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INTRODUCTION: Hydroxychloroquine use in COVID-19 patients was widespread and uncontrolled until recently. Patients vulnerable to severe COVID-19 are at risk for hydroxychloroquine interactions with comorbidities and co-medications contributing to detrimental, including fatal adverse treatment effects. METHODS: This is a retrospective survey of health conditions and co-medications of COVID-19 patients who were pre-screened for enrolment into a randomized, double-blind, placebo-controlled hydroxychloroquine multicenter trial. RESULTS: Our survey involved 305 patients (median age 71 (IQR: 59-81) years). The majority of patients (N = 279, 92%) considered for inclusion into the clinical trial were not eligible mainly due to safety concerns caused by health conditions or co-medications. Most common were QT prolonging drugs (N = 188, 62%) and hematologic/hemato-oncologic diseases (N = 39, 13%) which prohibited the administration of hydroxychloroquine in our clinical trial. Additionally, 165 (54%) patients had health conditions and 167 (55%) were on co-medications that did not prohibit hydroxychloroquine treatment but had a risk of adverse interactions with hydroxychloroquine. Most common were diabetes (N = 86, 28%), renal insufficiency (N = 69, 23%) and heart failure (N = 58, 19%). CONCLUSION: The majority of hospitalized COVID-19 patients had health conditions or took co-medications precluding safe treatment with hydroxychloroquine. Therefore, especially in elderly, hydroxychloroquine should be administered with extreme caution and only in clinical trials.

Google's ‘Community Mobility Reports’ (CMR) detail changes in activity and mobility occurring in response to COVID-19. They thus offer the unique opportunity to examine the relationship between mobility and disease incidence. The objective was to examine whether an association between COVID-19-confirmed case numbers and levels of mobility was apparent, and if so then to examine whether such data enhance disease modelling and prediction. CMR data for countries worldwide were cross-correlated with corresponding COVID-19-confirmed case numbers. Models were fitted to explain case numbers of each country's epidemic. Models using numerical date, contemporaneous and distributed lag CMR data were contrasted using Bayesian Information Criteria. Noticeable were negative correlations between CMR data and case incidence for prominent industrialised countries of Western Europe and the North Americas. Continent-wide examination found a negative correlation for all continents with the exception of South America. When modelling, CMR-expanded models proved superior to the model without CMR. The predictions made with the distributed lag model significantly outperformed all other models. The observed relationship between CMR data and case incidence, and its ability to enhance model quality and prediction suggests data related to community mobility could prove of use in future COVID-19 modelling.

Scientific fields are always changing, and it is important to determine the directions in which they are heading as plans are made for future research activities and research results transition to applications and policies. The MycoKey project, an EU-funded Horizon 2020 project, includes a series of "Roundtable Discussions" to gather information from leading researchers inside and outside the project on directions in which the field of mycotoxicology is trending. This presentation includes a summary of the roundtable discussion on priorities and critical issues in chemical detection and monitoring of mycotoxins. The goal was to identify key elements that could impact when and how methods are used to identify mycotoxins and to increase food safety. The discussion was managed by using the Nominal Group discussion Technique (NGT). The NGT provides for equal input from all participants and is well-known as a process for generating a large number of ideas, while also providing a mechanism for ranking them. The discussion was focused on four following key questions: oto identify scientific and technological innovations which hold promise for development/improvement in the future (question 1); oto identify and prioritize critical elements making methods effectively applicable in -industry for autocontrol and HACCP (question 2), -developing countries with limited analytical capabilities (question 3), -official control with particular reference to multi-mycotoxin methods (question 4). The rankings and the total list of responses provided a rich and detailed context from which particular ideas and general trends could be extracted. Test kits, usually antibody based, were one major focus of the discussions because of their many favorable features, e.g., cost, speed, and ease of use. Most important was considered the degree to which antibody-based diagnostics have become an acceptable standard in many practical applications. Much of the discussion was on how to improve these kits and to speed the detection of mycotoxins in locations where access to a well-equipped analytical chemistry laboratory is neither timely nor cost-effective. The second area of focus for this discussion was multi-mycotoxin detection protocols and challenges remaining before these protocols become methods of choice for regulated mycotoxins. This second point mirrors the first, through the increasing importance of technically highly sophisticated multi-mycotoxin detection protocols. These protocols need more standardization and cross-laboratory validation, but are the future for many official regulatory controls, especially as the number of toxins that are regulated increases. Multi-mycotoxin assays are being developed at a large number of locations and international inter-laboratory validation and comparability of results are needed to establish credibility of results across both scientific and regulatory boundaries. Common critical factors for analyses in academic, industrial, and governmental laboratories and developing countries were speed, expense, accuracy/reliability, data management, and, particularly in developing countries, operator training. Finally, forging a partnership between scientists and well-placed communications experts was recognized as an essential step to communicating risks while retaining overall confidence in the safety of the food supply and the integrity of the food production chain. This work was supported by H2020- MycoKey-(E.U.3.2-678781)

