Occurrence of Aspergillus section Flavi and aflatoxins in Brazilian rice: From field to market.

The guarantee of the high quality of rice is of utmost importance because any toxic contaminant may affect consumer health, especially in countries such as Brazil where rice is part of the daily diet. A total of 187 rice samples, from field, processing and market from two different production systems, wetland from the state of Rio Grande do Sul, dryland, from the state of Maranhão and market samples from the state of São Paulo, were analyzed for fungi belonging to Aspergillus section Flavi and the presence of aflatoxins. Twenty-three soil samples from wetland and dryland were also analyzed. A total of 383 Aspergillus section Flavi strains were isolated from rice and soil samples. Using a polyphasic approach, with phenotypic (morphology and extrolite profiles) and molecular data (beta-tubulin gene sequences), five species were identified: A. flavus, A. caelatus, A. novoparasiticus, A. arachidicola and A. pseudocaelatus. This is the first report of these last three species from rice and rice plantation soil. Only seven (17%) of the A. flavus isolates produced type B aflatoxins, but 95% produced kojic acid and 69% cyclopiazonic acid. Less than 14% of the rice samples were contaminated with aflatoxins, but two of the market samples were well above the maximum tolerable limit (5µg/kg), established by the Brazilian National Health Surveillance Agency.

A Concise History of Mycotoxin Research.

Toxigenic fungi and mycotoxins entered human food supplies about the time when mankind first began to cultivate crops and to store them from one season to the next, perhaps 10,000 years ago. The storage of cereals probably initiated the transition by mankind from hunter-gatherer to cultivator, at the same time providing a vast new ecological niche for fungi pathogenic on grain crops or saprophytic on harvested grain, many of which produced mycotoxins. Grains have always been the major source of mycotoxins in the diet of man and his domestic animals. In the historical context, ergotism from Claviceps purpurea in rye has been known probably for more than 2000 years and caused the deaths of many thousands of people in Europe in the last millennium. Known in Japan since the 17th century, acute cardiac beriberi associated with the consumption of moldy rice was found to be due to citreoviridin produced by Penicillium citreonigrum. This toxin was believed to be only of historic importance until its reemergence in Brazil a few years ago. Other Penicillium toxins, including ochratoxin A, once considered to be a possible cause of Balkan endemic nephropathy, are treated in a historical context. The role of Fusarium toxins in human and animal health, especially T-2 toxin in alimentary toxic aleukia in Russia in the 1940s and fumonisins in equine leucoencephalomalasia, is set out in some detail. Finally, this paper documents the story of the research that led to our current understanding of the formation of aflatoxins in grains and nuts, due to the growth of Aspergillus flavus and its role, in synergy with the hepatitis B virus, in human liver cancer. During a period of climate change and greatly reduced crop diversity on a global basis, researchers tasked with monitoring the food system need to be aware of fungal toxins that might have been rare in their working careers that can reappear.

The roles of endolithic fungi in bioerosion and disease in marine ecosystems. II. Potential facultatively parasitic anamorphic ascomycetes can cause disease in corals and molluscs.

Anamorphic ascomycetes have been implicated as causative agents of diseases in tissues and skeletons of hard corals, in tissues of soft corals (sea fans) and in tissues and shells of molluscs. Opportunist marine fungal pathogens, such as Aspergillus sydowii, are important components of marine mycoplankton and are ubiquitous in the open oceans, intertidal zones and marine sediments. These fungi can cause infection in or at least can be associated with animals which live in these ecosystems. A. sydowii can produce toxins which inhibit photosynthesis in and the growth of coral zooxanthellae. The prevalence of many documented infections has increased in frequency and severity in recent decades with the changing impacts of physical and chemical factors, such as temperature, acidity and eutrophication. Changes in these factors are thought to cause significant loss of biodiversity in marine ecosystems on a global scale in general, and especially in coral reefs and shallow bays.

The roles of endolithic fungi in bioerosion and disease in marine ecosystems. I. General concepts.

Endolithic true fungi and fungus-like microorganisms penetrate calcareous substrates formed by living organisms, cause significant bioerosion and are involved in diseases of many host animals in marine ecosystems. A theoretical interactive model for the ecology of reef-building corals is proposed in this review. This model includes five principle partners that exist in a dynamic equilibrium: polyps of a colonial coelenterate, endosymbiotic zooxanthellae, endolithic algae (that penetrate coral skeletons), endolithic fungi (that attack the endolithic algae, the zooxanthellae and the polyps) and prokaryotic and eukaryotic microorganisms (which live in the coral mucus). Endolithic fungi and fungus-like boring microorganisms are important components of the marine calcium carbonate cycle because they actively contribute to the biodegradation of shells of animals composed of calcium carbonate and calcareous geological substrates.

Kinetics of aflatoxin degradation during peanut roasting.

This study investigated aflatoxin degradation during peanut roasting. First, peanuts contaminated with three initial aflatoxin concentrations (35, 332 and 695µg/kg) were roasted at 180°C for up to 20min. The percentage of aflatoxin degradation after 20min were 55, 64 and 81% for peanuts contaminated with aflatoxin at 35, 332 and 695µg/kg, respectively. This difference was statistically significant (p<0.05), showing that initial concentration influences aflatoxin reduction. Thereafter, peanut samples contaminated with an initial aflatoxin concentration of 85µg/kg were roasted at 160, 180 and 200°C for 5, 10, 15, 20 and 25min, then residual concentrations of aflatoxin were determined. Roasting at 160, 180 and 200°C resulted in an aflatoxin reduction of 61.6, 83.6 and 89.7%, respectively. This study has provided quantitative data reinforcing the fact that roasting alone is not enough to control aflatoxins in peanuts.