Fungi of the genus Penicillium are promising sources of bioactive substances. Fungal strains isolated from poorly characterized habitais are currently under active investigation as potential producers of biologically active compounds. Penicillium nordicum is mostly known by its ability to produce the mycotoxin ochratoxin A in several protein- and salt-rich food matrices like processed meat and cheese, but it can also produce an array of other secondary metabolites. In a previous study, strains of this species were found to produce, under specific growth conditions, one unidentified compound in apparently big amounts, without producing ochratoxin A. The aim of the present study was to evaluate the bioactive properties of this compound in terms of antioxidant, antimicrobial, cytotoxic and herbicidal properties. For that purpose, the fungus was grown on ham-based médium and the aqueous extract of the compound was used for further tests. The extract showed significant effects on seed germination as well as on root and shoot growth of tomato, lettuce, wheat and oat. The root growth inhibition ranged from 74% to 98%, ana the shoot growth was reduced in 23 to 88%, being tomato the most sensitive plant. The extract did not show any cytotoxic activity in non-tumor porcine liver primary culture cells and human tumor cell lines. The antibacterial effect on human clinicai isolates and antifungal effect on foodbome and environmental isolates was also not significant. Pestalotin was the predominant compound in the fungal extract, with questiomycin and 7- hydroxypestalotin also being found at lower concentrations, as detected by Liquid Chromatography- Mass Spectrometry (HPLC-MS/MS) based multi-metabolite method. The extract was considered as a potential bioherbicide without noticeable negative effects on human and animal cells and also on the environment. Further tests on herbicidal potential are now under development. The authors are grateful to the Foundatton for Science and Technology (FCT, Portugal) anü FEDER under ProgrammePT2020 for financiai suppoit to CIMO (UID/AGR/00690/2013) info:eu-repo/semantics/publishedVersion

Secondary metabolites produced by fungi and bacteria are among the potential agents that contribute to adverse health effects observed in occupants of buildings affected by moisture damage, dampness and associated microbial growth. However, few attempts have been made to assess the occurrence of these compounds in relation to moisture damage and dampness in buildings. This study conducted in the context of the HITEA project (Health Effects of Indoor Pollutants: Integrating microbial, toxicological and epidemiological approaches) aimed at providing systematic information on the prevalence of microbial secondary metabolites in a large number of school buildings in three European countries, considering both buildings with and without moisture damage and/or dampness observations. In order to address the multitude and diversity of secondary metabolites a large number of more than 180 analytes was targeted in settled dust and surface swab samples using liquid chromatography/mass spectrometry (LC/MS) based methodology. While 42%, 58% and 44% of all samples collected in Spanish, Dutch and Finnish schools, respectively, were positive for at least one of the metabolites analyzed, frequency of detection for the individual microbial secondary metabolites - with the exceptions of emodin, certain enniatins and physcion - was low, typically in the range of and below 10% of positive samples. In total, 30 different fungal and bacterial secondary metabolites were found in the samples. Some differences in the metabolite profiles were observed between countries and between index and reference school buildings. A major finding in this study was that settled dust derived from moisture damaged, damp schools contained larger numbers of microbial secondary metabolites at higher levels compared to respective dust samples from schools not affected by moisture damage and dampness. This observation was true for schools in each of the three countries, but became statistically significant only when combining schools from all countries and thus increasing the sample number in the statistical analyses.

Secondary metabolites produced by fungi and bacteria are among the potential agents that contribute to adverse health effects observed in occupants of buildings affected by moisture damage, dampness and associated microbial growth. However, few attempts have been made to assess the occurrence of these compounds in relation to moisture damage and dampness in buildings. This study conducted in the context of the HITEA project (Health Effects of Indoor Pollutants: Integrating microbial, toxicological and epidemiological approaches) aimed at providing systematic information on the prevalence of microbial secondary metabolites in a large number of school buildings in three European countries, considering both buildings with and without moisture damage and/or dampness observations. In order to address the multitude and diversity of secondary metabolites a large number of more than 180 analytes was targeted in settled dust and surface swab samples using liquid chromatography/mass spectrometry (LC/MS) based methodology. While 42%, 58% and 44% of all samples collected in Spanish, Dutch and Finnish schools, respectively, were positive for at least one of the metabolites analyzed, frequency of detection for the individual microbial secondary metabolites - with the exceptions of emodin, certain enniatins and physcion - was low, typically in the range of and below 10% of positive samples. In total, 30 different fungal and bacterial secondary metabolites were found in the samples. Some differences in the metabolite profiles were observed between countries and between index and reference school buildings. A major finding in this study was that settled dust derived from moisture damaged, damp schools contained larger numbers of microbial secondary metabolites at higher levels compared to respective dust samples from schools not affected by moisture damage and dampness. This observation was true for schools in each of the three countries, but became statistically significant only when combining schools from all countries and thus increasing the sample number in the statistical analyses.

The occurrence of emerging Fusarium mycotoxins beauvericin (BEA), enniatins (ENNs) (A, A1, B, B1), Fusaproliferin and moniliformin was evaluated by a liquid chromatography/electrospray ionization-tandem mass spectrometric (LC/ESI-MS/MS) technique in 65 domestic rice samples produced in Gilan and Mazandaran Provinces in Iran. The results showed that 46% of the samples were contaminated with at least one of the emerging mycotoxins. BEA was the most prevalent mycotoxin, which was found in 26 out of 65 rice samples at the concentrations up to 0.47 µg/Kg. Enniatin A1 which was the only member of ENNs was detected in the samples, occurred in 7.7% of samples with an average level of 0.06 μg/Kg. No detectable level of Fusaproliferin and moniliformin was found. This is the first report concerning the contamination of Iranian domestic rice samples with the emerging Fusarium mycotoxins.

In this study, durum wheat kernels harvested in three climatically different Italian cultivation areas (Emilia Romagna, Umbria and Sardinia) in 2015, were analyzed with a combination of different isolation methods to determine their fungal communities, with a focus on Fusarium head blight (FHB) complex composition, and to detect fungal secondary metabolites in the grains. The genus Alternaria was the main component of durum wheat mycobiota in all investigated regions, with the Central Italian cultivation area showing the highest incidence of this fungal genus and of its secondary metabolites. Fusarium was the second most prevalent genus of the fungal community in all cultivation environments, even if regional differences in species composition were detected. In particular, Northern areas showed the highest Fusarium incidence, followed by Central and then Southern cultivation areas. Focusing on the FHB complex, a predominance of Fusarium poae, in particular in Northern and Central cultivation areas, was found. Fusarium graminearum, in the analyzed year, was mainly detected in Emilia Romagna. Because of the highest Fusarium incidence, durum wheat harvested in the Northern cultivation area showed the highest presence of Fusarium secondary metabolites. These results show that durum wheat cultivated in Northern Italy may be subject to a higher FHB infection risk and to Fusarium mycotoxins accumulation.

Durum wheat samples harvested in central Italy (Umbria) were analyzed to: evaluate the occurrence of the fungal community in the grains, molecularly identify the Fusarium spp. which are part of the Fusarium head blight (FHB) complex and characterize the in vitro secondary metabolite profiles of a subset of Fusarium strains. The Fusarium genus was one of the main components of the durum wheat fungal community. The FHB complex was composed of eight species: Fusarium avenaceum (61%), F. graminearum (22%), F. poae (9%), F. culmorum (4%), F. proliferatum (2%), F. sporotrichioides (1%), F. sambucinum (0.5%) and F. langsethiae (0.5%). F. graminearum population was mainly composed of the 15-acetyldeoxynivalenol chemotype, while, F. culmorum population was composed of the 3-acetyldeoxynivalenol chemotype. In vitro characterization of secondary metabolite biosynthesis was conducted for a wide spectrum of substances, showing the mycotoxigenic potential of the species complex. F. avenaceum strains were characterized by high enniantin and moniliformin production. F. graminearum strains were in prevalence deoxynivalenol producers. F. poae strains were characterized by a high biosynthesis of beauvericin like the F. sporotrichioides strain which was also found to be a high T-2/HT-2 toxins producer. Production of aurofusarin, butenolide, gibepyrone D, fusarin C, apicidin was also reported for the analyzed strains.

In recent years, due to the negative impact of toxigenic mycobiota and of the accumulation of their secondary metabolites in malting barley grains, monitoring the evolution of fungal communities in a certain cultivation area as well as detecting the different mycotoxins present in the raw material prior to malting and brewing processes have become increasingly important. In this study, a survey was carried out on malting barley samples collected after their harvest in the Umbria region (central Italy). Samples were analyzed to determine the composition of the fungal community, to identify the isolated Fusarium species, to quantify fungal secondary metabolites in the grains and to characterize the in vitro mycotoxigenic profile of a subset of the isolated Fusarium strains. The fungal community of barley grains was mainly composed of microorganisms belonging to the genus Alternaria (77%), followed by those belonging to the genus Fusarium (27%). The Fusarium head blight (FHB) complex was represented by nine species with the predominance of Fusarium poae (37%), followed by Fusarium avenaceum (23%), Fusarium graminearum (22%) and Fusarium tricinctum (7%). Secondary metabolites biosynthesized by Alternaria and Fusarium species were present in the analyzed grains. Among those biosynthesized by Fusarium species, nivalenol and enniatins were the most prevalent ones. Type A trichothecenes (T-2 and HT-2 toxins) as well as beauvericin were also present with a high incidence. Conversely, the number of samples contaminated with deoxynivalenol was low. Conjugated forms, such as deoxynivalenol-3-glucoside and HT-2-glucoside, were detected for the first time in malting barley grains cultivated in the surveyed area. In addition, strains of F. avenaceum and F. tricinctum showed the ability to biosynthesize in vitro high concentrations of enniatins. The analysis of fungal secondary metabolites, both in the grains and in vitro, revealed also the presence of other compounds, for which further investigations will be required. The combination of microbiological analyses, of molecular biology assays and of multi-mycotoxin screening shed light on the complexity of the fungal community and its secondary metabolites released in malting barley.