Discovery of Aspergillus frankstonensis sp. nov. during environmental sampling for animal and human fungal pathogens.

Invasive fungal infections (IFI) due to species in Aspergillus section Fumigati (ASF), including the Aspergillus viridinutans species complex (AVSC), are increasingly reported in humans and cats. The risk of exposure to these medically important fungi in Australia is unknown. Air and soil was sampled from the domiciles of pet cats diagnosed with these IFI and from a nature reserve in Frankston, Victoria, where Aspergillus viridinutans sensu stricto was discovered in 1954. Of 104 ASF species isolated, 61% were A. fumigatus sensu stricto, 9% were AVSC (A. felis-clade and A. frankstonensis sp. nov.) and 30% were other species (30%). Seven pathogenic ASF species known to cause disease in humans and animals (A. felis-clade, A. fischeri, A. thermomutatus, A. lentulus, A. laciniosus A. fumisynnematus, A. hiratsukae) comprised 25% of isolates overall. AVSC species were only isolated from Frankston soil where they were abundant, suggesting a particular ecological niche. Phylogenetic, morphological and metabolomic analyses of these isolates identified a new species, A. frankstonensis that is phylogenetically distinct from other AVSC species, heterothallic and produces a unique array of extrolites, including the UV spectrum characterized compounds DOLD, RAIMO and CALBO. Shared morphological and physiological characteristics with other AVSC species include slow sporulation, optimal growth at 37°C, no growth at 50°C, and viriditoxin production. Overall, the risk of environmental exposure to pathogenic species in ASF in Australia appears to be high, but there was no evidence of direct environmental exposure to AVSC species in areas where humans and cats cohabitate.

Aspergillus hancockii sp. nov., a biosynthetically talented fungus endemic to southeastern Australian soils.

Aspergillus hancockii sp. nov., classified in Aspergillus subgenus Circumdati section Flavi, was originally isolated from soil in peanut fields near Kumbia, in the South Burnett region of southeast Queensland, Australia, and has since been found occasionally from other substrates and locations in southeast Australia. It is phylogenetically and phenotypically related most closely to A. leporis States and M. Chr., but differs in conidial colour, other minor features and particularly in metabolite profile. When cultivated on rice as an optimal substrate, A. hancockii produced an extensive array of 69 secondary metabolites. Eleven of the 15 most abundant secondary metabolites, constituting 90% of the total area under the curve of the HPLC trace of the crude extract, were novel. The genome of A. hancockii, approximately 40 Mbp, was sequenced and mined for genes encoding carbohydrate degrading enzymes identified the presence of more than 370 genes in 114 gene clusters, demonstrating that A. hancockii has the capacity to degrade cellulose, hemicellulose, lignin, pectin, starch, chitin, cutin and fructan as nutrient sources. Like most Aspergillus species, A. hancockii exhibited a diverse secondary metabolite gene profile, encoding 26 polyketide synthase, 16 nonribosomal peptide synthase and 15 nonribosomal peptide synthase-like enzymes.

Penicillium excelsum sp. nov from the Brazil Nut Tree Ecosystem in the Amazon Basin'.

A new Penicillium species, P. excelsum, is described here using morphological characters, extrolite and partial sequence data from the ITS, ß-tubulin and calmodulin genes. It was isolated repeatedly using samples of nut shells and flowers from the brazil nut tree, Bertolletia excelsa, as well as bees and ants from the tree ecosystem in the Amazon rainforest. The species produces andrastin A, curvulic acid, penicillic acid and xanthoepocin, and has unique partial ß-tubulin and calmodulin gene sequences. The holotype of P. excelsum is CCT 7772, while ITAL 7572 and IBT 31516 are cultures derived from the holotype.

World Health Organization estimates of the global and regional disease burden of four foodborne chemical toxins, 2010: a data synthesis.

Background Chemical exposures have been associated with a variety of health effects; however, little is known about the global disease burden from foodborne chemicals. Food can be a major pathway for the general population's exposure to chemicals, and for some chemicals, it accounts for almost 100% of exposure.  Methods and Findings Groups of foodborne chemicals, both natural and anthropogenic, were evaluated for their ability to contribute to the burden of disease.  The results of the analyses on four chemicals are presented here - cyanide in cassava, peanut allergen, aflatoxin, and dioxin.  Systematic reviews of the literature were conducted to develop age- and sex-specific disease incidence and mortality estimates due to these chemicals.  From these estimates, the numbers of cases, deaths and disability adjusted life years (DALYs) were calculated.  For these four chemicals combined, the total number of illnesses, deaths, and DALYs in 2010 is estimated to be 339,000 (95% uncertainty interval [UI]: 186,000-1,239,000); 20,000 (95% UI: 8,000-52,000); and 1,012,000 (95% UI: 562,000-2,822,000), respectively.  Both cyanide in cassava and aflatoxin are associated with diseases with high case-fatality ratios.  Virtually all human exposure to these four chemicals is through the food supply.  Conclusion Chemicals in the food supply, as evidenced by the results for only four chemicals, can have a significant impact on the global burden of disease. The case-fatality rates for these four chemicals range from low (e.g., peanut allergen) to extremely high (aflatoxin and liver cancer).  The effects associated with these four chemicals are neurologic (cyanide in cassava), cancer (aflatoxin), allergic response (peanut allergen), endocrine (dioxin), and reproductive (dioxin).